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Background: The residual life of a patient with human immunodeficiency virus (HIV) is of major interest to patients and their physicians. While existing analyses of HIV patient survival focus mostly on data collected at baseline, residual life analysis allows for dynamic analysis based on additional data collected over a period of time. As survival times typically exhibit a right-skewed distribution, the median provides a more useful summary of the underlying distribution than the mean. In this paper, we propose an efficient inference procedure that fits a semiparametric quantile regression model assessing the effect of longitudinal biomarkers on the residual life of HIV patients until the development of dyslipidemia, a disease becoming more prevalent among those with HIV. Methods: For estimation of model parameters, we propose an induced smoothing method that smooths nonsmooth estimating functions based on check functions. For variance estimation, we propose an efficient resampling-based estimator. The proposed estimators are theoretically justified. Simulation studies are used to evaluate their finite sample performances, including their prediction accuracy. We analyze the Korea HIV/AIDS cohort study data to examine the effects of CD4 (cluster of differentiation 4) cell count on the residual life of HIV patients to the onset of dyslipidemia. Results: The proposed estimator is shown to be consistent and normally distributed asymptotically. Under various simulation settings, our estimates are approximately unbiased. Their variances estimates are close to the empirical variances and their computational efficiency is superior to that of the nonsmooth counterparts. Two measures of prediction performance indicate that our method adequately reflects the dynamic character of longitudinal biomarkers and residual life. The analysis of the Korea HIV/AIDS cohort study data shows that CD4 cell count is positively associated with residual life to the onset of dyslipidemia but the effect is not statistically significant. Conclusions: Our method enables direct prediction of residual lifetimes with a dynamic feature that accommodates data accumulated at different times. Our estimator significantly improves computational efficiency in variance estimation compared to the existing nonsmooth estimator. Analysis of the HIV/AIDS cohort study data reveals dynamic effects of CD4 cell count on the residual life to the onset of dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model.Methods: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data.Results: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84).Conclusions: In this paper we have shown that the "current value" association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes. [ABSTRACT FROM AUTHOR]

Background: The benefit of a given treatment can be evaluated via a randomized clinical trial design. However, protocol deviations may severely compromise treatment effect since such deviations often lead to missing values. The assumption that methods of analysis can account for the missing data cannot be justified and hence methods of analysis based on plausible assumptions should be used. An alternative analysis to the simple imputation methods requires unverifiable assumptions about the missing data. Therefore sensitivity analysis should be performed to investigate the robustness of statistical inferences to alternative assumptions about the missing data., Aims: In this paper, we investigate the effect of tuberculosis pericarditis treatment (prednisolone) on CD4 count changes over time and draw inferences in the presence of missing data. The data come from a multicentre clinical trial (the IMPI trial)., Methods: We investigate the effect of prednisolone on CD4 count changes by adjusting for baseline and time-dependent covariates in the fitted model. To draw inferences in the presence of missing data, we investigate sensitivity of statistical inferences to missing data assumptions using the pattern-mixture model with multiple imputation (PM-MI) approach. We also performed simulation experiment to evaluate the performance of the imputation approaches., Results: Our results showed that the prednisolone treatment has no significant effect on CD4 count changes over time and that the prednisolone treatment does not interact with time and anti-retroviral therapy (ART). Also, patients' CD4 count levels significantly increase over the study period and patients on ART treatment have higher CD4 count levels compared with those not on ART. The results also showed that older patients had lower CD4 count levels compared with younger patients, and parameter estimates under the MAR assumption are robust to NMAR assumptions., Conclusions: Since the parameter estimates under the MAR analysis are robust to NMAR analyses, the process that generated the missing data in the CD4 count measurements is missing at random (MAR). The implication is that valid inferences can be obtained using either the likelihood-based methods or multiple imputation approaches.

Background: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed.Methods: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests.Results: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78).Conclusions: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population.Trial Registration: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ). [ABSTRACT FROM AUTHOR]

Background: Malawi introduced an ambitious public health program known as "Option B+" which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care. Methods/design: PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial. Results: Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17-51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75-100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22-31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24-32 months). Conclusion: The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline. Trial registration: This study is registered at clinicaltrials.gov - ID Number NCT02005835. Registered 4 December, 2013. [ABSTRACT FROM AUTHOR]

Background: Routine laboratory monitoring is part of the basic care package offered to people living with the Human Immunodeficiency Virus (PLHIV). This paper aims to identify the proportion of PLHIVs with clinical and immunological failure who are virologically suppressed and risk being misclassified as treatment failures.Methods: A retrospective analysis of patient viral load data collected between January 2013 and June 2014 was conducted. Of the patients classified as experiencing either clinical or immunological failure, we evaluated the proportion of true (virological) failure, and estimated the sensitivity and specificity of the immunological and clinical criteria in diagnosing true treatment failure.Results: Of the 27,418 PLHIVs aged 2-80 years on ART in the study period, 6.8% (n = 1859) were suspected of treatment failure and their viral loads analysed. 40% (n = 737) demonstrated viral suppression (VL < 1000 copies/ml). The median viral load (VL) was 3317 copies/ml (IQR 0-47,547). Among the 799 (2.9%) PLHIVs on ART classified as having clinical failure, 41.1% (n = 328) of them had confirmed viral suppression. Of the 463 (1.7%) classified as having immunological failure, 36.9% (n = 171) had confirmed viral suppression. The sensitivity of the clinical criteria in diagnosing true failure was 61% (CI 58%-65%) while that of the immunological criteria 38% (CI 35%-42%). The specificity of the clinical criteria was 34% (CI 30%-39%) while that of the immunological criteria 66% (61%-70%). Age below 20 years was associated with a high viral load (p < .001). Sex and ART regimen were not associated with the viral load.Conclusion: Clinical and immunological criteria alone are not sufficient to identify true treatment failure. There is need for accurate treatment failure diagnosis through viral load testing to avoid incorrect early or delayed switching of patients to second-line regimens. This study recommends increased viral load testing in line with the Kenya's ART guidelines. [ABSTRACT FROM AUTHOR]

Purposes: The aim of this study was to determine the effects of nutritional status at the start of highly active anti-retroviral therapy on treatment outcomes among HIV/AIDS patients taking HAART at Jimma University Specialized Hospital. Methods: We performed a retrospective cohort study involving 340 adults who started highly active anti-retroviral therapy. The patients have been clinically followed for 2 years. Data were extracted from paper based medical charts by trained data collectors from January 30 to February 28, 2014 using data collection format. We entered data into Epi data version 3.1 and then exported to SPSS for windows version 21. Predictors of CD4 change were identified using multivariable linear regression model. Time to an event (death) was estimated by Kaplan--Meier and predictors of mortality were identified by Cox proportional hazard model. Results: Out of 340 patients, 42 patients died during the follow-up. Twenty-five (59.5 %) deaths were from malnourished group. Age, baseline CD4, sex, baseline HAART and marital status were significant predictors of immunologic recovery at different time points. Malnutrition was associated with lower CD4 recovery and greater hazard of death. Conclusions: Malnutrition tends to decrease CD4 recovery and predisposes patient to early death. [ABSTRACT FROM AUTHOR]

Background: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. Methods: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/μl after 24 months' treatment), immunological incomplete responders (ICRs) (200–350 cells/μl) and INRs (< 200 cells/μl). Multivariable logistic regression was used to assess factors associated with immunological non-response. Results: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39–3.09), older age [40–49 years (vs. 18–29 years): 2.05, 1.29–3.25; 50–59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84–10.67], HBV co-infection (1.63, 1.14–2.34), HCV co-infection (2.01, 1.01–4.02), lower CD4 + T cell count [50–200 cells/μl (vs. 200–350 cells/μl): 40.20, 16.83–96.01; < 50 cells/μl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98–4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26–0.82). Conclusions: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor. [ABSTRACT FROM AUTHOR]

