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ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts., Methods: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD., Results: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log 10 viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD., Conclusions: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Joint models are a powerful class of statistical models which apply to any data where event times are recorded alongside a longitudinal outcome by connecting longitudinal and time-to-event data within a joint likelihood allowing for quantification of the association between the two outcomes without possible bias. In order to make joint models feasible for regularization and variable selection, a statistical boosting algorithm has been proposed, which fits joint models using component-wise gradient boosting techniques. However, these methods have well-known limitations, i.e., they provide no balanced updating procedure for random effects in longitudinal analysis and tend to return biased effect estimation for time-dependent covariates in survival analysis. In this manuscript, we adapt likelihood-based boosting techniques to the framework of joint models and propose a novel algorithm in order to improve inference where gradient boosting has said limitations. The algorithm represents a novel boosting approach allowing for time-dependent covariates in survival analysis and in addition offers variable selection for joint models, which is evaluated via simulations and real world application modelling CD4 cell counts of patients infected with human immunodeficiency virus (HIV). Overall, the method stands out with respect to variable selection properties and represents an accessible way to boosting for time-dependent covariates in survival analysis, which lays a foundation for all kinds of possible extensions., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Colin Griesbach et al.)

Abstract: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To analyze the modifications of CD4 T cell, CD4/CD8 ratio, and serum levels of soluble CD14 (sCD14) in HIV/HCV-coinfected patients after treatment with direct anti-HCV antiviral agents. Consecutive cases of HIV/HCV-coinfected patients, attended at the University Hospital, who achieved sustained virological responses with interferon-free hepatitis C antiviral drugs, were analyzed. Thirty-five percent of patients (n = 39) had been diagnosed with liver cirrhosis. The evaluation criteria were changes in CD4 T-cell counts and percentages and inflammation (measured by serum sCD14 levels) or immune activation indexes (determined by CD4/CD8 ratio) from beginning anti-HCV therapy to 12 months later. One hundred twelve patients were included (87% male; median age, 54 years; median time from the infection diagnosis, 22 years; previous drug users, 87%). Significant increases in CD4 T cell count and percentage were detected only in individuals without liver cirrhosis. No significant differences in CD4/CD8 ratios or sCD14 levels were observed in patients with or without cirrhosis. The proportion of patients with less than 500 CD4 T cell/mm 3 before therapy who achieved more than 500 CD4 T cell/mm 3 after it increased only in the group without liver cirrhosis. The finding that CD4 T cell count and percentage were improved only in patients without liver cirrhosis supports the idea that treatment against HCV in HIV/HCV-coinfected patients is needed in the early phases of liver disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult., Objective: Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium)., Methods: Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020., Results: Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4 + T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia., Conclusions: Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum.

Background: Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa's national HIV program using routine laboratory data., Methods and Findings: Data were extracted from South Africa's National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study's limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape., Conclusions: We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease., Competing Interests: The authors have declared that no competing interests exist.

Information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in HIV-infected individuals is scarce. In this prospective study, we included HIV (human immunodefeciency virus)-infected individuals (people living with HIV [PLWHIV]) with confirmed SARS-CoV-2 infection and compared them with PLWHIV negative for SARS-CoV-2. We compared 55 cases of SARS-CoV-2 infection with 69 asymptomatic PLWHIV negative for SARS-CoV-2 reverse transcription-polymerase chain reaction and/or serology. There was no significant difference between SARS-CoV-2 positive or negative patients for age distribution, gender, time with HIV infection, nadir CD4-cell counts, type and number of co-morbidities, current CD4 and CD8 counts and type of anti-HIV therapy. Positive patients presented with a median of three symptoms (interquartile range, 1-3). Most common symptoms were fever (76%), dyspnea (35%), anosmia (29%) non-productive cough (27%), fatigue 22%), and ageusia (20%). Ten patients (18%) were completely asymptomatic. Four (7.2%) subjects died of coronavirus disease 2019. Factors significantly (P < .05) associated with death included age and number of co-morbidities, while time from HIV infection and lower current CD4 counts were significant only in univariate analysis. HIV-infected individuals are not protected from SARS-CoV-2 infection or have a lower risk of severe disease. Indeed, those with low CD4 cell counts might have worse outcomes. Infection is asymptomatic in a large proportion of subjects and this is relevant for epidemiological studies., (© 2020 Wiley Periodicals LLC.)

Objectives: National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART., Methods: CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count < 200 cells/µL) at initial CD4 assessment, (2) the proportion with an initial CD4 count ≥ 200 cells/µL experiencing a subsequent decline in CD4 count to < 200 cells/µL, and (3) the proportion of these immunologically failing individuals who had virological failure. Logistic regression modelling examined factors associated with advanced HIV disease. CD4 count trajectories were assessed using locally weighted scatterplot smoothing (LOWESS) regression., Results: Twenty-five per cent (3571/14 423) of individuals with an initial CD4 assessment during the study period had advanced HIV disease at baseline. Older age [≥ 35 years; adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.8-2.1] and male sex were associated with advanced HIV disease. Fifty per cent (7163/14 423) of individuals had at least two CD4 counts during the study period. Of those with an initial CD4 count ≥ 200 cells/µL, 4% (180/5061) experienced a decline in CD4 count to < 200 cells/µL; the majority of CD4 count declines were in virologically suppressed individuals and transient., Conclusions: One-quarter of HIV-positive individuals in Botswana still present with advanced HIV disease, highlighting the importance of baseline CD4 count measurement to identify this at-risk population. Few with a baseline CD4 count ≥ 200 cells/µL experienced a drop below 200 cells/µL, suggesting limited utility for ongoing CD4 monitoring., (© 2020 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: To analyze influencing factors of instant antiretroviral therapy (ART) and explore associution between strategies of ART and immunological effects among HIV/AIDS patients in Taizhou city during 2006-2019. Methods: A retrospective cohort study was conducted on HIV/AIDS patients under ART, and a logistic regression model was used to analyze factors of instant ART. The student t -test and chi-square test were used to compare immunological effect of different ART strategies while the Kaplan-Meier method was used to generate a survival curve. Results: A total of 2 971 HIV/AIDS patients were enrolled with 1 786 cases (60.1%) having instant ART strategy. The proportion of instant ART were 77.8% (1 170/1 504) during 2016 to 2019. The treatment success rate of the instant ART group (87.4%, 1 561/1 786) were higher than the delayed ART group (84.4%, 1 000/1 185). The results of multivariate logistic regression model indicated that male (a OR =1.28, 95 %CI : 1.03-1.59), married (a OR =1.71, 95 %CI : 1.33-2.19) and baseline CD(4)(+)T lymphocyte cells (CD(4)) counts ≤200 cells/μl (a OR =1.60, 95 %CI : 1.27-2.02) were factors positively related to instant ART while 31-40 years old (a OR =0.63, 95 %CI : 0.48-0.84), infected through heterosexual transmission(a OR =0.60, 95 %CI : 0.49-0.74) and diagnosed before 2015 (a OR =0.20, 95 %CI : 0.17-0.23) were inversely related to instant ART. The increase of the CD(4)/CD(8) ratio was greater, and the cumulative ART success rate was higher each year in the instant ART group than in the delayed ART group ( P <0.05). Conclusions: The instant ART strategy has been well implemented in Taizhou city during 2006-2019, and the immunological effect was better in instant ART group. The proportion of instant ART were more than 60.0% among HIV/AIDS patients. Instant ART strategy needs to be strengthened for those who are 31-40 years old, women, unmarried, and infected through heterosexual transmission in an attempt to further increase treatment level and improve treatment effect.

