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This paper presents an innovative Bayesian method for assessing the status and progression of HIV infection using biomarkers such as the CD4 count and viral load variables. A distribution of viral loads in subjects starting antiretroviral treatment and followed over time may show a mixture of two subgroups: one subgroup representing "non-progressor" subjects and another subgroup of "progressor" subjects. In modeling these groups, we use a mass point and a right-skewed continuous distribution in which trajectories of repeated observations of viral load exhibit multiphasic features along with a gradual transition period. The commonly used method for describing these phasic patterns is a bent-cable model with a quadratic function for modeling the gradual transition phase. A quadratic function may be too restrictive for adequately modeling the transition period. Thus, we we extend the bent-cable model within the context of a two-component Tobit growth model by relaxing the assumption of a quadratic function for a gradual transition period and accounting for measurement errors in CD4 count. The proposed methods are demonstrated using real data from an AIDS clinical study. [ABSTRACT FROM AUTHOR]

In this paper, we provide a unified framework for two-sample t-test with partially paired data. We show that many existing two-sample t-tests with partially paired data can be viewed as special members in our unified framework. Some shortcomings of these t-tests are discussed. We also propose the asymptotically optimal weighted linear combination of the test statistics comparing all four paired and unpaired data sets. Simulation studies are used to illustrate the performance of our proposed asymptotically optimal weighted combinations of test statistics and compare with some existing methods. It is found that our proposed test statistic is generally more powerful. Three real data sets about CD4 count, DNA extraction concentrations, and the quality of sleep are also analyzed by using our newly introduced test statistic. [ABSTRACT FROM AUTHOR]

In this paper, we assess the effect of tuberculosis pericarditis treatment (prednisolone) on CD4 count changes over time and draw inferences in the presence of missing data. We accounted for the missing data and performed sensitivity analyses to assess robustness of inferences, from a model that assumes that the data are missing at random, to models that assume that the data are not missing at random. Our sensitivity approaches are within the shared-parameter model framework. We implemented the approach by Creemers and colleagues to the CD4 count data and performed simulation studies to evaluate the performance of this approach. We also assessed the influence of potentially influential subjects, on parameter estimates, via the global influence approach. Our results revealed that inferences from missing at random analysis model are robust to not missing at random models and influential subjects did not overturn the study conclusions about prednisolone effect and missing data mechanism. Prednisolone was found to have no significant effect on CD4 count changes over time and also did not interact with anti-retroviral therapy. The simulation studies produced unbiased estimates of prednisolone effect with lower mean square errors and coverage probabilities approximately equal the nominal coverage probability. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the effect of tuberculosis pericarditis (TBP) treatment on CD4 count changes over time and draw inferences in the presence of missing data. We accounted for missing data and conducted sensitivity analyses to assess whether inferences under missing at random (MAR) assumption are sensitive to not missing at random (NMAR) assumptions using the selection model (SeM) framework. We conducted sensitivity analysis using the local influence approach and stress-testing analysis. Our analyses showed that the inferences from the MAR are robust to the NMAR assumption and influential subjects do not overturn the study conclusions about treatment effects and the dropout mechanism. Therefore, the missing CD4 count measurements are likely to be MAR. The results also revealed that TBP treatment does not interact with HIV/AIDS treatment and that TBP treatment has no significant effect on CD4 count changes over time. Although the methods considered were applied to data in the IMPI trial setting, the methods can also be applied to clinical trials with similar settings. [ABSTRACT FROM AUTHOR]

Introduction:Pneumocystispneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART),Pneumocystispneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis forPneumocystispneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: ‘Pneumocystispneumonia’, ‘Pneumocystis jiroveciipneumonia’, ‘Pneumocystis carinii pneumonia’, ‘trimethoprim-sulfamethoxazole’, ‘primaquine’, ‘trimetrexate’, ‘dapsone’, ‘pentamidine’, ‘atovaquone’, ‘echinocandins’, ‘human immunodeficiency virus infection’, ‘acquired immunodeficiency syndrome’, ‘resistance to sulfamide’ and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent forPneumocystispneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles forPneumocystispneumonia is warranted. [ABSTRACT FROM PUBLISHER]

HIV and AIDS has serious repercussions on psychological, social and physical well-being, and the assessment of Quality of Life (QoL) of people living with HIV and AIDS is essential to gauge how these challenges are met. The WHOQoL-HIV Bref forms part of a suite of instruments developed by the World Health Organisation. The purpose of this paper is to describe the quality of life of a sample of HIV-infected students at a South African university, as well as explain the internal consistency between questions within each of the QoL domains. A descriptive, cross-sectional study design using a quantitative approach was applied. A non-probability, purposive sampling approach was utilized and students enrolled in the antiretroviral therapy or wellness programme were invited to voluntarily participate in this study. The WHOQOL-HIV Bref was self-administered after explanation of the questions by a registered, trained health care professional. A total of 63 students returned completed questionnaires that were included in the analysis. Acceptable to good reliability scores were established for the following domains: Level of Independence; Social Relations; Environment and Spiritual or Personal Beliefs. Assessing QoL in the sample, the lowest score was for “Spirituality” and the highest “Social Relations”. The “Physical” and “Psychological” domain scores for females were significantly lower than the score for males. There was no significant difference between any of the domain scores among participants with CD4 cell counts above or below 350 cells/mm3. In general the performance of this sample is encouraging and it is recommended that the measure be utilized for QoL screening, and further research. The WHOQOL-HIV Bref for students does not contain an academic wellness component which should be added considering the significant effects of HIV on neuropsychological functioning. Also further investigation into the reasons for poor scores obtained in physical and psychological well-being in females should be encouraged. [ABSTRACT FROM PUBLISHER]