Background: Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin resistant Staphylococcus aureus among HIV-infected patients. Recurrent infections are frequent. Risk factors for recurrence after an initial SSTI have not been well-studied.Methods: Retrospective cohort study, single center, 2005-2009. Paper and electronic medical records were reviewed by one of several physicians. Subjects with initial SSTI were followed until the time of SSTI recurrence. Standard descriptive statistics were calculated to describe the characteristics of subjects who did and did not develop a recurrent SSTI. Kaplan-Meier methods were used to estimate the risk of recurrent SSTI. A Cox regression model was developed to identify predictors of SSTI recurrence.Results: 133 SSTIs occurred in 87 individuals. 85 subjects were followed after their initial SSTI, of whom 30 (35.3 %) had a recurrent SSTI in 118.3 person-years of follow-up, for an incidence of second SSTI of 253.6 SSTIs/1000 person-years (95 % CI 166.8-385.7). The 1-year Kaplan-Meier estimated risk of a second SSTI was 29.2 % (95 % CI 20.3-41.0 %), while the 3-year risk was 47.0 % (95 % CI 34.4-61.6 %). Risk factors for recurrent SSTI in a multivariable Cox regression model were non-hepatitis liver disease (HR 3.44; 95 % CI 1.02-11.5; p = 0.05), the presence of an intravenous catheter (HR 6.50; 95 % CI 1.47-28.7; p = 0.01), and a history of intravenous drug use (IVDU) (HR 2.80; 95 % CI 1.02-7.65; p = 0.05); African-American race was associated with decreased risk of recurrent SSTI (HR 0.12; 95 % CI 0.04-0.41; p < 0.01). Some evidence was present for HIV viral load ≥ 1000 copies/mL as an independent risk factor for recurrent SSTI (HR 2.21; 95 % CI 0.99-4.94; p = 0.05). Hemodialysis, currently taking HAART, CD4+ count, trimethoprim-sulfamethoxazole or azithromycin use, initial SSTI type, diabetes mellitus, incision and drainage of the original SSTI, or self-report of being a man who has sex with men were not associated with recurrence.Conclusion: Of HIV-infected patients with an SSTI, nearly 1/3 had a recurrent SSTI within 1 year. Risk factors for recurrent SSTI were non-hepatitis liver disease, intravenous catheter presence, a history of IVDU, and non-African-American race. Low CD4+ count was not a significant risk factor for recurrence. [ABSTRACT FROM AUTHOR]

Background: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts.Methods: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3.Results: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance.Conclusions: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa. Methods: A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I2 heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger's regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR). Results: Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88–4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61–1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13–1.35), male gender (AHR = 1.43, 95% CI: 1.22–1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34–3.23), anemia (AHR = 1.73, 95% CI: 1.34–2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08–2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08–2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3–0.77). Conclusion: In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people. [ABSTRACT FROM AUTHOR]

Background: Despite increasing effort for treating primary central nervous system lymphoma (PCNSL), the prognosis of human immunodeficiency virus (HIV) -related PCNSL was still unsatisfactory. There is currently a lack of clinical evidence for the application of Bruton tyrosine kinase (BTK) inhibitor in HIV-related PCNSL. We reported two HIV-related PCNSL patients, who achieved sustained remission by application of BTK inhibitor based treatment. This protocol had not been previously reported for the treatment of HIV-related PCNSL. Case presentation: The two cases were characterized by the treatment choice of Bruton tyrosine kinase (BTK) inhibitor. Rituximab was not recommended for them due to their very low CD4+ T cell counts. They both took MTX as the first-line therapy and got a relief in initial phase. For the first case, ibrutinib was kept both in the first-line therapy and in the maintenance therapy. When the second case underwent a progressive disease, we continued to use orelabrutinib as one of the salvage treatment, in combination with programmed cell death-1 (PD-1) inhibitor plus lenalidomide. They both achieved a continuous response of up to 20 months without opportunistic infection. Conclusions: This report highlights the safety and effectiveness of BTK inhibitors, as well as lenalidomide and PD-1 inhibitor in HIV-related PCNSL patients. Both the new therapeutic approaches and a multidisciplinary team authentically contributed to improved survival outcome among HIV-positive PCNSL patients. [ABSTRACT FROM AUTHOR]

Background: In 2003, China implemented free antiretroviral therapy (ART) for people living with HIV (PLHIV), establishing an eligibility threshold of CD4 < 200 cells/μl. Subsequently, the entry criteria were revised in 2012 (eligibility threshold: CD4 ≤ 350 cells/μl), 2014 (CD4 ≤ 500 cells/μl), and 2016 (treat-all). However, the impact of treat-all policy on HIV care and treatment indicators in China is unknown. We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China. Methods: Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019, from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China. We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators: monthly proportion of 30-day ART initiation, mean CD4 counts (cells/μl) at ART initiation, and mean estimated time from infection to diagnosis (year). We built separate models according to gender, age, route of transmission and region. Results: Monthly data on ART initiation and collection were available for 75,516 individuals [gender: 83.8% males; age: median 39 years, interquartile range (IQR): 28–53; region: 18.5% Northern China, 10.9% Northeastern China, 17.5% Southern China, 49.2% Southwestern China]. In the first month of treat-all, compared with the contemporaneous counterfactual, there was a significant increase in proportion of 30-day ART initiation [+ 12.6%, incidence rate ratio (IRR) = 1.126, 95% CI: 1.033–1.229; P = 0.007] and mean estimated time from infection to diagnosis (+ 7.0%, IRR = 1.070, 95% CI: 1.021–1.120; P = 0.004), while there was no significant change in mean CD4 at ART initiation (IRR = 0.990, 95% CI: 0.956–1.026; P = 0.585). By December 2019, the three outcomes were not significantly different from expected levels. In the stratified analysis, compared with the contemporaneous counterfactual, mean CD4 at ART initiation showed significant increases in Northern China (+ 3.3%, IRR = 1.033, 95% CI: 1.001–1.065; P = 0.041) and Northeastern China (+ 8.0%, IRR = 1.080, 95% CI: 1.003–1.164; P = 0.042) in the first month of treat-all; mean estimated time from infection to diagnosis showed significant increases in male (+ 5.6%, IRR = 1.056, 95% CI: 1.010–1.104; P = 0.016), female (+ 14.8%, IRR = 1.148, 95% CI: 1.062–1.240; P < 0.001), aged 26–35 (+ 5.3%, IRR = 1.053, 95% CI: 1.001–1.109; P = 0.048) and > 50 (+ 7.8%, IRR = 1.078, 95% CI: 1.000–1.161; P = 0.046), heterosexual transmission (+ 12.4%, IRR = 1.124, 95% CI: 1.042–1.213; P = 0.002) and Southwestern China (+ 12.9%, IRR = 1.129, 95% CI: 1.055–1.208; P < 0.001) in the first month of treat-all. Conclusions: The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes. To advance the work of rapid ART, efforts should be made to streamline the testing and ART initiation process, provide comprehensive support services, and address the issue of uneven distribution of medical resources. [ABSTRACT FROM AUTHOR]

Background: The serum systemic inflammation biomarkers have been established as predictors of prognosis in gastric cancer (GC) patients, but their prognostic value in human immunodeficiency virus (HIV)-infected patients with GC has not been well studied. This retrospective study aimed to evaluate the prognostic value of preoperative systemic inflammation biomarkers in Asian HIV-infected patients with GC. Methods: We retrospectively analyzed 41 HIV-infected GC patients who underwent surgery between January 2015 and December 2021 at the Shanghai Public Health Clinical Center. Preoperative systemic inflammation biomarkers were measured and patients were divided into two groups based on the optimal cut-off value. Overall survival (OS) and progression-free survival (PFS) were measured using the Kaplan–Meier method and the log-rank test. Multivariate analysis of variables was performed using the Cox proportional regression model. As a comparison, 127 GC patients without HIV infection were also recruited. Results: The median age of the 41 patients included in the study was 59 years, with 39 males and two females. The follow-up period for OS and PFS ranged from 3 to 94 months. The cumulative three-year OS rate was 46.0%, and the cumulative three-year PFS rate was 44%. HIV-infected GC patients had worse clinical outcomes compared to the normal GC population. The optimal cut-off value for preoperative platelet to lymphocyte ratio (PLR) was 199 in HIV-infected GC patients. Multivariate Cox regression analysis revealed that a low PLR was an independent predictor of better OS and PFS (OS: HR = 0.038, 95% CI: 0.006–0.258, P < 0.001; PFS: HR = 0.027, 95% CI: 0.004–0.201, P < 0.001). Furthermore, higher preoperative PLR in HIV-infected GC was significantly associated with lower BMI, hemoglobin, albumin, CD4 + T, CD8 + T, and CD3 + T cell counts. Conclusion: The preoperative PLR is an easily measurable immune biomarker that may provide useful prognostic information in HIV-infected GC patients. Our findings suggest that PLR could be a valuable clinical tool for guiding treatment decisions in this population. [ABSTRACT FROM AUTHOR]