Purpose: To estimate time from seroconversion to diagnosis, researchers have modeled time based on CD4 decline, assuming the square root of the CD4 count decreases linearly over time before antiretroviral treatment (ART) initiation. If true, utilizing CD4 counts reported anytime in the pre-ART period would result in estimates of diagnosis delay that are not appreciably different., Methods: We applied CD4 depletion model parameters from seroconverter cohorts to New York City residents diagnosed from 2006 to 2015, having two or more pre-ART CD4 counts., Results: Median diagnosis delays based on first or second pre-ART CD4 counts were similar (n = 12,849; 2.8 years, interquartile range [IQR]: 0-7.7, and 2.8 years, IQR: 0-7.6, respectively; P = .09, Wilcoxon signed-rank test). Among people whose second pre-ART CD4 count was measured more than 6 months after diagnosis (n = 2761), the average diagnosis delay based on first pre-ART CD4 count was shorter (1.5 years, IQR: 0-5.4) than the second pre-ART CD4 count (1.7 years, IQR: 0-6.0) but not significantly (P = .12)., Conclusions: Results are consistent with the linearity assumption of the CD4 depletion model. To estimate population-level diagnosis delay, researchers may use pre-ART CD4 counts reported more than 6 months post-diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

Human immunodeficiency virus (HIV) supresses immune system, primarily cell-mediated immunity. Cluster of differentiation 4 (CD4) cell count, viral load, and oral lesions are the most important laboratory parameters to evaluate the evolution of acquired immunodeficiency syndrome. The present study aims to determine the incidence of HIV-related oral lesions with CD4 cell count and viral load in Yunnan, China.A cross-sectional study was conducted from December 2007 to December 2009, in 1812 HIV positive patients from Department of Infectious Diseases in Kunming Third People's Hospital. CD4, CD8, and viral load data were collected and analyzed statistically using SPSS 11.3.Out of 1812 HIV positive patients, 929 (51.27%) were associated with 1 or more oral lesions. The most common oral lesions observed were Candida Pseudomembranous (13.75%), Candida erythematous (10.93%), Oral hairy leukoplakia (7.95%), Aphthous ulcer (6.18%), Herpes simplex infection (5.58%). In most patients with oral lesions, the CD4 cell count was < 200/μL. The incidence of oral lesions was lower when CD4 count was > 200/μL and with undetectable (P < .01) HIV viral load. Almost no oral lesions was observed when CD4 count > 500/μL (P < .01). With highly active antiretroviral therapy, reduction in HIV-related oral lesions was observed especially in Candida erythematous, Candida Pseudomembranous, Oral hairy leukoplakia, and Aphthous ulcer.The higher incidence of oral lesions with lower CD4 count (<200/μL) in HIV-infected patients indicated importance of CD4 cell count in identifying disease progression.

Introduction: End-stage renal disease (ESRD) related to HIV is becoming a leading cause of renal replacement therapy requirement is some areas of the world. Our study aims to describe the incidence and renal outcomes of HIV-associated nephropathy (HIVAN), and immune-mediated kidney disease related to HIV (HIVICK) in Colombia., Methodology: A retrospective cohort study was performed, including all HIVAN or HIVICK incident cases assessed by the infectious diseases division in a high complexity institution in Colombia, between 2004 and 2018. A longitudinal data model under the Generalized Estimating Equations (GEE) method was used to determine changes on the glomerular filtration rate (GFR) over time., Results: Within a cohort composed by 1509 HIV-infected patients, we identified 22 with HIV-associated glomerular disease. Cumulative incidence was 1.45%. At diagnosis, GFR was above 30 mL/min in 90.8% of patients, and 77.2% displayed sub-nephrotic proteinuria. Factors associated with GFR at diagnosis were: level of CD4 (Coefficient 0.113, CI 95 %: 0.046, 0.179, p < 0.01), and the inverse of the CD4/CD8 ratio. The GEE model did not demonstrate significant changes in the GFR over a 3-year period. Findings were similar when comparing GFR at diagnosis with GFR at 12 (-3.9 mL/min/1.73m2, CI 95% -7.3, 0.4, p = 0.98), 24 (-2.47 mL/min/1.73m2, CI 95% -7.0, 2.1, p=0.85), and 36 months (0.39 mL/min/1.73m2, CI 95% -4.4, 5.2, p = 0.43) of follow-up., Conclusions: Patients with glomerular disease associated with HIV have stable GFR over a 3-year period, and low rates of progression towards dialysis requirement. Differences with previous reports could be related with early diagnosis and treatment with highly active antiretroviral therapy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Oscar Munoz-Velandia, Angel Garcia-Pena, Javier Garzon-Herazo, Kateir Contreras-Villamizar, Martha Rodriguez-Sanchez, Elias Garcia-Consuegra, Esteban Toro-Trujillo.)

The impact of sociodemographic and clinical factors on immune recovery and viral load suppression among HIV-1 positive patients treated with HAART particularly in Malaysia is largely unknown. This cross-sectional study enrolled 170 HIV-1-infected individuals of three major ethnicities who attended three HIV outpatient clinics in Malaysia. Questionnaire was used to obtain sociodemographic data while CD4 count and viral load data were gathered from hospital's record. Multiple factors were assessed for their predictive effects on CD4 count recovery (≥500 cells/mm 3 ) and viral load suppression (≤50 copies/mL) using binary logistic regression. Most of the subjects were male (149/87.6%), in the age group 30 to 39 years old (78/45.9%) and got infected via homosexual contact (82/48.2%). Indians were associated with 11 times higher chance for CD4 recovery as compared to Malays at 8 to 12 months of HAART (adjusted OR: 10.948, 95% CI: 1.873, 64.001, P = .008). Viral load suppression was positively influenced by intravenous drug use (IVDU) status (adjusted OR: 35.224, 95% CI: 1.234, 1000.489, P = .037) at 4 to 6 months of HAART. Higher pretreatment CD4 count was a positive predictor for both initial immunological and virological responses while higher pretreatment viral load was a negative predictor for virological suppression only. In conclusion, ethnicity plays a significant role in determining early immune reconstitution in Malaysia, besides pretreatment CD4 count. Further studies are needed to identify possible biological factors underlying this association., (© 2020 Wiley Periodicals, Inc.)

Background & Aims: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic., Methods: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators., Results: An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/μl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence., Conclusions: This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden., Lay Summary: Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint., Competing Interests: Conflicts of interest The authors do not have potential conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. All rights reserved.)