Unannounced phone-based pill counts (UPC) are an objective measure of medication adherence that may be used in resource limited settings. The current study reports the feasibility and validity of UPC for monitoring antiretroviral therapy (ART) adherence among people living with HIV in South Africa. People living with HIV (N = 434) in an economically impoverished township and receiving ART for at least 3-months completed: two UPC in a one-month period; measures of clinic and medication experiences; and provided blood samples for HIV viral load and CD4 testing. Analyses compared two methods for managing values of over-dosing (> 100%), specifically censoring values to 100% (> 100% = 100%) vs. subtracting over-dosing from two months of perfect adherence (200% - > 100% value). Findings showed that two UPC calls were successfully completed with 91% of participants in a one-month period. The average number of call attempts needed to reach participants was 2.4. Results showed that lower UPC adherence was significantly associated with male gender, alcohol use, higher HIV viral loads, lower CD4 cell counts, running out of ART, and intentionally not taking ART. Comparisons of methods for adjusting over-dosing found subtraction yielding a better representation of the data than censoring. UPC were demonstrated feasible and valid with patients receiving ART in a resource limited setting and offers a viable method for objectively measuring ART adherence in these settings. [ABSTRACT FROM AUTHOR]

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up. Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present. Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27–59, p < 0.001), followed by high CD4/CD8 ratio (41%, 21–57, p < 0.001) and lower physical activity (32%, 95% CI 5–52, p = 0.03). PAF was not significant for daily caloric intake (−1%, −9-13, p = 0.45), smoking cessation during follow-up (5%, 0–12, p = 0.10), INSTI switch (11%, −19-36; p = 0.34). Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI. [ABSTRACT FROM AUTHOR]

In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors. [ABSTRACT FROM PUBLISHER]

For persons living with HIV/AIDS, the relationship between stress and clinical outcomes has received little attention in current research, yet represents an important area for future research and intervention. Chronic illness has been theorized to place additional demands on a person that may exceed their ability to cope with daily life, leading to long-term stress, which then increases the risk for negative health outcomes in persons already at risk. This paper reviews the existing global literature to answer two main questions: (1) how is stress conceptualized in research with persons living with HIV/AIDS? and (2) what are the current findings linking stress to clinical outcomes? Twenty-three articles are included in the final review. Findings reveal that researchers conceptualize stress in multiple ways for persons living with HIV/AIDS, including depressive symptomology, post-traumatic stress, life events, emotions linked to stress, and biological markers (such as cortisol levels and autonomic nervous system activity). Further, findings related to the link between stress and clinical outcomes are mixed; however, stress was shown to be related to lower CD4 cell counts, higher viral load, and disease progression. Several studies also showed a link between stress and poorer treatment adherence. Implications and directions for future research are discussed, including further thought into how we conceptualize stress for persons living with HIV, future research that is necessary to elucidate current mixed findings on the link between stress and clinical outcomes, and preliminary suggestions for intervention to prevent and alleviate stress in this population. [ABSTRACT FROM PUBLISHER]

An important marker for identifying the progression of human immunodeficiency virus (HIV) infection in an individual is the CD4 cell count. Antiretroviral therapy (ART) is a treatment for HIV/AIDS (AIDS, acquired immune-deficiency syndrome) which prolongs and improves the lives of patients by improving the CD4 cell count and strengthen the immune system. This strengthening of the immune system in terms of CD4 count, not only depends on various biological factors, but also other behavioral factors. Previous studies have shown the effect of CD4 count on the mortality, but nobody has attempted to study the factors which are likely to influence the improvement in CD4 count of patients diagnosed of AIDS and undergoing ART. In this paper, we use Poisson regression model (GPR) for exploring the effect of various socio-demographic covariates such as age, gender, geographical location, and drug usage on the improvement in the CD4 count of AIDS patients. However, if the CD4 count data suffers from under or overdispersion, we use GPR model and compare it with negative binomial distribution. Finally, the model is applied for the analysis of data on patients undergoing the ART in the Ram Manohar Lohia Hospital, Delhi, India. The data exhibited overdispersion and hence, GPR model provided the best fit. [ABSTRACT FROM PUBLISHER]

This study estimated the efficiency of implementing the EmERGE Pathway of Care for people living with medically stable HIV in Brighton, UK; an App enables individuals to communicate with caregivers via their smart-phone. Individual data on the use of HIV outpatient services were collected one-year pre- and post-implementation of EmERGE. Unit costs of HIV outpatient services were calculated and linked with mean use of services per patient year. Primary outcomes were CD4 count and viral load; patient activation and quality-of-life measures were secondary outcomes. 565 participants were followed up April 2017 - October 2018: 93% men, mean age at recruitment 47.0 years (95%CI:46.2–47.8). Outpatient visits decreased by 9% from 5.6 (95%CI:5.4-5.8) to 5.1 (95%CI:4.9-5.3). Face-to-face visits decreased and virtual visits increased. Annual costs decreased by 9% from £751 (95%CI: £722-£780) to £678 (95%CI: £653-£705). Including anti-retroviral drugs, total annual cost decreased from £7,343 (95%CI: £7,314–7,372) to £7,270 (95%CI: £7,245–7,297): ARVs costs comprised 90%. EmERGE was a cost-saving intervention, patients remained engaged and clinically stable. Annual costs were reduced, but ARVs continue to dominate costs. Extension of EmERGE to other people with chronic conditions, could produce greater efficiencies but these needs to be evaluated and monitored over time. [ABSTRACT FROM AUTHOR]