Background: Dropout is a common problem in longitudinal clinical trials and cohort studies, and is of particular concern when dropout occurs for reasons that may be related to the outcome of interest. This paper reviews common parametric models to account for dropout and introduces a Bayesian semi-parametric varying coefficient model for exponential family longitudinal data with non-ignorable dropout.Methods: To demonstrate these methods, we present results from a simulation study and estimate the impact of drug use on longitudinal CD4 + T cell count and viral load suppression in the Women's Interagency HIV Study. Sensitivity analyses are performed to consider the impact of model assumptions on inference. We compare results between our semi-parametric method and parametric models to account for dropout, including the conditional linear model and a parametric frailty model. We also compare results to analyses that fail to account for dropout.Results: In simulation studies, we show that semi-parametric methods reduce bias and mean squared error when parametric model assumptions are violated. In analyses of the Women's Interagency HIV Study data, we find important differences in estimates of changes in CD4 + T cell count over time in untreated subjects that report drug use between different models used to account for dropout. We find steeper declines over time using our semi-parametric model, which makes fewer assumptions, compared to parametric models. Failing to account for dropout or to meet parametric assumptions of models to account for dropout could lead to underestimation of the impact of hard drug use on CD4 + cell count decline in untreated subjects. In analyses of subjects that initiated highly active anti-retroviral treatment, we find that the estimated probability of viral load suppression is lower in models that account for dropout.Conclusions: Non-ignorable dropout is an important consideration when analyzing data from longitudinal clinical trials and cohort studies. While methods that account for non-ignorable dropout must make some unavoidable assumptions that cannot be verified from the observed data, many methods make additional parametric assumptions. If these assumptions are not met, inferences can be biased, making more flexible methods with minimal assumptions important. [ABSTRACT FROM AUTHOR]

Historically, COVID-19 emerges as one of the most devastating diseases of humankind, which creates an unmanageable health crisis worldwide. Until now, this disease costs millions of lives and continues to paralyze human civilization's economy and social growth, leaving an enduring damage that will take an exceptionally long time to repair. While a majority of infected patients survive after mild to moderate reactions after two to six weeks, a growing population of patients suffers for months with severe and prolonged symptoms of fatigue, depression, and anxiety. These patients are no less than 10% of total COVID-19 infected individuals with distinctive chronic clinical symptomatology, collectively termed post-acute sequelae of COVID-19 (PASC) or more commonly long-haul COVID. Interestingly, Long-haul COVID and many debilitating viral diseases display a similar range of clinical symptoms of muscle fatigue, dizziness, depression, and chronic inflammation. In our current hypothesis-driven review article, we attempt to discuss the molecular mechanism of muscle fatigue in long-haul COVID, and other viral diseases as caused by HHV6, Powassan, Epstein–Barr virus (EBV), and HIV. We also discuss the pathological resemblance of virus-triggered muscle fatigue with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). [ABSTRACT FROM AUTHOR]

Objectives: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. Methods: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). Results: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38–51), who had been on ART for a median of 7 years (IQR 4–13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4–86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64–8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. Conclusion: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure. [ABSTRACT FROM AUTHOR]

Introduction: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. Methods: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. Results: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. Conclusions: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis. [ABSTRACT FROM AUTHOR]

Background: Adherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers. However, to date, the approved LAI-ART strategies (e.g., cabotegravir and rilpivirine (CAB/RPV)) have targeted those who have already attained viral suppression, precluding their use in the 40% of adolescents and young adults (AYA) that VS has eluded. Case presentation: Ms. X is a 30-year-old woman with perinatally-acquired HIV and barriers to adherence. Despite many interventions, she remained persistently viremic, with resultant immune suppression and multiple comorbid opportunistic conditions, and viral load (VL) > 10,000,000 copies/ml. Given her longstanding history of poor adherence to an oral regimen, a switch to monthly intramuscular (IM) injections and biweekly infusions of ibalizumab were initiated leading to decreased viral load to 8,110 copies/ml within two weeks. Ms. H is a 33-year-old woman with cognitive limitations due to childhood lead poisoning. Her viral load trajectory took a downward turn, precipitated by various life events, remaining elevated despite intensive case management. Initiation of LAI-ART (CAB/RPV) in this patient led to an undetectable VL (< 20 copies/ml) within two months of treatment initiation. Miss Y. is a 37-year-old woman with perinatally-acquired HIV and chronic challenges with nonadherence and longstanding immunosuppression with CD4 < 200 cells/mm3 for > 5 years. She received a 1-month oral lead-in (OLI) of cabotegravir/rilpivirine, followed by the injectable loading dose. She has since adhered to all her monthly dosing appointments, sustained VS, and transitioned to a bi-monthly injection schedule. Conclusion: These three individuals with HIV (perinatally and non-perinatally acquired) with longstanding nonadherence and persistent viremia were successfully initiated on LAI-ART through the process of care coordination and the collective efforts of the care team, highlighting the barriers, challenges, and the multidisciplinary coordination needed to assure successful implementation of this strategy for the most vulnerable of patients. [ABSTRACT FROM AUTHOR]

Background: Mother to child human immune virus (HIV) transmission is the passage of HIV from mother to her child during pregnancy, labor, delivery or breast-feeding. The objective of this study was to identify determinants of mother to child HIV transmission among HIV exposed infants who were born from HIV positive mothers at Governmental health centers of East Gojjam Zone, Northwestern Ethiopia, 2019. Methods: A case–control study was conducted on 210(42 cases and 168 controls) from April 1 to 30/ 2019. All cases were included in the study. Controls were selected by simple random sampling. Secondary data were extracted by using checklists from the document of 8 health centers ART register book, antenatal care (ANC) follow up register book, PMTCT service registration log book charts and infant dried blood sample (DBS) tally sheets. After Bivariable logistic regression analysis, all variables with p-value ≤ 0.25 were entered into multivariable logistic regression and p value < 0.05 considered as significantly associated with the outcome variable. Results: HIV exposed infants who were being rural dweller versus (vs) those infants who were being urban dweller [adjusted odds ratio (AOR) = 3.73; 95% CI; 1.27–10.69], have no history of antenatal care follow up of HIV exposed infants' HIV positive mothers versus (vs) those mothers who have been having history of ANC follow up [ AOR = 5.0;95%CI; 2.02–12.16] and initial CD4 count of HIV infants' mothers ≤ 350 vs those mothers whose CD4 > 350 [AOR = 2.7;95%CI;1.35–5.52] were significantly associated with HIV infection. Conclusion: Mother to child HIV transmission was significantly associated with history of ANC follow up of exposed infants' mothers and initial CD4 counts of mothers. Strong effort should be made to further increase the ANC service utilization of HIV positive pregnant women. Plain English summary: Prevention of Mother to child human immune virus (HIV) transmission is the primary method of infection among children. To eliminate infection in children and keep mothers alive, a comprehensive package of interventions accelerating, including preventing of women from becoming infected with HIV, protect unwanted pregnancy, throughout pregnancy, provide skilled delivery, exclusive breastfeeding and providing appropriate HIV treatment, care, and support for mother and infants. Despite the availability and scale-up of life-saving interventions, only a few pregnant women living with HIV in Ethiopia have been receiving the medication to prevent mother to child HIV transmission. There is limited information about determinant of mother to child HIV transmission in Ethiopia. In this study, the data were extracted from the document of health centers ART register book, ANC follow up register book, PMTCT service registration log book charts and infant DBS tally sheets in East Gojjam, Ethiopia. This study revealed that high proportion of HIV infection among exposed infants in the study area. Infections with HIV among HIV exposed infants were positively associated with history of ANC follow up of their mothers and initial CD4 counts of their mothers. [ABSTRACT FROM AUTHOR]