Objectives. To evaluate the impact of duration and service category on HIV health outcomes among low-income adults living with HIV and enrolled in a housing program in 2014 to 2017. Methods. We estimated relative risk of engagement in care, viral suppression, and CD4 improvement for 561 consumers at first and second year after enrollment to matched controls through the New York City HIV surveillance registry, by enrollment length (enrolled for more than 1 year or not) and service category (housing placement assistance [HPA], supportive permanent housing [SPH], and rental assistance [REN]). Results. The SPH and REN consumers were enrolled longer and received more services, compared with HPA consumers. Long-term SPH and REN consumers had better engagement in care, viral suppression, and CD4 count than controls at both first and second year after enrollment, but the effect did not grow bigger from year 1 to 2. HPA consumers did not have better outcomes than controls regardless of enrollment length. Conclusions. Longer enrollment with timely housing placement and a higher number and more types of services are associated with better HIV health outcomes for low-income persons living with HIV with unmet housing needs.

Mediator models have been developed primarily under the assumption of no-unmeasured-confounding. In many situations, this assumption is violated and may lead to the identification of mediator variables that actually are statistical artifacts. The rank preserving model (RPM) is an alternative approach to estimate controlled direct and mediator effects. It is based on the structural mean models framework and a no-effect-modifier assumption. The RPM assumes that unobserved confounders do not interact with treatment or mediators. This assumption is often more plausible to hold than the no-unmeasured-confounder assumption. So far, models using the no-effect-modifier assumption have been rarely used, which might be due to its low power and inefficiency in many scenarios. Here, a semi-parametric nonlinear extension, the nRPM, is proposed that overcomes this inefficiency using thin plate regression splines that both increase the predictive power of the model and decrease the misspecification present in many situations. In a simulation study, it is shown that the nRPM provides estimates that are robust against the violation of the no-effect-modifier assumption and that are substantively more efficient than those of the RPM. The model is illustrated using a data set on CD4 cell counts in a context of the human immunodeficiency virus (HIV).

Objective: To understand the progression of CD(4)(+) T cells (CD(4)) declining rate in different age groups among MSM and to further explore the pathogenesis of HIV infection. Methods: Data regarding MSM who were diagnosed as HIV positive, aged ≥15 years, with homosexual route of transmission and with more than two records of CD(4) count retained before antiretroviral therapy (ART), were collected from the National AIDS Comprehensive Prevention Information System until May 31, 2019. Linear mixed effect model was used to fit the linear elimination relationship between the square root of CD(4) cell count and infection time before taking up the ART. To get the intercept estimation, we used the results from CD(4) count which containing the dates of last negativity and first positivity on HIV antibody testing. Both t test and Z test were used to test the model parameters. Median intervals from HIV seroconversion to CD(4)<500, <350, <200 cells/μl were estimated. Results: A total of 26 754 individuals were included in the study including 146 of them having records on the last date of being test negative. Their median age was 27 years old ( M =27, P ( 25 )- P ( 75 ):23-35). The intercept of the liner mixed models among 15-, 25- and ≥35 year olds were 24.84 (95 %CI : 23.76-25.92), 23.94 (95 %CI : 22.86-25.02), 23.44 (95 %CI : 21.91-24.96) and the slope of the liner mixed models among the 15-24, 25-34, 35-44 and ≥45 year olds were -1.31 (95 %CI : -1.33--1.25), -1.37(95 %CI : -1.40--1.33), -1.53 (95 %CI : -1.58--1.47) and -1.59 (95 %CI :-1.68--1.51), respectively. Estimation on the median intervals from HIV seroconversion to CD(4) <500, <350, <200 cells/μl counts were 1.29 (95 %CI : 0.79-1.81), 3.92 (95 %CI : 3.36-4.48) and 7.21 (95 %CI : 6.58-7.81), respectively. The median time of 15-24 age group from HIV seroconversion to reach the three CD(4) thresholds appeared the longest, as 1.89 (95 %CI : 1.05-2.85), 4.68(95 %CI : 3.80-5.77) and 8.17 (95 %CI : 7.23-9.42) years, respectively, the median time of ≥45 age group from HIV seroconversion to reach the three CD(4) thresholds appeared the shortest, as 0.68 (95 %CI : 0.00-1.72)、2.98 (95 %CI : 1.91-4.14)、5.85 (95 %CI : 4.62-7.16) years, respectively. Conclusions: Our findings suggested that the CD(4) declining rate had been accelerated along with ageing. Progression time from HIV seroconversion to different CD(4) thresholds appeared different, which was shorter in the older age group. Again, these findings showed the great impact of HIV infection among older age groups in the MSM population. Early diagnosis and treatment were bound to delay the progression of the disease.

Background: Quality of human immunodeficiency virus (HIV) care in nursing homes (NHs) has never been measured., Design: A cross-sectional study., Setting: NHs., Participants: A total of 203 NHs and 1375 persons living with HIV., Measurements: Medicare claims from 2011 to 2013 were linked to assessments of resident health, prescription dispensing data, and national reports of NH characteristics. Five nationally validated HIV care quality measures (prescription of antiretroviral therapy; CD4/viral load monitoring; frequency of medical visits; gaps in medical visits; and Pneumocystis pneumonia prophylaxis) were adapted and applied to NHs. Logistic regression predicted compliance by organizational factors. Random intercept logistic regression predicted if persons living with HIV received care by person and organizational factors., Results: Compliance ranged from 43.3% (SD = 31.1%) for CD4/viral load monitoring to 92.4% (SD = 13.6%) for gaps in medical visits. More substantiated complaints against an NH decreased the likelihood of high compliance with CD4/viral load monitoring (odds ratio [OR] = 0.846; 95% confidence interval [CI] = 0.726-0.986), while NH-reported incidents increased the likelihood of high compliance with pneumocystis pneumonia prophylaxis (OR = 1.173; 95% CI = 1.044-1.317). Differences between NHs explained 21.2% or less of variability in receipt of care., Conclusions: Since 2013, the population with HIV and NH HIV care quality has inevitably evolved; however, this study provides previously unknown baseline metrics on NH HIV care quality and highlights significant challenges when measuring HIV care in NHs. J Am Geriatr Soc 68:1226-1234, 2020., (© 2020 The American Geriatrics Society.)

Background: Mobile HIV testing services (HTS) are effective at reaching undiagnosed people living with HIV. However, linkage to HIV care from mobile HTS is often poor, ranging from 10 to 60%. Point-of-care (POC) CD4 testing has shown to increase retention in health facilities, but little evidence exists about their use in mobile HTS. This study assessed the feasibility of POC CD4 test implementation and investigated linkage to HIV care among clients accepting a POC test at community-based mobile HTS., Methods: This retrospective study used routinely collected data from clients who utilized community-based mobile HTS in the City of Cape Town Metropolitan district, South Africa between December 2014 and September 2016. A POC CD4 test was offered to all clients with an HIV positive diagnosis during this period, and a CD4 cell count was provided to clients accepting a POC CD4 test. Random effects logistic regression was used to assess factors associated with POC CD4 test uptake and self-reported linkage to care among clients accepting a POC test. Models were adjusted for sex, age, previous HIV test done, tuberculosis status and year of HIV diagnosis., Results: One thousand three hundred twenty-five of Thirty-nine thousand seven hundred ninety clients utilizing mobile HTS tested HIV positive (3%). 51% (679/1325) accepted a POC test. The age group with the highest proportion accepting a POC test was 50+ years (60%). Females were less likely to accept a POC test than males (odds ratio = 0.7, 95%CI = 0.6-0.8). Median CD4 count was 429 cells/μl (interquartile range = 290-584). Among 679 clients who accepted a POC CD4 test, 491 (72%) linked to HIV care. CD4 cell count was not associated with linkage to care., Conclusion: Our findings suggest that mobile HTS can identify early HIV infection, and show that a high proportion of clients with a POC test result linked to care. Future research should assess factors associated with POC test acceptance and assess the impact of POC CD4 testing in comparison to alternative strategies to engage HIV positive people in care.