For people living with HIV (PLWH) who are subsequently diagnosed with non-Hodgkin lymphoma (NHL), we investigate the impact of standard-of-care (SoC) cancer treatment on all-cause, NHL-specific, and HIV-specific survival outcomes. The focus is on a registry-derived, population-based sample of HIV + adults diagnosed with NHL within 2004–2012 in the state of Georgia. SoC treatment is defined as receipt of multi-agent systemic therapy (MAST). In multivariable survival analyses, SoC cancer treatment is significantly associated with better all-cause and NHL-specific survival, but not better HIV-specific survival across 2004–2017. Having a CD4 count <200 near the time of cancer diagnosis and Ann Arbor stage III/IV disease are associated with worse all-cause and HIV-specific survival; the effects on NHL survival trend negative but are not significant. Future work should expand the geographic base and cancers examined, deepen the level of clinical detail brought to bear, and incorporate the perspectives and recommendations of patients and providers. [ABSTRACT FROM AUTHOR]

Longitudinal count and time to event (TTE) data are often associated in some ways. Hence, using joint models for analyzing these data constitutes an attractive modeling framework which is applied in many different fields of statistics and clinical studies. Also, Accelerated Failure Time (AFT) models can be used for the analysis of TTE data to estimate the effects of covariates on acceleration/deceleration of the survival time. So, we assume that the time variable is modeled in this article with Weibull AFT distribution. Furthermore, to develop the joint modeling strategy of these kinds of data, a correlated generalized linear mixed effect model (GLMEM) is applied using a member of the family of power series (PS) distributions in the longitudinal count submodel. Both of longitudinal count and TTE data may have excess zeros. The adequate of this approach in joint modeling with considering two censoring mechanism, right and left is illustrated using some simulation studies. Finally, we implement these proposed joint models on real AIDS data set. [ABSTRACT FROM AUTHOR]

Among people who inject drugs (PWID), 60% have HCV and 50–90% of HIV-infected PWID are co-infected with HCV. Data comparing adherence to direct-acting antiviral (DAA) therapy among HCV mono-infected and HIV/HCV co-infected PWID is limited. The impact of HCV treatment initiation on HIV antiretroviral therapy (ART) adherence is also poorly understood. We assessed DAA adherence in HCV mono-infected and HIV/HCV co-infected PWID and examined changes in ART adherence and HIV outcomes following HCV treatment. Study was conducted in three Medication for Opioid use Disorder (MOUD) programs in Bronx, New York. HCV treatment adherence was measured using electronic blister packs. 2-week DAA adherence rates were compared and controlled for study arm, psychiatric illness and alcohol intoxication within the past 30 days. ART adherence was measured using participant self-report and dichotomized to "excellent" or "other". ART adherence, CD4 count, and HIV viral load were identified six months prior to, during, and six months after HCV treatment. Statistical significance was assessed with mixed-effects regression linear or logistic models. Overall DAA adherence rates among HCV mono-infected and HIV/HCV co-infected PWID were 74% (95% CI=71–78%) and 76% (95%CI=70–83%), respectively (p=.55). There were no significant changes in ART adherence, CD4 counts, or HIV viral loads prior to, during, or after HCV treatment. This is the first study assessing the impact of DAA therapy on ART adherence and HIV treatment outcomes among PWID. It is one of the first to compare DAA adherence among HCV and HIV/HCV co-infected PWID. Our data demonstrate no significant difference in DAA adherence and no significant impact of HCV treatment on ART adherence or HIV outcomes. [ABSTRACT FROM AUTHOR]

HIV infection causes a constant activation of the immune system and contributes to an enhanced systemic pro-inflammatory cytokine milieu, which has been associated with premature aging and frailty. We performed a systematic review and meta-analysis to analyze whether the HIV-1 RNA load, CD4+ T-lymphocyte counts and exposure to HAART in HIV-positive subjects are associated with frailty phenotype. Searches were performed in PubMed, SCOPUS, Lilacs, Web of Science, Google Scholar, and OpenThesis databases. We used the odds ratio as a measure of the association. We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. Eleven studies were included in the review. Data from 8035 HIV-positive subjects were analyzed; 2413 of the subjects had viral load detectable, 981 had a CD4T-cell count <350 cells/μL, and 1342 had HAART exposure information. We found an association between frailty and CD4T-cell count <350 cells/μL (OR 2.68, CI 95% 1.68–4.26, I2 = 46%), HIV-1 RNA load detectable (OR 1.71, CI 95% 1.38–2.12, I2 = 0%), and protease inhibitor-containing HAART regimen (OR 2.21, CI 95% 1.26–3.89, I2 = 0%). Further studies are necessary to evaluate the effects of other factors on the development of clinical features related to frailty. [ABSTRACT FROM AUTHOR]