Background: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV (PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. Methods: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine (Sinopharm, WIBP-CorV, Wuhan Institute of Biological Products Co. Ltd) at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7 days after each injection. The primary immunogenicity outcomes were SARS-CoV-2 neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70. Results: In total, the study included 46 PLWH and 38 HNC who finished 70 days' follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs. HNC (32% and 24%). NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI 3.18–5.87) and 26% (95% CI 14–41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI 10.33–32.33), seroconversion rate (63%, 95% CI 44–79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI 0.119–0.313) and 51% (95% CI 34–69), which was lower than that among HNC [GMEU (0.379 EU/mL, 95% CI 0.224–0.653), seroconversion rate (86%, 95% CI 64–97)]. There were no serious adverse events. Conclusions: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count with effective antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment).Methods: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time.Results: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status.Conclusions: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis (CM) and tuberculosis (TB) remain leading causes of hospitalization and death amongst people living with HIV, particularly those with advanced HIV disease. In hospitalized patients, prompt diagnosis of these diseases may improve patient outcomes. The advanced HIV rapid diagnostic tests such as determine TB urine lipoarabinomannan lateral flow assay (urine LAM), urine X-pert MTB/RIF assay (urine X-pert), and serum/blood cryptococcal antigen test (serum CrAg) are recommended but frequently not available in many resource-limited settings. We describe our experience providing these tests in a routine hospital setting.Method: From 1 August 2016 to 31 January 2017, a prospective cohort study to diagnose TB and Cryptococcal meningitis using point of care tests was conducted in the medical wards at Kamuzu Central Hospital, in Lilongwe, Malawi. The tests offered were PIMA CD4 cell count, serum CrAg, urine LAM, and urine X-pert. The testing was integrated into an existing HIV/TB treatment room on the wards and performed close to admission time. Patients were followed until discharge or death in the ward.Results: We included 438 HIV-positive patients; 76% had a previously known HIV diagnosis (87% already on ART). We measured CD4 count in 365/438 (83%), serum CrAg in 301/438 (69%), urine LAM in 363/438 (83%), and urine X-pert in 292/438 (67%). The median CD4 count was 144 cells/ml (IQR 46-307). Serum CrAg positivity rate was 23 /301 (8%) and CM was confirmed by CSF Crag in 13/23 (56%). The majority of CM patients 9/13 (69%) started antifungal therapy within two days of diagnosis. Urine LAM and urine X-pert positivity rates were 81/363(22%) and (14/292 (5%) respectively. The positivity rate of urine LAM was higher in patients with low CD4 cell counts (< 100 cells/ml) and low BMI (< 18.5). Most patients with positive urine LAM started TB treatment on the same day. Despite the early diagnosis and treatment of TB and CM, the inpatient mortality was high; 30% and 25% respectively.Conclusion: Although advanced HIV rapid diagnostic tests are recommended, one key challenge in implementation is the limited trained personnel administering the tests. Despite the effective use of the point of care tests in the clinical care of hospitalized TB and CM patients, mortality among these patients remained unacceptably high. Henceforth we need to train other cadres apart from nurses, clinicians, and laboratory technicians to conduct the tests. There is an urgent need to identify and modify other risks of death from TB and CM.Trial Registration: Malawi National Health Science Research committee: Protocol # 1144. Registered 2 July 2014 and University Of North Carolina IRB #: UNCPM 21412, approved 13th October 2014. [ABSTRACT FROM AUTHOR]

Background: Poor antiretroviral therapy (ART) adherence is a challenge to containing the spread of HIV. This is an especially difficult challenge in conflict and post-conflict settings. This study investigates the relationship between attendance in an Orphan and Vulnerable Children program in South Sudan and HIV-related outcomes, including clinic appointment attendance, frequency of viral load testing and viral load suppression rates.Methods: Patient records (n = 295) were selected from project-supported clinics in Juba, South Sudan, and analyzed to measure the association between enrollment status and select health outcomes. Data were collected at multiple time points between 2018 and 2019, to measure the strength of relationship between select treatment variables (e.g., viral load, retention in care, etc.). Given the structure of the data, non-parametric tests were applied to answer the research questions.Results: Analysis revealed three important trends: (1) enrollment in the 4Children project was associated with a statistically significant increase in the frequency of viral load testing; (2) there was an increase in median appointment attendance after program enrollment; and (3) there was improved management of viral load and CD4 count, albeit small, during the time period before and after enrollment.Conclusions: Data from South Sudan suggests that caregivers and children receiving project services saw improvement in treatment-related indicators. After enrolling in the project, overall amount of viral load testing increased from previous counts before enrollment. This suggests that after providing additional services with psychosocial and financial support to patients at the two hospitals in Juba, there was potential that similar interventions can support improved HIV outcomes. [ABSTRACT FROM AUTHOR]

Background: Anti-retroviral therapy regimen discontinuations become a big challenge and cause diminishing the clinical and immunological benefit of treatment in Ethiopia. It reduces both the duration and the chance of viral control due to cross-resistance between different alternative drugs and overlapping toxicity between and within a class of antiretroviral drugs in Ethiopia. However, information's on the time of initial regimen discontinuation and its predictors are not well studied. Objective: This study aimed to assess the time to initial highly active antiretroviral therapy discontinuation and its predictors among HIV patients in Felege Hiwot comprehensive specialized hospital, North West Ethiopia. Method: Institution-based retrospective cohort study was conducted among 418 HIV patients who started HAART from January 1, 2014, to December 31, 2019. Data were collected from the patient chart using a data extraction tool. The Kaplan–Meier curve was employed to compare survival rates. Multivariable Cox proportional hazard regression was applied to identify independent predictors of time to initial regimen discontinuation. Result: A total of 418 patients on anti-retroviral therapy were followed. Incidence of initial HAART discontinuation was 16.7/100 person year. The median survival time was 3.5 years. Predictors showed association for time to initial HAART discontinuation were taking > 1 ART pills/day (AHR = 4.1, 95% CI 3.0–6.5), baseline CD4 count < 100 cells/mm3 (AHR = 2.6, 95% CI 1.5–4.7), 100–199 cells/mm3 (AHR = 2.2, 95% CI 1.2–4.0), baseline WHO clinical stage IV (AHR = 2.68, 95% CI 1.6–4.3) and stage III (AHR = 2.6, 95% CI 1.4–4.3) and TB infection (AHR = 2.3, 95% CI 1.6–3.5). Conclusion: Most of the discontinuation occurred after 1 year of initiation of HAART. Baseline WHO clinical stage, TB infection, baseline CD4 count, and taking > 1 ART pill/day were found predictors of initial HAART regimen discontinuation. Work on early detection of HIV before the disease is advanced and initiation of one ART regimen daily is vital for survival on the initial regimen. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is very common in HIV-infected individuals. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of the nutritional status of HIV-infected children. Hence, this study aims to assess the nutritional status and associated factors among children on antiretroviral therapy. Methods: An institutional-based cross-sectional study was conducted among 383 HIV-positive children in Southern Ethiopia. Data were collected using an interviewer-administered questionnaire and anthropometry measurement. Data were coded and entered into Epi-Data Version 3.1 and analyzed using SPSS Version 25. Bi-variable and multi-variable binary logistic regression models were used to identify factors associated with nutritional status and variables with p-values <0.05 in multi-variable logistic regression were considered as statistically significant. Results: The prevalence of wasting among HIV-positive children in Southern Ethiopiaselected Hospitals was 36.3% (95% CI, 31.6–41.0) while stunting on the same study population was 5.5% (95% CI, 3.4–7.8). Rural residence, lack of maternal education, low CD4 counts (< 500), using an unprotected water source, having a non-biological mother and recurrent oral lesion were significantly associated with wasting. Furthermore, history of hospital admission, recurrent oral lesion, low CD4 counts (< 500), advanced WHO clinical stage were statically associated with stunting with p-value < 0.05. Conclusion: This study found that the prevalence of under-nutrition among HIV-positive children in Ethiopia was significantly high. Therefore, timely identification and monitoring of nutritional problems should be necessary to enhance the effectiveness of ART treatment and to prevent further related complications. [ABSTRACT FROM AUTHOR]