In longitudinal studies, it is of interest to investigate how repeatedly measured markers are associated with time to an event. Joint models have received increasing attention on analyzing such complex longitudinal-survival data with multiple data features, but most of them are mean regression-based models. This paper formulates a quantile regression (QR) based joint models in general forms that consider left-censoring due to the limit of detection, covariates with measurement errors and skewness. The joint models consist of three components: (i) QR-based nonlinear mixed-effects Tobit model using asymmetric Laplace distribution for response dynamic process; (ii) nonparametric linear mixed-effects model with skew-normal distribution for mismeasured covariate; and (iii) Cox proportional hazard model for event time. For the purpose of simultaneously estimating model parameters, we propose a Bayesian method to jointly model the three components which are linked through the random effects. We apply the proposed modeling procedure to analyze the Multicenter AIDS Cohort Study data, and assess the performance of the proposed models and method through simulation studies. The findings suggest that our QR-based joint models may provide comprehensive understanding of heterogeneous outcome trajectories at different quantiles, and more reliable and robust results if the data exhibits these features.

Background: CD4 cell and viral load count are highly correlated surrogate markers of human immunodeficiency virus (HIV) disease progression. In modelling the progression of HIV, previous studies mostly dealt with either CD4 cell counts or viral load alone. In this work, both biomarkers are in included one model, in order to study possible factors that affect the intensities of immune deterioration, immune recovery and state-specific duration of HIV-infected women., 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. Participants were enrolled in the acute HIV infection phase, then followed-up during chronic infection up to ART initiation. Full-parametric and semi-parametric Markov models were applied. Furthermore, the effect of the inclusion and exclusion viral load in the model was assessed., Results: Inclusion of a viral load component improves the efficiency of the model. The analysis results showed that patients who reported a stable sexual partner, having a higher educational level, higher physical health score and having a high mononuclear component score are more likely to spend more time in a good HIV state (particularly normal disease state). Patients with TB co-infection, with anemia, having a high liver abnormality score and patients who reported many sexual partners, had a significant increase in the intensities of immunological deterioration transitions. On the other hand, having high weight, higher education level, higher quality of life score, having high RBC parameters, high granulocyte component scores and high mononuclear component scores, significantly increased the intensities of immunological recovery transitions., Conclusion: Inclusion of both CD4 cell count based disease progression states and viral load, in the time-homogeneous Markov model, assisted in modeling the complete disease progression of HIV/AIDS. Higher quality of life (QoL) domain scores, good clinical characteristics, stable sexual partner and higher educational level were found to be predictive factors for transition and length of stay in sequential adversity of HIV/AIDS.

Objective: Sudden cardiac death (SCD) plays an important part in all-cause mortality in patients infected with human immunodeficiency virus (HIV). The T-peak to T-end (Tp-e) interval, corrected Tp-e (Tp-ec) interval, and Tp-e/QT ratio on the ECG are parameters used to stratify risk for SCD. The objective of this study was to investigate the differences between HIV-infected patients and healthy individuals in terms of Tp-e interval, Tp-ec interval, and Tp-e/QT ratio, as well as other influencing factors., Methods: Ninety-eight HIV-infected patients and 62 healthy controls were included in this prospective case-control study. Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were measured in all participants. Echocardiographic examination and routine laboratory analysis were performed. In addition, CD4 T-cell count and HIV RNA levels were assessed in HIV-infected patients., Results: All baseline characteristics were comparable in both groups. The median survival of those living with HIV was 20.63 months; 53% of them had controlled viral load, and 74% were receiving antiretroviral therapy. Mean baseline CD4 T-cell count was 409. In HIV-infected patients, the Tp-e interval and Tp-ec interval were prolonged, and the Tp-e/QT ratio was higher (p<0.001, p<0.001 and p=0.021, respectively). In bivariate and partial correlation analyses, there was a negative correlation between CD4 T-cell level and Tp-e interval, Tp-ec interval, and Tp-e/QT ratio., Conclusion: Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were greater in HIV-infected patients compared with healthy individuals. HIV-infected patients, particularly those with low baseline CD4 T-cell counts, should be closely monitored due to risk of SCD., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Early antiretroviral therapy (ART) is recommended as an intervention for HIV by the World Health Organization. However, the association between the CD4 count at ART initiation and the risk of adverse drug reactions (ADRs) remains unclear., Purpose: This study aimed to describe the trends related to symptom number and intensity among patients newly diagnosed with HIV in three different CD4-count-based groups and then to investigate the ADR trends for these three groups at different points in time., Methods: This multi-center cohort study recruited newly diagnosed HIV/AIDS patients who had not previously used ART from AIDS-designated hospitals in Taiwan from March 2015 to December 2016. Study measures were assessed at the time of case enrollment (T0) and during the 1st month (T1), 4-6th month (T2), and 7-9th month (T3) of ART treatment. Patients were stratified into three groups according to initial CD4 count: ≤ 350 cells/mm 3 , >350-500 cells/mm 3 and >500 cells/mm 3 . Repeated measures ANOVA and generalized estimating equations were used to estimate the relationships between the level of initial CD4 count and ADRs., Results: A total of 207 patients completed the study. Mean symptom numbers and symptom intensities decreased significantly over time in all three groups (p < .01). The largest mean reduction in both symptom number and intensity was achieved by the CD4 count >500 cells/mm 3 group. Overall, at least one ADR was reported by 85.7% of the participants at the first month of ART use, and the incidence of ADR had decreased by an average of 22% at the 7-9th month assessment (p < .001). ARDs decreased significantly over time in the CD4 count > 500 cells/mm 3 group, with the degrees of ADRs in systematic side effect most significantly decreased in this group (p = .03)., Conclusions / Implications for Practice: Number and intensity of symptoms significantly improved over time in all three CD4 count groups. The percentage of systematic side effects was most reduced in the CD4 count > 500 cells/mm 3 group. The results of this study may be referenced by HIV care providers when discussing with patients the initiation of ART and the potential risks of experiencing ADRs.

Background. Heterogeneity in HIV microepidemics across US cities necessitates locally oriented, combination implementation strategies to prioritize resources. We calibrated and validated a dynamic, compartmental HIV transmission model to establish a status quo treatment scenario, holding constant current levels of care for 6 US cities. Methods. Built off a comprehensive evidence synthesis, we adapted and extended a previously published model to replicate the transmission, progression, and clinical care for each microepidemic. We identified a common set of 17 calibration targets between 2012 and 2015 and used the Morris method to select the most influential parameters for calibration. We then applied the Nelder-Mead algorithm to iteratively calibrate the model to generate 2000 best-fitting parameter sets. Finally, model projections were internally validated with a series of robustness checks and externally validated against published estimates of HIV incidence, while the face validity of 25-year projections was assessed by a Scientific Advisory Committee (SAC). Results. We documented our process for model development, calibration, and validation to maximize its transparency and reproducibility. The projected outcomes demonstrated a good fit to calibration targets, with a mean goodness-of-fit ranging from 0.0174 (New York City [NYC]) to 0.0861 (Atlanta). Most of the incidence predictions were within the uncertainty range for 5 of the 6 cities (ranging from 21% [Miami] to 100% [NYC]), demonstrating good external validity. The face validity of the long-term projections was confirmed by our SAC, showing that the incidence would decrease or remain stable in Atlanta, Los Angeles, NYC, and Seattle while increasing in Baltimore and Miami. Discussion. This exercise provides a basis for assessing the incremental value of further investments in HIV combination implementation strategies tailored to urban HIV microepidemics.