Studies describing characteristics and outcomes of COVID-19 among people living with HIV are currently limited, lacking detailed evaluation of the interplay among demographics, HIV-related variables, and comorbidities on COVID-19 outcomes. This retrospective cohort study describes mortality rates overall and according to demographic characteristics and explores predictors of admission to intensive care unit and death among 255 persons living with HIV with severe acute respiratory syndrome and confirmed SARS-CoV-2 infection in the State of Sao Paulo, Brazil. We found that the overall mortality rate was 4.1/1,000 person-days, with a case-fatality of 34%. Higher rates occurred among older adults, Black/Mixed skin color/race patients, and those with lower schooling. In a multivariable analysis adjusted for age, sex, CD4 count, viral load and number of comorbidities, skin color/race, and schooling remained significantly associated with higher mortality. Although tenofovir use was more frequent among survivors in the univariable analysis, we failed to find a statistically significant association between tenofovir use and survival in the multivariable analysis. Our findings suggest that social vulnerabilities related to both HIV and COVID-19 significantly impact the risk of death, overtaking traditional risk factors such as age, sex, CD4 count, and comorbidities. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) reduces HIV replication to undetectable levels and prevents AIDS but cannot cure the infection and discontinuing ART results in viral rebound. Therefore, a primary goal of HIV therapeutic vaccine research is to induce potent HIV-specific immunity that could control viremia without ART, a so-called "functional cure" that eliminates the need for lifelong ART. DNA vaccines have several features that make them an attractive modality for an HIV therapeutic vaccine: they are easy to manufacture, induce T-cell and antibody responses without anti-vector immunity, and do not involve ex vivo manipulations of patient cells. This review covers the progress in developing therapeutic HIV DNA vaccines, emphasizing delivery innovations to enhance vaccine immunogenicity. A central theme is a transition from needle injection delivery to the muscle toward using more sophisticated devices to target the skin and/or increasing transfection efficiency. There are multiple barriers to an effective therapeutic HIV DNA vaccine. While variables such as delivery, adjuvants, and immunogen design have been extensively explored, combining DNA vaccines with complementary approaches is underdeveloped. Complementary approaches include co-administration with latency reversal agents, immune checkpoint blockade, and targeting conserved fitness-constrained portions of the virus. [ABSTRACT FROM AUTHOR]

To our knowledge, no published literature has focused on South Asians living with HIV in the U.K. since 2004. We reviewed the case-notes of all patients self-identifying as South Asian attending two HIV centres in North East London between 1st January and 31st December 2017. Of 131 patients, 107 were male, median age 43 (range 24–72). Most (73.3%) were born outside the U.K., 55.7% were Muslim. 56.5% identified as heterosexual. However, 5.4% of heterosexual men may have become infected from sex between men. More men who have sex with men (MSM) (59.6%) were diagnosed on routine screening rather than when symptomatic or through partner notification, compared to heterosexual men (30.6%) and women (48.0%). Heterosexual men and women were diagnosed with lower CD4 counts than MSM (257 vs 307 vs 456 cells/µL).. Almost all of the sample were on antiretroviral treatment (97.7%), of whom 94.5% had an undetectable viral load (<200 copies/ml). The cohort was highly co-morbid (60.3%) and 38.9% had a history of poor mental health. We describe a diverse sample of British South Asians living with HIV We recommend that culturally specific campaigns encouraging routine HIV testing in the British South Asian population should be developed. [ABSTRACT FROM AUTHOR]

Machine Learning (ML) can improve the analysis of complex and interrelated factors that place adherent people at risk of viral rebound. Our aim was to build ML model to predict RNA viral rebound from medication adherence and clinical data. Patients were followed up at the Swiss interprofessional medication adherence program (IMAP). Sociodemographic and clinical variables were retrieved from the Swiss HIV Cohort Study (SHCS). Daily electronic medication adherence between 2008–2016 were analyzed retrospectively. Predictor variables included: RNA viral load (VL), CD4 count, duration of ART, and adherence. Random Forest, was used with 10 fold cross validation to predict the RNA class for each data observation. Classification accuracy metrics were calculated for each of the 10-fold cross validation holdout datasets. The values for each range from 0 to 1 (better accuracy). 383 HIV+ patients, 56% male, 52% white, median (Q1, Q3): age 43 (36, 50), duration of electronic monitoring of adherence 564 (200, 1333) days, CD4 count 406 (209, 533) cells/mm3, time since HIV diagnosis was 8.4 (4, 13.5) years, were included. Average model classification accuracy metrics (AUC and F1) for RNA VL were 0.6465 and 0.7772, respectively. In conclusion, combining adherence with other clinical predictors improve predictions of RNA. [ABSTRACT FROM AUTHOR]

Background: The screening strategy for HIV-Associated Neurocognitive Disorders (HAND) is challenging. The French Expert Report recommend the use of the Cognitive Complaints Questionnaire (QPC) and the Montreal Cognitive assessment. However, the QPC has never been studied in People Living with HIV (PLWH). This study aims to determine the degree of agreement between QPC and the presence of HAND according to Frascati criteria, established by a battery of neuropsychological tests. Methods: Data from patients who performed both a QPC and a battery of neuropsychological tests over a six-month follow-up period were evaluated retrospectively. Results: A total of 121 patients were selected, with a median age of 53.1 years old. Among participants, 92.6% had an undetectable plasma viral load, 49.6% had a nadir CD4 less than 200/mm3 and 23.1% had a CDC stage C. Median CD4 cell count was 686/mm3. Prevalence of HAND was 57%, including 28.9% of Asymptomatic Neurocognitive Impairment, 24.8% of Mild Neurocognitive Disorder and 3.3% of HIV-associated Dementia. This analyze shows no agreement between QPC and HIV-associated neurocognitive disorders (kappa = −0.007). Conclusions: The QPC is not relevant in the screening for HAND. Thus, it urges to develop a specific tool to assess cognitive complaints among PLWH. [ABSTRACT FROM AUTHOR]