Objective: CD4 Lymphocyte Count (CD4) is a major predictor of HIV progression to AIDS. Exploring the factors affecting CD4 levels may assist healthcare staff and patients in management and monitoring of health cares. This retrospective cohort study aimed to explore factors associated with CD4 cell counts at the time of diagnosis in HIV patients using Poisson, Generalized Poisson, and Negative Binomial regression models. Results: Out of 4402 HIV patients diagnosis in Iran from 1987 to 2016, 3030 (68.8%) were males, and the mean age was 34.8 ± 10.4 years. The results indicate that the Negative Binomial model outperformed the other models in terms of AIC, log-likelihood and RMSE criteria. In this model, factors include sex, age, clinical stage and Tuberculosis (TB) co-infection were significantly associated with CD4 count (P < 0.05). Conclusion: Given the effect of age, sex, clinical stage and stage of HIV on CD4 count of the patients, adopting policies and strategies to increase awareness and encourage people to seek early HIV testing and care is advantageous. [ABSTRACT FROM AUTHOR]

Background: HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART.Methods: From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool.Results: The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013).Conclusions: The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus attacked an immune cell and the CD4 cell which is responsible for the body's immune to infectious agents. Acquired immunodeficiency syndrome is one of the major public health problems in Sub-Saharan Africa including Ethiopia. The main objective of this study to identify the determinants of CD4 cell count among antiretroviral therapy attendants of infected adults follow up in Gonder teaching referral hospital, Gonder, Ethiopia implemented by SAS version 94. Methods: A retrospective cohort study was conducted on 216 regular follow up patients whose age greater than 14 years from December 1, 2012, to December 30, 2017. A multilevel model was used to identify the factors of CD4 cell count of patients and it considered variability between and within patients. Results: The mean with a standard deviation of weight, and a hemoglobin level of patients were 55.48 (10.21), and 18.25 (33.028) respectively. This study concluded that the variation for CD4 cell count existed between patients was 63% and the remaining 37% of variation existing within patients. In this study, the random coefficient time-varying covariate model was well fitted which shows weight and hemoglobin level were statistically significant predictors at a 5% level of significance for the log of CD4 cell count of patients. Conclusion: This study shows the hemoglobin level and weight of patients were statistically significant for the log of CD4 cell count of patients follow up in Gonder teaching referral hospital, Gonder, Ethiopia. Moreover, the result of the study shows that the log of CD4 count of patients increased when hemoglobin level and weight of patients increased. Hence, intervention should be given the ways to increase weight and hemoglobin levels of patients during follow up of antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background: Self-reported antiretroviral therapy (ART) adherence measures that are associated with plasma viral load (VL) are valuable to clinicians and researchers, but are rarely examined among groups vulnerable to dropping out of care. One-seventh of all those living with HIV pass through incarceration annually and criminal-justice (CJ) involved people living with HIV (PLH) are vulnerable to falling out of care. We examined the association of self-reported ART adherence with VL in a criminal-justice sample compared to a routine-care sample.Methods: Samples: We examined data from a multisite collaboration of studies addressing the continuum of HIV care among CjJ involved persons in the Seek, Test, Treat, and Retain cohort. Data pooled from seven CJ- studies (n = 414) were examined and compared with the routine-care sample from the Centers for AIDS Research Network of Integrated Clinical Systems' seven sites (n = 11,698).Measures: In both samples, data on self-reported percent ART doses taken were collected via the visual analogue scale adherence measure. Viral load data were obtained by blood-draw.Analysis: We examined the associations of adherence with VL in both cohorts using mixed effects linear regression of log-VL, and mixed effects logistic regression of binary VL (≥ 200 copies/mL) outcomes. Interactions by CD4 count and self-reported health status were also tested.Results: Among the CJ sample, the coefficient for log-VL was - 0.31 (95% CI = - 0.43, - 0.18; P < 0.01) and that in the routine-care sample was - 0.42 (95% CI = - 0.45, - 0.38; P < 0.01). For the logistic regression of binary detectable VL on 10% increments of adherence we found the coefficient was - 0.26 (95% CI = - 0.37, - 0.14; P < 0.01) and in the routine-care sample it was - 0.38 (95% CI = - 0.41, - 0.35; P < 0.01). There was no significant interaction by CD4 count level in the CJ sample, but there was in the routine-care sample. Conversely, there was a significant interaction by self-reported health status level in the criminal-justice sample, but not in the routine-care sample.Conclusions: The visual analogue scale is valid and useful to measure ART adherence, supporting treatment for CJ- involved PLH vulnerable to falling out of care. Research should examine adherence and VL in additional populations. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up after a positive infant HIV diagnosis negates the potential benefits of robust policies recommending immediate triple antiretroviral therapy initiation in HIV positive infants. Whilst the diagnosis and follow-up of HIV positive infants in urban, specialized settings is easier to institutionalize, there is little information about access to care amongst HIV positive children diagnosed at primary health care clinic level. We sought to understand the characteristics of HIV positive children diagnosed with HIV infection at primary health care level, across all provinces of South Africa, their attendance at study-specific exit interviews and their reported uptake of HIV-related care. The latter could serve as a marker of knowledge, access or disclosure.Methods: Secondary analysis of data gathered about HIV positive children, participating in an HIV-exposed infant national observational cohort study between October 2012 and September 2014, was undertaken. HIV infected children were identified by total nucleic acid polymerase chain reaction using standardized procedures in a nationally accredited central laboratory. Descriptive analyses were conducted on the HIV positive infant population, who were treated as a case series in this analysis. Data from interviews conducted at baseline (six-weeks post-delivery) and on study exit (the first visit following infant HIV positive diagnosis) were analysed.Results: Of the 2878 HIV exposed infants identified at 6 weeks, 1803 (62.2%), 1709, 1673, 1660, 1680 and 1794 were see at 3, 6, 9, 12, 15 and 18 months respectively. In total, 101 tested HIV positive (67 at 6 weeks, and 34 postnatally). Most (76%) HIV positive infants were born to single mothers with a mean age of 26 years and an education level above grade 7 (76%). Although only 33.7% of pregnancies were planned, 83% of mothers reported receiving antiretroviral drugs to prevent MTCT. Of the 44 mothers with a documented recent CD4 cell count, the median was 346.8 cell/mm3. Four mothers (4.0%) self-reported having had TB. Only 59 (58.4%) HIV positive infants returned for an exit interview after their HIV diagnosis; there were no statistically significant differences in baseline characteristics between HIV positive infants who returned for an exit interview and those who did not. Amongst HIV positive infants who returned for an exit interview, only two HIV positive infants (3.4%) were reportedly receiving triple antiretroviral therapy (ART). If we assume that all HIV positive children who did not return for their exit interview received ART, then ART uptake amongst these HIV positive children < 18 months would be 43.6%.Conclusions: Early ART uptake amongst children aged 15 months and below was low. This raises questions about timely, early paediatric ART uptake amongst HIV positive children diagnosed in primary health care settings. Qualitative work is needed to understand low and delayed paediatric ART uptake in young children, and more work is needed to measure progress with infant ART initiation at primary care level since 2014. [ABSTRACT FROM AUTHOR]