Purpose: Healthcare spending as a percentage of Gross domestic product (GDP) is at all-time high and continues to rise in the United States. The Centers for Medicare and Medicaid Services estimate that 33% of resources spent on healthcare goes to waste. As part of a 'high value care' exercise, we studied if estimating CD4 cell counts and HIV viral load in hospitalized patients with a known diagnosis of HIV led to any meaningful change in HAART regimen and discharge diagnosis., Methods: Retrospective chart review for all patients admitted with a known diagnosis of HIV from January 1, through December 31, 2017., Results: A total of 83 patient encounters were reviewed during the period. The mean age was 54.1 ± 16.4 years, 64.1 % of patients were males. 75 patients (90.3%) were already on highly active antiretroviral therapy (HAART). The median hospital length of stay (LOS) was 3 days (IQR 2.0 - 5.0). The mean turnaround time for CD4 counts and HIV viral load assay was 2.9 days (95% CI 2.1 - 3.7) and 3.9 days (95% CI, 3.2 - 4.6), respectively. A CD4 count estimation led to no change in HAART regimen. HIV viral load assay testing had no impact on a change in treatment or a change in diagnosis., Conclusions: In our study, testing CD4 counts and HIV viral load for inpatients did not confer any benefit in altering the diagnosis or HAART regimen. We believe that our study identifies a systems level opportunity to add to the concept of 'Choosing Wisely.', (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background The profile of patients with HIV/AIDS is required to develop appropriate HIV/AIDS prevention and treatment programs in Indonesia. Turen is one of the four sub-districts with the highest number of patients with HIV/AIDS in Malang District, Indonesia. The purpose of this study is to determine the sociodemographic profile, sources of infection, use of antiretrovirals and CD4 counts on HIV/AIDS outpatients in Turen Primary Health Centre (PHC). Methods The sociodemographic data, antiretroviral use, and CD4 counts were obtained from medical records on HIV/AIDS outpatients in Turen PHC. A qualitative approach using in-depth interviews was used to explore the source of infection. Descriptive analysis was used to summarise the quantitative data, while thematic analysis was used to analyse the qualitative data derived from interviews. Results A total of 45 HIV/AIDS outpatient medical records were reviewed. Of those, the majority were females (57.8%), ages 26-35 years (51.1%), married (55.6%) and having income less than 2 million rupiah (73.3%). All of them used a combination of antiretroviral therapy from two classes of antiretrovirals, i.e. nucleotide analog reverse transcriptase inhibitor and non-nucleotide analog reverse transcriptase inhibitor; the majority were treated with fixed-dose combination of tenofovir-lamifudin-efavirenz. The CD4 counts data were obtained from 31 patients with an average number of 282 cells/mm3. The qualitative data from interviews with 15 patients revealed that the source of infection was from husband, unsafe/unprotected sex and blood donor. Conclusions The high prevalence of HIV/AIDS among young married women and poor control of the disease in Indonesia warrants further considerations. The government should work together with all related stakeholders in raising awareness of HIV/AIDS, particularly among women, as well as improving treatment and support for people living with HIV/AIDS.

Background: During recent years, Quality of Life (QoL) is a significant assessment factor in clinical trials and epidemiological researches due to the advent of Antiretroviral Therapy (ART), Human Immunodeficiency Virus (HIV) has become a manageable,chronic disease. With regards, more attention must be paid to the QoL of infected patients. Limited evidence exists on the impact of ART on QoL among HIV infected patients. Due to lacking of a systematic approach to summarizing the available evidence on the clinical determinants of People Who Live with HIV/AIDS (PWLHs') QoL, this study aimed to analyze the impact of clinical determinants (ART experience, CD4 count < 200, co-morbidities, time diagnosis and accessibility to cares) on QoL among PWLHs'., Methods: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Science Direct, Web of Science, and Cochrane electronic databases were searched in February 2017 to identify all past studies that discussed social and behavioral characteristics of QoL in PLWHA. To recognize effective factors on social and behavioral QoL, a meta-analysis was conducted. Polled Odds Ratios (ORs) were utilized at a 95% confidence level. Since sampling methods differed between articles in the systematic review, we evaluated pooled estimates using a random effect model. Metan, metareg, metacum, and metabias commands in STATA version 13.0 were applied to analyze the data., Results: Our findings indicated that ART has a positive impact on QoL, with a pooled effect size at approximately 1.04 with a confidence interval between 0.42 to 1.66 which indicates this impact is not very considerable and may be relatively neutral. The pooled effect size for CD4 count on QoL was .29 (95%CI = .22-.35), indicating that there is a negative associate between CD4 count and QoL. The co-morbidity as a negative determinant for QoL among HIV/AIDS infected people. The pooled effect size implies on a relative neutral association, although the confidence interval is wide and ranges between 0.32 to 1.58. The pooled effect size is about 1.82 with confidence interval 1.27 to 2.37 which indicates a considerable positive association with lowest level of heterogeneity., Conclusions: The results illustrated that time diagnosing and availability to hospital services had significant relationship with a higher QoL and CD4 < 200 was associated with a lower QoL. In conclusion, policy makers should set an agenda setting to provide a suitable diagnostic and therapeutic facilities to early detecting and continues monitoring the health status of People Who Live with HIV/AIDS (PWLHs').

HIV infection is associated with increased risk and progression of cardiovascular disease (CVD), yet little is known about the prevalence of CVD risk factors among long-term AIDS survivors in resource-limited settings. Using routinely collected data, we conducted a retrospective study to describe the prevalence of CVD risk factors among a cohort of HIV-infected patients followed for over 10 years in Port-au Prince, Haiti. This cohort includes 910 adults who initiated antiretroviral therapy (ART) between 2003 and 2004 and remained in care between 2014 and 2016 when routine screening for CVD risk factors was implemented at a large clinic in Haiti. A total of 397 remained in care ≥10 years and received screening. At ART initiation, 59% were female, median age was 38 years (IQR 33-44), and median CD4 count was 117 cells/mm 3 (IQR 34-201). Median follow-up time from ART initiation was 12.1 years (IQR 11.7-12.7). At screening, median CD4 count was 574 cells/mm 3 (IQR 378-771), and 84% (282 of 336 screened) had HIV-1 RNA < 1000 copies/mL. Seventy-four percent of patients had at least 1 risk factor including 58% (224/385) with hypertension, 8% (24/297) diabetes, 43% (119/275) hypercholesterolemia, 8% (20/248) active smoking, and 10% (25/245) obesity. Factors associated with hypertension were age (adjusted OR 1.06, P < .001) and weight at screening (adjusted OR 1.02, P = .019). Long-term AIDS survivors have a high prevalence of CVD risk factors, primarily hypertension. Integration of cardiovascular screening and management into routine HIV care is needed to maximize health outcomes among aging HIV patients in resource-limited settings., (©2019 Wiley Periodicals, Inc.)