Little is known about how CD4 and viral load testing have evolved following implementation of universal test and treat (UTT) in African settings. We reviewed World Health Organization (WHO) guidance from 2013 to 2018, and compared it against national HIV policies in Malawi, Tanzania and South Africa. Three surveys rounds were conducted in 2013, 2016 and 2017–2018 in 33 health facilities across the three settings to assess implementation of national policies on the use of biological markers. Qualitative interviews were conducted with 26 HIV policymakers or programme managers, 21 providers and 66 people living with HIV to explore understandings and experiences of these tests. Various factors influenced adoption and implementation of WHO guidance, including historical policies on CD4 counts, governance issues, supply chain challenges and funding mechanisms. Facility-level practices relating to the use of these tests often diverged from national policies. Patients and providers valued both tests, but did not always understand their roles. In addition to continued support for scaling-up viral load testing, renewed focus should be placed on the ongoing value of point-of-care CD4 tests in the UTT era, including its role in assessing disease progression and informing clinical management of cases to reduce HIV-related mortality. [ABSTRACT FROM AUTHOR]

The conventional survival analysis model on HIV/AIDS prognosis is the Cox proportional hazard model, which deals with only one event type, death, regardless of the cause. Few studies have used a competing risk model to evaluate the predictors of AIDS-related mortality. To estimate the influence of antiretroviral therapy (ART) initiation time and baseline CD4+ cell counts on acquired immunodeficiency syndrome (AIDS)-related death among former plasma donors. A retrospective cohort study was conducted involving 11,905 human immunodeficiency virus (HIV) or AIDS patients in a high-risk area of Henan province in China between 1995 and 2016. Demographic and clinical data were collected. Sub-distribution hazard ratios (sHRs) for AIDS-related mortality with baseline CD4+ cell counts and ART initiation time were determined using a competing risk model. Patients who initiated ART within 90 days of HIV/AIDS diagnosis (sHR: 0.24, 95% CI: 0.22–0.27) or had baseline CD4+ counts of >500 cells/μL (sHR: 0.23, 95% CI: 0.19–0.28) were associated with lower AIDS-related mortality risk. Patients with ART initiation time >1 year but CD4+ counts >350 cells/μL (sHR: 4.42, 95% CI: 3.30–5.91) had a higher AIDS-related mortality risk than those with ART initiation time >90 days but CD4+ counts ≤350 cells/μL (sHR: 4.33, 95% CI: 3.58–5.23). Our results demonstrate that patients with high CD4+ cell counts and late ART had a 9% higher risk of AIDS-related death than those with low CD4+ cell counts and early ART. This study confirms the great significance of immediate ART initiation among former plasma donor HIV patients in China. [ABSTRACT FROM AUTHOR]

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated in AMBER (treatment-naïve adults; NCT02431247) and EMERALD (treatment-experienced, virologically-suppressed adults; NCT02269917). To describe a Week 96 pre-planned subgroup analysis of D/C/F/TAF arms by demographic characteristics (age ≤/>50 years, gender, black/non-black race), and baseline clinical characteristics (AMBER: viral load [VL], CD4+ count, WHO clinical stage, HIV-1 subtype and antiretroviral resistance; EMERALD: prior virologic failure [VF], antiretroviral experience, screening boosted protease inhibitor [PI], and boosting agent). Patients in D/C/F/TAF and control arms could continue on/switch to D/C/F/TAF in a single-arm, open-label extension phase after Week 48 until Week 96. Efficacy endpoints were percentage cumulative confirmed VL ≥50 copies/mL (virologic rebound; EMERALD), and VL <50 (virologic response), or ≥50 copies/mL (VF) (FDA snapshot; both trials). D/C/F/TAF demonstrated high Week 96 virologic responses (AMBER: 85% [308/362]; EMERALD: 91% [692/763]) and low VF rates (AMBER: 6% [20/362]; EMERALD: 1% [9/763]). In EMERALD, D/C/F/TAF showed low virologic rebound cumulative through Week 96 (3% [24/763]). Results were consistent across subgroups, including prior antiretroviral experience in EMERALD. No darunavir, primary PI, or tenofovir resistance-associated mutations were observed post-baseline. Study-drug-related serious adverse events (AEs) and AE-related discontinuations were <1% and 2%, respectively (both D/C/F/TAF arms), and similar across subgroups. eGFRcyst and bone mineral density improved or were stable and lipids increased through Week 96 across demographic subgroups, with small changes in total-cholesterol/HDL-cholesterol ratio. D/C/F/TAF was effective with a high barrier to resistance and bone/renal safety benefits, regardless of demographic or clinical characteristics for treatment-naïve and treatment-experienced, virologically-suppressed adults. [ABSTRACT FROM AUTHOR]