Background: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART.Methods: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at  three months and one year of follow-up.Results: 468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive - including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9-7.1) and 2.6 (95%, 1.2-5.7), respectively.Conclusions: Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to describe the prevalence, clinical presentation and risk factors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) cases in China.Methods: We performed a descriptive analysis of demographic and clinical data of HIV/TB coinfected patients receiving ART at Beijing Ditan Hospital between January 2014 and October 2018.Results: Of 199 patients included, 45 (22.6%) developed paradoxical TB-IRIS, and 19 (9.5%) TB-IRIS cases presented miliary TB. The pre-ART CD4 count lower than 50 cells/mm3 was found to be significantly associated with development of TB-IRIS. Similarly, patients with higher than 4-fold increase in CD4 cell count after antiretroviral therapy (ART) had significantly higher odds of having TB-IRIS. When patients aged 25-44 years were utilized as the control group, youths (< 25 years old) were more likely to have miliary TB. No significant difference was observed in the intervals from initiation of ART to IRIS presentation between miliary and non-miliary group.Conclusions: In conclusion, our data demonstrate that approximate one quarter of patients coinfected with TB and HIV develop paradoxical TB-IRIS after initial of ART therapy in China. Lower baseline CD4 count and rapid increase in CD4 count are the major risk factors associated with the occurrence of paradoxical TB-IRIS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of AIDS-defining events (ADE) on long-term mortality of HIV positive individuals on antiretroviral therapy (ART), a retrospective HIV/AIDS treatment cohort study performed in Southwestern China. Methods: The retrospective cohort was conducted among 6757 HIV/AIDS patients on ART (2NRTIs + 1NNRTI, 2NRTIs + 1PI and Single or two drugs) recruited in Guigang city, Guangxi, China, from January 2004 to December 2018. Participants were divided into ADE and non-ADE groups, and were followed-up every six months to observe treatment outcomes. Comparison of mortality between groups was performed using the log-rank test and Kaplan–Meier analysis. Cox proportional hazard regression was used to explore the risk factors of mortality. 1:1 propensity score matching (PSM) was used to balance confounding factors and adjust the mortality risk. Results: Of 6757 participants with 29,096.06 person-years of follow-up, 16.86% (1139/6757) belonged to ADE group while the others (83.14%) belonged to the non-ADE group. The most common cause of death by ADE was disseminated mycosis (31.65%), followed by recurrent severe bacterial pneumonia (28.48%), herpes zoster (17.72%), and extra-pulmonary tuberculosis (8.86%). The mortality of the ADE group was significantly higher than that of the non-ADE group [3.45/100 person-years (95% CI 2.92–3.97) vs. 2.34/100 person-years (95% CI 2.15–2.52), P<0.001]. The death risk of the ADE group was also higher than that of the non- ADE group [adjusted hazard ratio (aHR) = 1.291, 95% CI 1.061–1.571, P = 0.011], which was confirmed by PSM analysis (aHR = 1.581, 95% CI 1.192–2.099, P = 0.002). Cox analysis indicated that ADE, older age, male gender, previous non-use of cotrimoxazole, advanced WHO clinical stage, and low baseline CD4+ cell count were the risk factors for death. Conclusions: Even on ART, the mortality risk of HIV positive individuals with ADE was higher than those without ADE. Active testing, earlier diagnosis, and timely therapy with ART may reduce the death risk of ADE. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral treatment has played a pivotal role in the reduction of HIV/AIDS-related morbidity and mortality. However, treatment options can be impaired by the development of antiretroviral treatment failure. Regular monitoring of the Human Immunodeficiency Virus treatment outcome via viral load tests is the key approach. There is a scarcity of information about HIV treatment failure and risk factors in the study area. Therefore, the study was aimed to assess antiretroviral treatment failure and associated factors among patients on first-line antiretroviral treatment at Tefera Hailu Memorial Hospital, Sekota, northeast Ethiopia. Methods: A hospital-based cross-sectional study was conducted on 295 patients on first-line antiretroviral treatment from Nov. 2018 to Apr. 2019. Socio-demographic and clinical variables were collected using a pretested questionnaire, and blood specimen was collected for PCR viral load and CD4 + cell count estimation. Data were entered into Epi-Info and exported to SPSS for analysis. A binary logistic regression model was used to identify associated factors, and P value < 0.05 was considered as statistically significant. Results: Of the 295 subjects on first-line ART, 49 (16.6%) and 18 (6.1%) experienced virological and immunological failures, respectively. The failure of the former was associated with poor adherence (AOR: 6.367, P < 0.001), CD4 + count < 500 cells/µL (AOR: 4.78, P = 0.031) and shorter (6–24 months) duration on ART (AOR: 0.48, P = 0.048), while poor treatment adherence (AOR: 11.51, P = 0.012) and drug interruption (AOR: 6.374, P = 0.039) were the independent risk factors for latter. Immunological tests to predict virological failures showed as sensitivity, specificity, PPV, and NPV were 20.4%, 96.7%, 55.5%, and 86.0%, respectively. Conclusions: The rate of ART failure was considerably high. Poor adherence, low CD4 + count, prolonged ART, and drug interruption were found to be the most predictor variables for virological and immunological failures. The discrimination power of the immunological parameter was low in comparison to virological measurements as standard methods. Therefore, the study highlighted the need for more attention and efforts to curb associated factors and maximize virological tests for monitoring treatment failures. [ABSTRACT FROM AUTHOR]

Background: Ordinal health longitudinal response variables have distributions that make them unsuitable for many popular statistical models that assume normality. We present a multilevel growth model that may be more suitable for medical ordinal longitudinal outcomes than are statistical models that assume normality and continuous measurements.Methods: The data is from an ongoing prospective cohort study conducted amongst adult women who are HIV-infected patients in Kwazulu-Natal, South Africa. Participants were enrolled into the acute infection, then into early infection subsequently into established infection and afterward on cART. Generalized linear multilevel models were applied.Results: Multilevel ordinal non-proportional and proportional-odds growth models were presented and compared. We observed that the effects of covariates can't be assumed identical across the three cumulative logits. Our analyses also revealed that the rate of change of immune recovery of patients increased as the follow-up time increases. Patients with stable sexual partners, middle-aged, cART initiation, and higher educational levels were more likely to have better immunological stages with time. Similarly, patients having high electrolytes component scores, higher red blood cell indices scores, higher physical health scores, higher psychological well-being scores, a higher level of independence scores, and lower viral load more likely to have better immunological stages through the follow-up time.Conclusion: It can be concluded that the multilevel non-proportional-odds method provides a flexible modeling alternative when the proportional-odds assumption of equal effects of the predictor variables at every stage of the response variable is violated. Having higher clinical parameter scores, higher QoL scores, higher educational levels, and stable sexual partners were found to be the significant factors for trends of CD4 count recovery. [ABSTRACT FROM AUTHOR]

Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts< 100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent cryptococcal meningitis related deaths. This strategy may also be considered for those persons with a CD4+ T cell count of < 200 cells/uL according the WHO guidelines. However, there is sparse evidence in the literature supporting CrAg screening and pre-emptive antifungal therapy in those HIV-infected persons with this CD4+ T cell counts< 200 cells/μL.Method: We conducted a meta-analysis using data extracted from randomized controlled studies (RCTs) and cohort studies found in a search of Pubmed, Web of Science, the Cochrane Library and the EMBASE/MEDLINE database.Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4+ T cell counts< 200 cells/μL was 5% (95%CI: 2-7). The incidence of CM in CrAg+ persons was 3% (95%CI: 1-6). Among those CrAg+ persons who did not receive pre-emptive treatment, or those who received placebo, the incidence of CM was 5% (95%CI: 2-9), whereas the incidence of CM among those who received pre-emptive antifungal therapy was 3% (95%CI: 1-6), which is a statistically significant reduction in incidence of 40% (RR: 7.64, 95%CI: 2.96-19.73, p < 0.00001). As for persons with CD4+ T cell counts between 101 ~ 200 cells/μL, the risk ratio for the incidence of CM among those receiving placebo or no intervention was 1.15, compared to those receiving antifungal treatment (95%CI: 0.16-8.13).Conclusions: In our meta-analysis the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4 <  200 cells/μL. However, more specific observational data in persons with CD4+ T cell counts between 101 ~ 200 cells/μL are required in order to emphasize specific benefit of CrAg screening and pre-emptive antifungal treating in CrAg+ persons with CD4+ T cell counts < 200 cells/μL. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. Methods: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L−(effector-memory) and CD45RO−CD62L+ (naïve), using logistic and linear regression models, respectively. Results: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39–48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7–10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: − 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). Conclusions: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH. [ABSTRACT FROM AUTHOR]