Background: Alcohol consumption is associated with poor health outcomes in women living with HIV (WLWH), but whether medication can help to reduce drinking in non-treatment-seeking women or whether reduction in drinking improves HIV outcomes is unclear. We conducted a randomized clinical trial (RCT) of daily oral naltrexone (50 mg) versus placebo in WLWH who met criteria for current unhealthy alcohol use., Methods: WLWH with current unhealthy alcohol use (>7 drinks/wk or >3 drinks/occasion) were randomly assigned to daily oral naltrexone 50 mg (n = 96) or placebo (n = 98) for 4 months. Drinking outcomes, including the proportion of women who reduced (

We examined correlates of late and delayed initiation of antiretroviral therapy (ART) in British Columbia, Canada. From December 2013 to December 2015 we recruited treatment-naïve people living with HIV who initiated ART within the previous year. 'Late initiation' was defined as CD4 cell count ≤500 cells/µL at ART initiation and 'delayed initiation' as ≥1 year between HIV diagnosis and initiation. Multivariable logistic regression assessed independent correlates of late and delayed initiation. Of 87 participants, 44 (51%) initiated late and 22 (26%) delayed initiation. Delayed initiation was positively associated with older age (adjusted odds ratio [AOR]: 1.06 per year, 95% confidence interval [95% CI]: 1.01-1.12) and inversely associated with wanting to start ART at diagnosis (AOR: 0.06, 95% CI: 0.02-0.21). Variables associated with late initiation were older age (AOR: 1.09 per year, 95% CI: 1.03-1.15) and medical reason(s) for initiation (AOR: 5.00, 95% CI: 1.41-17.86). Late initiation was less likely among those with greater perceived ART efficacy (AOR 0.94, 95% CI: 0.90-0.98) and history of incarceration (AOR: 0.12, 95% CI: 0.03-0.56). Disparities in timing of initiation were observed for age, perceived ART efficacy, and history of incarceration. Enhanced health services that address these factors may facilitate earlier treatment initiation.

Background: CD4+ T-cell count External Quality Assessment program is important for the evaluation of performance of CD4 count laboratories. The aim of this study was to assess the quality of CD4count laboratory performance using in-house Proficiency testing panels that perform routine CD4 counts in Addis Ababa, Ethiopia, 2013/14., Methods: Participating laboratories were 20, 23 and 25 in trials 1, 2 and 3, respectively. In-house prepared fresh whole blood samples both with "normal" and "low" CD4 values were sent to participating laboratories. Percentage and absolute counts of CD4+ T-lymphocytes were done using their routine procedures. Data were analyzed for each trial including trimmed mean, standard deviation (SD), percent coefficient of variation (%CV), residual, and standard deviation index (SDI) values for both absolute counts and percentages of CD4+ lymphocytes (%CD4)., Results: Most participating laboratories produced results that were within 2SD of the mean. Average inter-laboratory precision (trimmed %CV) was 10.87% and 5.14% for CD4 absolute counts and %CD4, respectively. For normal material, the trimmed mean %CV was 9.59% and3.23% for CD4 absolute counts and %CD4, respectively. For low material, the trimmed mean % CV was 12.15% and 7.05% for CD4 absolute counts and %CD4 respectively. BDFACSCount™ users showed the best accuracy and precision as evidenced by longitudinal analysis., Conclusion: This study was found to help facilities in early identifying their gaps with regard to their CD4 count performance and in avoiding the challenges encountered during participation in external EQA providers like the high cost, transportation problem, feedback delay and CD4laboratory coverage.

Background: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm., Setting: United States, Africa, Asia, Europe and Israel, Australia, Latin America., Methods: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression., Results: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4., Conclusions: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

Background: Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression. Nonadherence to ART led to the human Immunodeficiency Virus (HIV) related morbidity and mortality. Moreover, it intensifies the risk of the emerging drug resistant HIV strains. This study aimed to assess the level of ART adherence and to identify its predictive associated factors among people living with HIV/AIDS in Hara Town and its surroundings, North-Eastern Ethiopia., Methods: An institutional facility based cross-sectional study was conducted from April-May 2017. A total of 454 individuals were on ART follow-up in the selected ART-clinic, and only 418 patients were recruited. Bivariate and multivariate logistic regression analyses were carried out to identify associated factors. Odds ratio and 95% Confidence Interval (CI) were calculated to determine the level of significance., Results: The level of ART adherence in the study setting was 300 (71.8%). Participants who had not disclosed their HIV status to their families were 88% less likely to adhere to their ART medication than those who had disclosed their HIV status ((Odds ratio (OR): 0.12, 95%CI:0.05-0.58; p<0.001). On the other hand, participants who had not encountered drug side effects were 2.69 times more likely to adhere to their ART medication than those who had ever encountered drug side effects (OR: 2.69, 95%CI:1.27-5.05; p<0.001)., Conclusion: A very low level of ART adherence was shown in the study population. It was below the recommended good adherence standard. Therefore, patients should get adequate and comprehensive ART adherence counselling before initiation ART treatment and during the follow-up time.

Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals., Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs  ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression., Results: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05)., Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Despite viral suppression and immune response on antiretroviral therapy, people with HIV infection experience excess mortality compared with uninfected individuals. The Veterans Aging Cohort Study (VACS) Index incorporates clinical biomarkers of general health with age, CD4 cell count, and HIV-1 RNA to discriminate mortality risk in a variety of HIV-positive populations. We asked whether additional biomarkers further enhance discrimination., Design and Methods: Using patients from VACS for development and from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for validation, we obtained laboratory values from a randomly selected visit from 2000 to 2014, at least 1 year after antiretroviral therapy initiation. Patients were followed for 5-year, all-cause mortality through September 2016. We fitted Cox models with established predictors and added new predictors based on model fit and Harrell's c-statistic. We converted all variables to continuous functional forms and selected the best model (VACS Index 2.0) for validation in ART-CC patients. We compared discrimination using c-statistics and Kaplan-Meier plots., Results: Among 28 390 VACS patients and 12 109 ART-CC patients, 7293 and 722 died, respectively. Nadir CD4, CD8, and CD4 : CD8 ratio did not improve discrimination. Addition of albumin, white blood count, and BMI, improved c-statistics in VACS from 0.776 to 0.805 and in ART-CC from 0.800 to 0.831. Results were robust in all nine ART-CC cohorts, all lengths of follow-up and all subgroups., Conclusion: VACS Index 2.0, adding albumin, white blood count, and BMI to version 1.0 and using continuous variables, provides improved discrimination and is highly transportable to external settings.