Purpose: The role of HIV infection in exogenous and endogenous endophthalmitis has not been clarified. We aim to assess the potential role of HIV as a risk factor or a poor prognostic feature in this sight-threatening condition. Methods: Literature review. Review of evidence: Evidence for endophthalmitis in HIV patients is based on scarce retrospective case series and case reports. Infrequency of literature on this topic is owed to the diversity of the different types of endophthalmitis as well as the rarity of the coexistence of the two conditions. Conclusions: Endophthalmitis in HIV patients are a rare but potentially devastating condition. Many forms of endophthalmitis tend to occur in severely immunosuppressed HIV patients with low CD4 counts. Therefore, the early introduction of cART with full immune reconstitution is an essential part of the prevention of endophthalmitis in the HIV population. [ABSTRACT FROM AUTHOR]

Combination Antiretroviral Therapy (cART) in single-tablet regimens (STR) is a simplification strategy that can potentially improve medication adherence and clinical outcomes. We conducted a retrospective cohort study of 1206 patients using efavirenz, tenofovir and lamivudine in multiple-tablet regimen who switched to the STR containing the same active ingredients in a southeast metropolis in Brazil. We measured adherence using the proportion of days covered (PDC≥95%) and evaluated this outcome before and after the switch using paired non-parametric statistics. Additionally, we used group-based trajectory modeling to identify adherence patterns to cART for each period and evaluate the migration behavior of patients between the trajectory groups. We observed a 14% increase in the proportion of adherent patients after switching to STR and a 6.2% increase in the proportion of patients with CD4 count>500 cells/μl (p < 0.001), without changes in viral load outcomes. We identified four adherence trajectories in each period. Most patients (60%, n = 722) migrated towards a group with better adherence trajectory or remained in the trajectory group with the highest probability of adherence after the switch. Our findings suggest that the implementation of the STR had a positive impact on adherence and CD4 count. This may potentially improve virologic outcomes later on treatment. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm3 than in the control group. It became clear that the patients taking anti-HIV drugs, especially the CD4+ count < 500/mm3 group, had a deteriorated oral environment and dysgeusia, suggesting that the management of oral hygiene is necessary to maintain oral health, which leads to systemic health. [ABSTRACT FROM AUTHOR]

This article examines the adaptation and biomedical transition of people living with HIV (PLHIV) to antiretroviral treatment (ART) in Burkina Faso. The study employs a representative sample of 3625 randomly selected patients. Subjective and objective measures of health and their predictors are compared for short-term (≤24 months) versus longer-term ART adherents (>24 months) in a cohort study. Subjective health is measured as Likert scale self-rating and objective health as CD4 count. The results show that subjective and objective health capture different aspects of adaptation to ART: 90% of the short-term and 94% of the longer-term patients give a subjective health rating of at least good, while the objective measure of good health is higher among longer-term (42%) compared to short-term patients (27%). For subjective health, short-lived pleasures are predictors among short-term adherents while economic characteristics are determinants among longer-term patients. Meanwhile, objective health is associated with factors that determine ART adherence (i.e. participating in self-help groups). To achieve a wholistic resilience management that caters to the needs of PLHIV, we need to acknowledge adaptation to the disease and to ART and design health programs, in particular in developing countries, away from one-size-fits-all solutions to stage-of-disease specific support. [ABSTRACT FROM AUTHOR]

We conducted a population-based study of biologic, clinical, and sociodemographic factors associated with receipt of multi-agent systemic therapy (MAST) by people living with HIV (PLWH) who were diagnosed with non-Hodgkin lymphoma (NHL). Building on recent registry-based analyses, we linked records from the Georgia Cancer Registry, Georgia HIV/AIDS Surveillance Registry, and the Georgia Hospital Discharge Database to identify 328 PLWH adults (age ≥ 18) diagnosed with NHL within 2004–2012. Through logistic regression modeling, we examined factors associated with patients receiving MAST for NHL. Robust predictors included CD4 count ≥200 cells/mm3 around the time of cancer diagnosis, an advanced stage (III or IV) diagnosis of NHL, MSM HIV transmission, and having private health insurance. The strongest single predictor of MAST was CD4 count. Because there is now guideline-integrated evidence that PLWH receiving standard-of-care cancer therapy can achieve substantially improved outcomes, it is vital they have access to regimens routinely provided to HIV-negative cancer patients. [ABSTRACT FROM AUTHOR]

Antiretroviral therapies have been tested with the goal of maintaining virological suppression with a particular attention in limiting drug-related toxicity. With this aim we designed the DUAL study: a randomized, open-label, multicenter, 96 weeks-long pilot exploratory study in virologically suppressed HIV-1+ patients with the aim of evaluating the immunovirological success and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). We recruited patients who received a PI/r-containing HAART for ≥6 months, HIV-RNA < 50 cp/mL for ≥3 months, eGFR > 60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV + DRV/r QD or arm B: ongoing triple therapy. The primary endpoint has been defined as the percentage of patients with HIV-RNA < 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP (uRBP) were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Forty-one patients were enrolled (22 in arm A, 14 in arm B, plus 5 screening failures): 30 patients reached 96 weeks: 100% had HIV-RNA < 50 cp/mL in arm A versus 91.7% in arm B. Similar changes were observed in median CD4/mL between baseline and week 96 (+59 versus − 31, p: n.s.). Thirty-one in arm A and 23 in arm B adverse events took place, whereas only 1 was serious (arm A: turbinate hypertrophy, unrelated to HAART). Among the 6 discontinuations (3 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). VACS index, median FRS and median uRBP values did not vary from baseline to week 96. At 96-weeks all patients switched to a QD 2-drug regimen based on DRV/r + RPV maintained HIV-RNA suppression, but a single patient who showed a virological failure at week 4. CD4 counts increased overtime without significant differences between the two arms. The novel dual regimen was well tolerated with the same amount of discontinuation as the control arm. VACS index, FRS and uRBP did not differ between arms at week 96. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the presenting features of cytomegalovirus (CMV) retinitis in HIV-positive patients in a developing country in the HAART era.Methods: Retrospective chart review of all patients with CMV retinitis seen at a tertiary-care referral center between January 2006 to June 2017. Demographic and clinical data were collected to study the presenting features and risk factors for blindness.Results: Fifty-five patients with treatment-naïve CMV retinitis were enrolled; 75% were males. CD4 counts were below 50 cells/µL in 51.1%. Bilateral presentation was seen in 61.5%. Half (50.6%) of the eyes were blind at first examination. Zone 1 involvement was present in 46% of the eyes. Retinal area involvement > 25% was the only factor associated significantly with higher incidence of blindness (p = 0.016).Conclusions: There was extensive and bilateral presentation of CMV retinitis due to delayed presentation. Screening for CMV retinitis, irrespective of CD4 counts, may help in developing nations. [ABSTRACT FROM AUTHOR]