Background: Modelling of longitudinal biomarkers and time-to-event data are important to monitor disease progression. However, these two variables are traditionally analyzed separately or time-varying Cox models are used. The former strategy fails to recognize the shared random-effects from the two processes while the latter assumes that longitudinal biomarkers are exogenous covariates, resulting in inefficient or biased estimates for the time-to-event model. Therefore, we used joint modelling for longitudinal and time-to-event data to assess the effect of longitudinal CD4 count on mortality.Methods: We studied 4014 patients from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) who initiated ART between June 2004 and August 2013. We used proportional hazards regression model to assess the effect of baseline characteristics (excluding CD4 count) on mortality, and linear mixed effect models to evaluate the effect of baseline characteristics on the CD4 count evolution over time. Thereafter, the two analytical approaches were amalgamated to form an advanced joint model for studying the effect of longitudinal CD4 count on mortality. To illustrate the virtues of the joint model, the results from the joint model were compared to those from the time-varying Cox model.Results: Using joint modelling, we found that lower CD4 count over time was associated with a 1.3-fold increase in the risk of death, (HR: 1.34, 95% CI: 1.27-1.42). Whereas, results from the time-varying Cox model showed lower CD4 count over time was associated with a 1.2-fold increase in the risk of death, (HR: 1.17, 95% CI: 1.12-1.23).Conclusions: Joint modelling enabled the assessment of the effect of longitudinal CD4 count on mortality while correcting for shared random effects between longitudinal and time-to-event models. In the era of universal test and treat, the evaluation of CD4 count is still crucial for guiding the initiation and discontinuation of opportunistic infections prophylaxis and assessment of late presenting patients. CD4 count can also be used when immunological failure is suspected as we have shown that it is associated with mortality. [ABSTRACT FROM AUTHOR]

Background: Patients infected with HIV may experience a succession of clinical stages before the disease diagnosis and their health status may be followed-up by tracking disease biomarkers. In this study, we present a joint multistate model for predicting the clinical progression of HIV infection which takes into account the viral load and CD4 count biomarkers.Methods: The data is from an ongoing prospective cohort study conducted among antiretroviral treatment (ART) naïve HIV-infected women in the province of KwaZulu-Natal, South Africa. We presented a joint model that consists of two related submodels: a Markov multistate model for CD4 cell count transitions and a linear mixed effect model for longitudinal viral load dynamics.Results: Viral load dynamics significantly affect the transition intensities of HIV/AIDS disease progression. The analysis also showed that patients with relatively high educational levels (β = - 0.004; 95% confidence interval [CI]:-0.207, - 0.064), high RBC indices scores (β = - 0.01; 95%CI:-0.017, - 0.002) and high physical health scores (β = - 0.001; 95%CI:-0.026, - 0.003) were significantly were associated with a lower rate of viral load increase over time. Patients with TB co-infection (β = 0.002; 95%CI:0.001, 0.004), having many sex partners (β = 0.007; 95%CI:0.003, 0.011), being younger age (β = 0.008; 95%CI:0.003, 0.012) and high liver abnormality scores (β = 0.004; 95%CI:0.001, 0.01) were associated with a higher rate of viral load increase over time. Moreover, patients with many sex partners (β = - 0.61; 95%CI:-0.94, - 0.28) and with a high liver abnormality score (β = - 0.17; 95%CI:-0.30, - 0.05) showed significantly reduced intensities of immunological recovery transitions. Furthermore, a high weight, high education levels, high QoL scores, high RBC parameters and being of middle age significantly increased the intensities of immunological recovery transitions.Conclusion: Overall, from a clinical perspective, QoL measurement items, being of a younger age, clinical attributes, marital status, and educational status are associated with the current state of the patient, and are an important contributing factor to extend survival of the patients and guide clinical interventions. From a methodological perspective, it can be concluded that a joint multistate model approach provides wide-ranging information about the progression and assists to provide specific dynamic predictions and increasingly precise knowledge of diseases. [ABSTRACT FROM AUTHOR]

Background: There are few data on the prevalence of acquired drug resistance mutations (ADRs) in Hunan Province, China, that could affect the effectiveness of antiretroviral therapy (ART). Objectives: The main objectives of this study were to determine the prevalence of acquired drug resistance (ADR) the epidemic characteristics of HIV-1-resistant strains among ART-failed HIV patients in Hunan Province, China. Methods: ART-experienced and virus suppression failure subjects in Hunan between 2012 and 2017 were evaluated by genotyping analysis and mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility. Results: The prevalence of HIV-1 ADR were 2.76, 2.30, 2.98, 2.62, 2.23and 2.17%, respectively, from 2012 to 2017. Overall 2295 sequences were completed from 2932 ART-failure patients, and 914 of these sequences were found to have drug resistance mutation. The most common subtype was AE (64.14%), followed by BC (17.91%) and B (11.50%). Among those 914 patients with drug resistance mutations,93.11% had NNRTI-associated drug resistance mutations, 74.40% had NRTI drug resistance mutations (DRMs) and 6.89% had PI DRMs. Dual-class mutations were observed in 591 (64.66%) cases, and triple-class mutations were observed in 43 (4.70%) cases. M184V (62.04%), K103N (41.90%) and I54L (3.83%) were the most common observed mutations, respectively, in NRTI-, NNRTI- and PI-associated drug resistance. 93.76% subjects who had DRMs received the ART first-line regimens. CD4 count, symptoms in the past 3 months, and ART adherence were found to be associated with HIV-1 DR. Conclusions: This study showed that although the prevalence of HIV-acquired resistance in Hunan Province is at a low-level, the long-term and continuous surveillance of HIV ADR in antiretroviral drugs (ARVs) patients is necessary. [ABSTRACT FROM AUTHOR]

Background: Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality.Methods: At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation.Results: We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees.Conclusions: Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed.Trial Registration: Retrospectively registered: ClinicalTrials.gov (NCT02538952). [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: Early presentation for HIV care is vital as an initial tread in the UNAIDS 90-90-90 targets. However, late presentation for HIV care (LP) challenges achieving the targets. This study assessed the prevalence, trends, outcomes and risk factorsfor LP.Methods: A 12 year retrospective cohort study was conducted using electronic medical records extracted from an antiretroviral therapy (ART) clinic at Jimma University Teaching Hospital. LP for children refers to moderate or severe immune-suppression, or WHO clinical stage 3 or 4 at the time of first presentation to the ART clinics. LP for adults refers to CD4 lymphocyte count of < 200 cells/ μl and < 350 cells/μl irrespective of clinical staging, or WHO clinical stage 3 or 4 irrespective of CD4 count at the time of first presentation to the ART clinics. Binary logistic regression was used to identify factors that were associated with LP, and missing data were handled using multiple imputations.Results: Three hundred ninety-nine children and 4900 adults were enrolled in ART care between 2003 and 15. The prevalence of LP was 57% in children and 66.7% in adults with an overall prevalence of 65.5%, and the 10-year analysis of LP showed upward trends. 57% of dead children, 32% of discontinued children, and 97% of children with immunological failure were late presenters for HIV care. Similarly, 65% of dead adults, 65% of discontinued adults, and 79% of adults with immunological failure presented late for the care. Age between 25- < 50 years (AOR = 0.4,95% CI:0.3-0.6) and 50+ years (AOR = 0.4,95% CI:0.2-0.6), being female (AOR = 1.2, 95% CI: 1.03-1.5), having Tb/HIV co-infection (AOR = 1.6, 95% CI: 1.09-2.1), having no previous history of HIV testing (AOR = 1.2, 95% CI: 1.1-1.4), and HIV care enrollment period in 2012 and after (AOR = 0.8, 95% CI: 0.7-0.9) were the factors associated with LP for Adults. For children, none of the factors were associated with LP.Conclusions: The prevalence of LP was high in both adults and children. The majority of both children and adults who presented late for HIV care had died and developed immunological failure. Effective programs should be designed and implemented to tackle the gap in timely HIV care engagement. [ABSTRACT FROM AUTHOR]