In human immunodeficiency virus-infected patients, antiretroviral therapy suppresses the viral replication, which is followed in most patients by a restoration of CD4+ T cells pool. For patients who fail to do so, repeated injections of exogenous interleukin 7 (IL7) are experimented. The IL7 is a cytokine that is involved in the T cell homeostasis and the INSPIRE study has shown that injections of IL7 induced a proliferation of CD4+ T cells. Phase I/II INSPIRE 2 and 3 studies have evaluated a protocol in which a first cycle of three IL7 injections is followed by a new cycle at each visit when the patient has less than 550 CD4 cells/μL. Restoration of the CD4 concentration has been demonstrated, but the long-term best adaptive protocol is yet to be determined. A mechanistic model of the evolution of CD4 after IL7 injections has been developed, which is based on a system of ordinary differential equations and includes random effects. Based on the estimation of this model, we use a Bayesian approach to forecast the dynamics of CD4 in new patients. We propose four prediction-based adaptive protocols of injections to minimize the time spent under 500 CD4 cells/μL for each patient, without increasing the number of injections received too much. We show that our protocols significantly reduce the time spent under 500 CD4 over a period of two years, without increasing the number of injections. These protocols have the potential to increase the efficiency of this therapy., (© 2018 John Wiley & Sons, Ltd.)

In 2014, 42% of all HIV diagnoses in the East of England were diagnosed late. Individuals unaware of their HIV status will not benefit from lifesaving and infectious-limiting antiretroviral therapy, and they remain at risk of decreased life expectancy and onward transmission of HIV. We sought to identify risk factors associated with late HIV diagnosis in the East of England to inform future HIV testing and prevention strategies relevant to the local population. Data on all HIV infected individuals aged ≥16 years and diagnosed between 2008 and 2014 in the East of England were obtained from the national HIV and AIDS Reporting System. Late diagnosis was defined as CD4 cell count below 350 cells/mm 3 within 91 days of diagnosis. Logistic regression investigated risk factors for late HIV diagnosis. A total of 2469 people were included; 1342 (54%) were late HIV diagnoses. In multivariable analysis risk factors for late diagnosis were: age ≥30 years, originating from WHO regions of South-East Asia or Europe (excluding UK), heterosexual orientation and being diagnosed as an inpatient or by a general practitioner. The odds of late diagnosis significantly reduced every year (OR 0.95, 95% CI 0.90-0.99, p = 0.042). Despite this year-on-year reduction continued high rates suggest future HIV testing and prevention strategies should be informed by local regional epidemiology to allow those at greatest risk to be targeted appropriately.

The present study retrospectively analyses the prevalence of late diagnosis in patients with newly-diagnosed HIV infection in Lodz, Poland from January 2009 to December 2016, and assesses the predictive factors associated with late presenters. Late presentation is defined as a diagnosis of HIV with a CD4 count<350 cells/μL, or the occurrence of an AIDS- defining event, regardless of the CD4 cell count. Two hundred and fifty-nine (62.86%) patients were late presenters, 178 of whom (68.72%) were advanced late presenters (CD4 cell count below 200 cells/μL). Multivariate factors associated with late HIV presentation included referral from physician for HIV testing (OR: 3.95, 95% CI 2.42-6.46), older age (OR: 1.81, 95% CI: 1.38-2.38) and route of HIV transmission. Heterosexual patients (OR 1.98, 95% CI: 1.01-3.90), active drug users (OR: 3.49, 95% CI: 1.63-7.48) and patients who did not report the route of transmission (OR: 4.29, 95%: CI 1.45-12.62) were more likely to present late than MSM subjects. In conclusion, the majority of HIV-infected patients are still diagnosed late. There is a need for expanded testing not only in MSM group, in which HIV prevalence is the highest, but also in intravenous drug users, or among subjects who are heterosexual or from a higher age group.

The sensitivity of Bayesian inferences to non-ignorability is an important issue which should be carefully handled when analyzing incomplete data sets. Generally, sensitivity analysis quantifies the effect that non-ignorability parameter variations have on model outputs or inferences. This sensitivity can be achieved locally around the ignorable model. Previously, some local sensitivity measures to assess the impact of non-ignorable coarsening on Bayesian inferences have been established based on the first-order derivation of the posterior expectations. This may not be adequate to show potential sensitivity when there is a considerable amount of curvature around the ignorable model estimate. Specifically, it becomes more important when the posterior expectation is U-shaped near the ignorable estimate so that the first-order sensitivity index is approximately zero even if the posterior mean might be highly curved around the ignorable model and hence sensitive to the ignorability assumption. In this paper, we present a method for determining the second-order sensitivity to non-ignorability of Bayesian inferences locally around the ignorable model in GLMs which perform equally well when the impact of non-ignorability is locally linear. Calculation of the proposed second-order sensitivity index only requires some posterior covariances of the simple ignorable model and is conducted efficiently and with minimal computational overhead compared with the first-order sensitivity index. To show the need for the second-order sensitivity index as a more precise screening tool, some simulation studies are conducted. Also, the approach is applied to analyze a real data example with CD4 cell counts as an incomplete response variable., (Copyright © 2018 John Wiley & Sons, Ltd.)

Purpose: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/μL in patients with continuous viral suppression and CD4 cell counts >200 cells/μL., Methods: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/μL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/μL were estimated and compared using Cox proportional hazards regression., Results: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/μL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/μL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/μL, patients with initial CD4 count <300 cells/μL had a significantly higher risk of a CD4 count <200 cells/μL. Patients with viral suppression and CD4 counts ≥350 cells/μL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/μL for 48 months., Conclusions: The probability of a CD4 count <200 cells/μL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/μL was very low. These data suggests less frequent monitoring of CD4 counts in these patients., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: Syphilis is a global health concern with an estimated 12 million infections occurring annually. Due to the increasing rates of new syphilis infections being reported in patients infected with HIV, and their higher risk for atypical and severe presentations, periodic screening has been recommended as a routine component of HIV care. We aimed to characterise incident syphilis presentation, serological features and treatment response in a well-defined, HIV-infected population over 11 years., Methods: Since 2006, as routine practice of both the Southern Alberta Clinic and Calgary STI programmes, syphilis screening has accompanied HIV viral load measures every 4 months. All records of patients who, while in HIV care, either converted from being syphilis seronegative to a confirmed seropositive or were reinfected as evidenced by a fourfold increase in rapid plasma reagin (RPR) after past successful treatment, were reviewed., Results: We identified 249 incident syphilis infections in 194 different individuals infected with HIV; 72% were initial infections whereas 28% were reinfections. Half (50.8%) of the infections were asymptomatic and identified only by routine screening. Symptomatic syphilis was more common when RPR titres were higher (p=0.03). In patients with recurrent syphilis infection, a trend was noted favouring symptomatic presentation (62%, p=0.07). All 10 patients with central nervous system (CNS) syphilis involvement presented with an RPR titre ≥1:32. Following syphilis infection, a decline of 42 cells/mm 3 in CD4 (p=0.004) was found, but no significant changes in viral load occurred. No association was found with the stage of syphilis or symptoms at presentation and antiretroviral therapy use, CD4 count or virological suppression., Conclusion: Routine screening of our HIV-infected population identified many asymptomatic syphilis infections. The interaction of HIV and syphilis infection appears to be bidirectional with effects noted on both HIV and syphilis clinical and serological markers., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Quantile regression provides a detailed and robust picture of the distribution of a response variable, conditional on a set of observed covariates. Recently, it has be been extended to the analysis of longitudinal continuous outcomes using either time-constant or time-varying random parameters. However, in real-life data, we frequently observe both temporal shocks in the overall trend and individual-specific heterogeneity in model parameters. A benchmark dataset on HIV progression gives a clear example. Here, the evolution of the CD4 log counts exhibits both sudden temporal changes in the overall trend and heterogeneity in the effect of the time since seroconversion on the response dynamics. To accommodate such situations, we propose a quantile regression model, where time-varying and time-constant random coefficients are jointly considered. Since observed data may be incomplete due to early drop-out, we also extend the proposed model in a pattern mixture perspective. We assess the performance of the proposals via a large-scale simulation study and the analysis of the CD4 count data.