The World Health Organisation (WHO) recommends antiretroviral treatment (ART) initiation at human immunodeficiency virus (HIV) diagnosis. As ART programmes expand, addressing barriers to adherence is vital. Past mixed findings on the association between social support, stigma and non-disclosure with ART adherence highlights the need for further research. The primary aim of this study was to examine how these factors are associated with ART non-adherence in the six months after ART initiation. The secondary aim was to explore how other factors are associated with non-adherence. We conducted secondary analysis of prospective data from HIV-positive adults initiating ART. Social support, disclosure patterns, perceived stigma and other demographic factors were collected at ART initiation and six months follow-up. Logistic regression models were used to examine factors associated with self-reported ART non-adherence in the last six months and the last month before the six month follow-up ("recent"). Non-adherence in the last six months was twenty-five percent and recent non-adherence was nine percent. There was no association between non-adherence and social support, stigma or non-disclosure of HIV status. In the final model the odds of non-adherence in the last six months were significantly higher for those: with incomplete ART knowledge (aOR 2.10, 95%CI 1.21–3.66); who visited a healthcare provider for conditions other than HIV (aOR1.98, 95%CI 1.14–3.43); had higher CD4 counts at ART initiation (CD4 100–199:aOR 2.50, 95%CI 1.30–4.81; CD4 ≥ 200:aOR 2.85, 95%CI 1.10–7.40;referent CD4 < 100 cells/mm3); had tested HIV-positive in the last year (aOR 2.00, 95%CI 1.10–3.72; referent testing HIV-positive outside the last year); experienced a rash/itching secondary to ART (aOR 2.48, 95%CI 1.37–4.52); and significantly lower for those ≥48 years (aOR 0.65, 95%CI 0.46–0.90). Early non-adherence remains a concern. Incorporation of adherence monitoring and ART knowledge enhancement into appointments for ART collection may be beneficial. [ABSTRACT FROM AUTHOR]

The START Study randomly assigned 4685 persons with CD4+ counts >500 to either immediate treatment (2326 persons) or a group (2359) that had treatment delayed until the CD4+ count was <350 or clinical judgment dictated treatment. The average time in the study was three years. The immediate group (IG) had 42 serious clinical events and the delayed group (DG) had 96. Policy considerations for adopting these results should consider the cost of medications for early treatment, which is the purpose of this article. Cost of early treatment was estimated by assuming the delayed treatment group had been treated for the three-year average course of the study. However, 48% of the DG received ART before the study's end, so that portion of the group's time on ART was reduced to 1.5 years. Average wholesale prices in the United States of the five recommended ART regimens were discounted by 50% to reflect actual pricing. An average medication cost for the five regimens of $20,000 per person year was used. The three-year cost was $107,580,000 for the 52% who would have been treated for three years and for the 48% treated for an average of 1.5 years. The cost per clinical event avoided was $1,992,222. Formulae are provided that will allow the reader to adjust these results to reflect local prices and volumes. Additional factors to be considered should include the cost savings from avoiding serious clinical events, reduction in transmission of HIV for those being treated early in the infection and the issues associated with long-term adherence for those receiving ART at >500 CD4 counts [ABSTRACT FROM AUTHOR]

Objectives: A cross-sectional study was undertaken at Lancers Road Clinic, Durban, South Africa to determine body composition, haemoglobin, serum albumin and serum high sensitivity C-reactive protein (hs-CRP) levels in asymptomatic ART-naive HIV positive adults. Methods: All eligible adults attending the clinic were sampled. Body composition was assessed using deuterium dilution. Descriptive statistics, Wilcoxon rank-sum test, chi-square test, Fisher’s exact test and Spearman’s rank correlation coefficient were used for data analysis. Results: A total of 84 participants (CD4 count: 542.5 ± 145 cell/mm3) enrolled. The mean body mass index (BMI) was 29.5 (± 6.4) kg/m2 and the mean fat mass percentage was 44.9 (± 18.7). The prevalence of overweight (26.2%, 22/84) and obesity (46.4%, 39/84) was high. Mean haemoglobin (Hb) levels were 12.0 ± 1.6 g/dl. Mild, moderate and severe anaemia was present in 21.4% (18/84), 20.2% (17/84) and 1.2% (1/84) of patients, respectively. Mean albumin levels (36.2 ± 3.8 g/l) were on the borderline low range of normal with mildly depleted albumin levels being present in a third (32.1%, 27/84) of patients. The mean hs-CRP levels (5.5 ± 7.2 mg/l) were high. Conclusion: In this cohort of patients, wasting was not associated with HIV as the prevalence of overweight/obesity was high and followed the population trend in SA. This seemingly well, asymptomatic population of people living with HIV was at an increased risk of morbidity, progression and death due to the compounding factors of overweight/obesity, hypoalbuminemia, raised hs-CRP levels and anaemia. [ABSTRACT FROM AUTHOR]