Background: The outbreak of the Ebola virus disease (EVD) in 2014 led to massive dropouts in HIV care in Guinea. Meanwhile, Médecins Sans Frontières (MSF) was implementing a six-monthly appointment spacing approach adapted locally as Rendez-vous de Six Mois (R6M) with an objective to improve retention in care. We sought to evaluate this innovative model of ART delivery in circumstances where access to healthcare is restricted.Methods: A retrospective cohort study in 2014 of the outcome of a group of stable patients (viral load ≤1000 copies/μl) enrolled voluntarily in R6M compared with a group of stable patients continuing standard one to three monthly visits in Conakry. Log-rank test and Cox proportional hazards model were used to compare rates of attrition (deaths and defaulters) from care between the two groups. A linear regression analysis was used to describe the trend or pattern in the number of clinical visits over time.Results: Included were 1957 adults of 15 years old and above of whom 1166 (59.6%) were enrolled in the R6M group and 791 (40.4%) in the standard care group. The proportion remaining in care at 18 months and beyond was 90% in the R6M group; significantly higher than the 75% observed in the control group (p < 0.0001). After adjusting for duration on ART and tuberculosis co-infection as covariates, the R6M strategy was associated with a 60% reduction in the rate of attrition from care compared with standard care (adjusted Hazard Ratio = 0.40, 95%CI: 0.27-0.59, p < 0.001). There was a negative secular trend in the number of monthly clinical visits for 24 months as the predicted caseload reduced on average by just below 50 visits per month (β = -48.6, R2 = 0.82, p < 0.0001).Conclusion: R6M was likely to reduce staff workload and to mitigate attrition from ART care for stable patients in Conakry despite restricted access to healthcare caused by the devastating EVD on the health system in Guinea. R6M could be rolled out as the model of care for stable patients where and when feasible as a strategy likely to improve retention in HIV care. [ABSTRACT FROM AUTHOR]

Background: The Marginal Structural Cox Model (Cox-MSM), an alternative approach to handle time-dependent confounder, was introduced for survival analysis and applied to estimate the joint causal effect of two time-dependent nonrandomized treatments on survival among HIV-positive subjects. Nevertheless, Cox-MSM performance in the case of multiple treatments has not been fully explored under different degree of time-dependent confounding for treatments or in case of interaction between treatments. We aimed to evaluate and compare the performance of the marginal structural Cox model (Cox-MSM) to the standard Cox model in estimating the treatment effect in the case of multiple treatments under different scenarios of time-dependent confounding and when an interaction between treatment effects is present.Methods: We specified a Cox-MSM with two treatments including an interaction term for situations where an adverse event might be caused by two treatments taken simultaneously but not by each treatment taken alone. We simulated longitudinal data with two treatments and a time-dependent confounder affected by one or the two treatments. To fit the Cox-MSM, we used the inverse probability weighting method. We illustrated the method to evaluate the specific effect of protease inhibitors combined (or not) to other antiretroviral medications on the anal cancer risk in HIV-infected individuals, with CD4 cell count as time-dependent confounder.Results: Overall, Cox-MSM performed better than the standard Cox model. Furthermore, we showed that estimates were unbiased when an interaction term was included in the model.Conclusion: Cox-MSM may be used for accurately estimating causal individual and joined treatment effects from a combination therapy in presence of time-dependent confounding provided that an interaction term is estimated. [ABSTRACT FROM AUTHOR]

Background: The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment.Methods: Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses.Results: Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24-41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318-535). Pre-treatment spot samples had a higher yield of positive Ziehl-Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan-Meier analyses in either EMS or spot samples.Conclusions: Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples. [ABSTRACT FROM AUTHOR]

Background: Early HIV diagnosis and initiation onto antiretroviral therapy may prevent ongoing spread of HIV. Risk Tracing Snowball Approach (RTSA) has been shown to be effective in detecting new HIV cases in other settings. The main objective of this study is to evaluate the effectiveness of RTSA in increasing the rate of newly identified HIV cases among high-risk populations. Our second objective was to evaluate the effectiveness of RTSA, as compared to the walk-in group, in increasing the number of HIV tests and early case detection.Methods: This study was conducted from April 1 to September 30, 2016 at two NGO clinics in Phnom Penh, Cambodia. Respondent driven sampling method was adapted to develop RTSA to reach high-risk populations, including key populations and the general population who have social connections with key populations. Bivariate and multivariate logistic regression analyses were conducted.Results: During the implementation period, 721 clients walked in for HIV testing (walk-in group), and all were invited to be seeds. Of the invited clients, 36.6% agreed to serve as seeds. Throughout the implementation, 6195 coupons were distributed to seeds or recruiters, and resulted in 1572 clients visiting the two clinics with coupons (RTSA group), for a coupon return rate of 25.3%. The rate of newly identified HIV cases among the RTSA group was significantly lower compared to that in walk-in group. However, the highest number of newly identified HIV cases was found during the implementation period, compared to both pre- and post-implementation period. Although statistically not significant, the mean CD4 count of newly identified HIV cases detected through RTSA was almost 200 cells/mm3 higher than that in the walk-in group.Conclusions: Although the rate of newly identified HIV cases among the RTSA group was lower than that in the walk-in group, the inclusion of RTSA in addition to the traditional walk-in method boosted new HIV case detection in the two participating clinics. A higher mean CD4 count for the RTSA group may reveal that RTSA may be able to detect HIV cases earlier than the traditional walk-in approach. Further research is needed to understand whether RTSA is a cost-effective intervention to prevent ongoing spread of the HIV among high-risk populations in Cambodia. [ABSTRACT FROM AUTHOR]

Background: Mango mistletoes Dendrophthoe pentandra (MMDP) extract has attracted interest due to its pharmacological properties, including gastro protective effects. The aim of this study was to investigate whether MMDP extract could increase Foxp3 regulatory T cells and inhibits development of Th 17 cells. Methods: Colitis was induced in Balb/c mice by rectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice were randomly divided into five groups comprising group1 receiving vehicle (the negative control), group 2-5 receiving TNBS, group 3-5 orally receiving either MMDP extract 150, 300 and 600 mg/kgBW for 7 days after TNBS administration. On day 8 of the experiment, the colon tissues were removed for histological examination, cytokine and myeloperoxidase (MPO) measurement. T-cells sub-population in mesenteric lymph nodes were analyzed by flow cytometer. Results: MMDP extract potently suppressed colon shortening and MPO in mice with TNBS-induced colitis. Administration of the extract significantly decreased the severity of TNBS-induced colitis in a dose-dependent manner. The extract significantly attenuated the loss of body weight (p < 0.05). These effects were associated with a remarkable amelioration of the disruption of the colonic architecture, significant reduction of the colonic MPO (p < 0.05). The extract lowered the levels of Th17-associated cytokines but increased the production of Treg-associated cytokines in mesenteric lymph node cells. Conclusion: Our results suggest that MMDP has the therapeutic potential to ameliorate TNBS-induced colitis symptoms revealed by histological change and inhibit IL-17 production. [ABSTRACT FROM AUTHOR]

Background: Improving child survival for HIV-infected children remains an important health agenda. We present progress regarding care and treatment services to HIV infected children in Tanzania.Methods: The National AIDS Control Programme Care and Treatment (CTC 2) database was used to obtain information of all children aged 0-14yearsenrolled in the HIV Care and Treatment Program between January 2011 and December 2014. We assessed eligibility for ART, time from enrolment to ART initiation, nutritional status, and mortality using Kaplan-Meier methods.Results: A total of 29,531 (14,304 boys and 15,227 girls) ART-naive children aged 0-14 years were enrolled during the period, approximately 6700 to 8000 children per year. The male to female ratio was 48:50. At enrolment 72% were eligible for ART, 2-3% of children were positive for TB, and 2-4% were severely malnourished. Between 2011 and 2014, 2368 (8%) died, 9243 (31%) were Lost to Follow-up and 17,920 (61%) were on care or ART. The probability of death was 31% (95% CI 26-35), 43% (40-47), 52% (49-55) and 61% (58-64) by 1,2, 5 and 10 years of age, respectively. The hazard of death was greatest at very young ages (<2 years old), and decreased sharply by 4 years old. Children who were on ART had around 10-15% higher survival over time.Conclusions: Significant progress has been made regarding provision of paediatric HIV care and treatment in Tanzania. On average 7000 children are enrolled annually, and that approximately two thirds of children diagnosed under the age of 2 years were initiated on ART within a month. Provision of ART as soon as the child is diagnosed is the biggest factor in improving survival. However we noted that i) most children had advanced disease at the time of enrolment ii) approximately two-thirds of children were missing a baseline CD4 measurement and only 35% of children had either a CD4 count or percentage recorded, indicating limited access to CD4 testing services, and iii) 31% were lost to follow-up (LTFU). These challenges need to be addressed to improve early detection, enrolment and retention of HIV-infected children into care and improve documentation of services offered. [ABSTRACT FROM AUTHOR]