Describe the prevalence and covariates of viral suppression and subsequent rebound among younger (≤29 years old) compared with older adults.A retrospective clinical cohort study; eligibility criteria: documented HIV infection; resident of Canada; 18 years and over; first antiretroviral regimen comprised of at least 3 individual agents on or after January 1, 2000.Viral suppression and rebound were defined by at least 2 consecutive viral load measurements <50 or >50 HIV-1 RNA copies/mL, respectively, at least 30 days apart, in a 1-year period. Time to suppression and rebound were measured using the Kaplan-Meier method and Life Table estimates. Accelerated failure time models were used to determine factors independently associated with suppression and rebound.Younger adults experienced lower prevalence of viral suppression and shorter time to viral rebound compared with older adults. For younger adults, viral suppression was associated with being male and later era of combination antiretroviral initiation (cART) initiation. Viral rebound was associated with a history of injection drug use, Indigenous ancestry, baseline CD4 cell count >200, and initiating cART with a protease inhibitor (PI) containing regimen.The influence of age on viral suppression and rebound was modest for this cohort. Our analysis revealed that key covariates of viral suppression and rebound for young adults in Canada are similar to those of known importance to older adults. Women, people who use injection drugs, and people with Indigenous ancestry could be targeted by future health interventions.

Background: Health-related quality of life (HRQOL) is a patient-centered outcome measure used in assessing the individual's overall functional health status but studies looking at HRQOL as a predictive tool are few. This work examines whether summary scores of HRQOL are predictive of all-cause hospitalization in the US Military HIV Natural History Study (NHS) cohort., Methods: The Short Form 36 (SF-36) was administered between 2006 and 2010 to 1711 NHS cohort members whose hospitalization records we had also obtained. Physical component summary scores (PCSS) and mental component summary scores (MCSS) were computed based on standard algorithms. Terciles of PCSS and MCSS were generated with the upper terciles (higher HRQOL) as referent groups. Proportional hazards multivariate regression models were used to estimate the hazard of hospitalization for PCSS and MCSS separately (models 1 and 2, respectively) and combined (model 3)., Results: The hazard ratios (HR) of hospitalization were respectively 2.12 times (95% CI: 1.59-2.84) and 1.59 times (95% CI: 1.19-2.14) higher for the lower and middle terciles compared to the upper PCSS tercile. The HR of hospitalization was 1.33 times (95% CI: 1.02-1.73) higher for the lower compared to the upper MCSS tercile. Other predictors of hospitalization were CD4 count < 200 cells/mm 3 (HR = 2.84, 95% CI: 1.96, 4.12), CD4 count 200-349 cells/mm 3 (HR = 1.67, 95% CI: 1.24, 2.26), CD4 count 350-499 cells/mm 3 (HR = 1.41, 95% CI: 1.09, 1.83), plasma viral load > 50 copies/mL (HR = 1.82, 95% CI: 1.46, 2.26), and yearly increment in duration of HIV infection (HR = 0.94, 95% CI: 0.93, 0.96) (model 3)., Conclusion: After controlling for factors associated with hospitalization among those with HIV, both PCSS and MCSS were predictive of all-cause hospitalization in the NHS cohort. HRQOL assessment using the SF-36 may be useful in stratifying hospitalization risk among HIV-infected populations.

Early initiation of antiretroviral therapy increases the likelihood of effective immune restoration, quality of life, and greater life expectancy for HIV-infected individuals. We evaluated the evolution of mean CD4+ cells count at diagnosis of HIV/AIDS in Salvador, Brazil from 2002 to 2015. We identified HIV/AIDS patients older than 18 years with diagnosis of HIV infection from 2002 to 2015, who had their first laboratory evaluation at Complexo Hospitalar Prof. Edgard Santos, Federal University of Bahia. Initial mean CD4+ cells count and age, over time were evaluated. A total of 1801 patients randomly selected individuals were included in the analysis. Overall mean CD4+ count at diagnosis in the whole period was 279±265, varying from 191 in 2015 to 334 in 2011. There was no improvement in the immunological status at diagnosis from 2002 to 2015. In addition, a higher frequency of CD4+ cells count<200cells/mL in the last two years was observed. This suggests that the adopted strategies for early diagnosis of HIV/AIDS in Salvador, Brazil, are still ineffective., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4(+)T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4(+)T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4(+)T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4(+)T cell counts <200 cells/μl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95% CI ) of CD4 <200 cells/μl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion: Decreased CD4(+)T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.

Background: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes., Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts <100 cells/µL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identified using Cox regression with backwards elimination (exit P > .1)., Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality., Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up., Clinical Trials Registration: ISRCTN43622374.

Many survival studies have error-contaminated covariates due to the lack of a gold standard of measurement. Furthermore, the error distribution can depend on the true covariates but the structure may be difficult to characterize; heteroscedasticity is a common manifestation. We suggest a novel dependent measurement error model with minimal assumptions on the dependence structure, and propose a new functional modeling method for Cox regression when an instrumental variable is available. This proposal accommodates much more general error contamination than existing approaches including nonparametric correction methods of Huang and Wang (2000, Journal of the American Statistical Association 95, 1209-1219; 2006, Statistica Sinica 16, 861-881). The estimated regression coefficients are consistent and asymptotically normal, and a consistent variance estimate is provided for inference. Simulations demonstrate that the procedure performs well even under substantial error contamination. Illustration with a clinical study is provided., (© 2017, The International Biometric Society.)

Scientific evidence showing the benefits of early initiation of antiretroviral therapy (ART) prompted World Health organization (WHO) to recommend that all persons diagnosed as HIV positive should commence ART irrespective of CD4 count and disease progression. Based on this recommendation, countries should adopt and implement the HIV "Treat All" policy to achieve the UNAIDS 90-90-90 targets and ultimately reach epidemic control. Attaining this goal along the HIV treatment cascade depends on the laboratory to monitor progress and measure impact. The laboratory plays an important role in HIV diagnosis to attain the first 90 and in viral load (VL) and HIV drug resistance testing to reinforce adherence, improve viral suppression, and measure the third 90. Countries in the Caribbean region have endorsed the WHO HIV "Treat all" recommendation; however, they are faced with diminishing financial resources to support laboratory testing, seen as a rate-limiting factor to achieving this goal. To improve laboratory coverage with fewer resources in the Caribbean there is the need to optimize laboratory operations to ensure the implementation of high quality, less expensive evidence-based approaches that will result in more efficient and effective service delivery. Suggested practical and innovative approaches to achieve this include: (1) targeted testing within HIV hotspots; (2) strengthening sample referral systems for VL; (3) better laboratory data collection systems; and (4) use of treatment cascade data for programmatic decision-making. Furthermore, strengthening quality improvement and procurement systems will minimize diagnostic errors and guarantee a continuum of uninterrupted testing which is critical for routine monitoring of patients to meet the stated goal.