Progressive decline in CD4 cell counts is associated with human immunodeficiency virus (HIV) disease progression. Loss of CD4 cells might contribute to gut microbiota alteration and bacterial translocation. Probiotics, by inducing epithelial healing, may promote the restoration of the intestinal CD4+ T-cell population. The aim of this meta-analysis was to systematically review all randomized controlled trials (RCTs) of probiotic/prebiotic/synbiotic supplementation on CD4 cell counts in HIV-infected patients. A systematic search of RCTs was conducted through PubMed, Scopus, and Google Scholar databases up to August 2015. Effect sizes of eligible studies were pooled using random-effects models (the DerSimonian-Laird estimator). Eleven studies with 14 treatment arms met the inclusion criteria. Pooled analysis showed no significant reduction in CD4 counts (−7.5 mg/l, p =.7) in intervention-treated individuals. Subgroup analysis on potential influencing factors highlighted sex, country of origin, study duration, and the type of intervention as having significant effects on CD4 cell counts. As a whole, the results of this meta-analysis suggested that supplementation with probiotic may not change CD4 counts. However, a significant increase in CD4 counts was seen in females and following synbiotics as opposed to treatment with pro- or prebiotics alone. [ABSTRACT FROM AUTHOR]

Introduction: Despite active antiretroviral therapy (ART), community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients and incurs high health costs. Areas covered: This article reviews the most recent publications on bacterial CAP in the HIV-infected population, focusing on epidemiology, prognostic factors, microbial etiology, therapy, and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline, and references from relevant articles. Expert commentary: HIV-infected patients are more susceptible to bacterial CAP. Although ART improves their immune response and has reduced CAP incidence, these patients continue to present increased risk of pneumonia in part because they show altered immunity and because immune activation persists. The risk of CAP in HIV-infected patients and the probability of polymicrobial or atypical infections are inversely associated with the CD4 cell count. Mortality in HIV-infected patients with CAP ranges from 6% to 15% but in well-controlled HIV-infected patients on ART the mortality is low and similar to that seen in HIV-negative individuals. Vaccination and smoking cessation are the two most important preventive strategies for bacterial CAP in well-controlled HIV-infected patients on ART. [ABSTRACT FROM AUTHOR]

We use a socioecological model of health to define resilience, review the definition and study of resilience among persons living with human immunodeficiency virus (PLWH) in the existing peer-reviewed literature, and discuss the strengths and limitations of how resilience is defined and studied in HIV research. We conducted a review of resilience research for HIV-related behaviors/outcomes of antiretroviral therapy (ART) adherence, clinic attendance, CD4 cell count, viral load, viral suppression, and/or immune functioning among PLWH. We performed searches using PubMed, PsycINFO and Google Scholar databases. The initial search generated 14,296 articles across the three databases, but based on our screening of these articles and inclusion criteria, n = 54 articles were included for review. The majority of HIV resilience research defines resilience only at the individual (i.e., psychological) level or studies individual and limited interpersonal resilience (e.g., social support). Furthermore, the preponderance of HIV resilience research uses general measures of resilience; these measures have not been developed with or tailored to the needs of PLWH. Our review suggests that a socioecological model of health approach can more fully represent the construct of resilience. Furthermore, measures specific to PLWH that capture individual, interpersonal, and neighborhood resilience are needed. [ABSTRACT FROM AUTHOR]

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission. [ABSTRACT FROM AUTHOR]

For patients with AIDS receiving antiretroviral treatment (ART) in South Africa via public clinics, improvements in nutritional status and economic productivity are likely to depend on adherence to drug regimen and quality of diet reflected in protein and micronutrient intakes. This study randomized 643 patients receiving ART from public clinics in the Free State Province into a Control group, a treatment group receiving adherence support, and a treatment group receiving adherence support and a nutritious food supplement. The data on food insecurity levels and time spent on various activities were analyzed for assessing the impact of the intervention programs. The main results were, first, changes between survey rounds 1 and 3 were significant at the 5% level for outcomes such as food insecurity levels and CD4 cell counts. Moreover, there was a significant reduction in food insecurity levels of patients with BMI less than 25 who received the nutritious food supplement. Second, the estimated parameters from models for patients' food insecurity levels showed that household incomes were significantly associated with lower food insecurity levels. Third, patients' BMI was a significant predictor of time spent on sedentary, moderate and overall activity levels, and it was important to separately evaluate the effects of BMI for under-weight and over-weight patients. Overall, the results indicated the need for reducing food insecurity levels, and for designing different interventions for under-weight and over-weight patients with AIDS for enhancing their labor productivity. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the immunologic profile in aqueous humor (AqH) of HIV-infected individuals with cytomegalovirus retinitis (CMVr) or ocular syphilis and to assess if AqH and plasma represent independent cytokine compartments.Methods: Concentrations of 27 cytokines in AqH and plasma of HIV-infected individuals with CMVr (n = 23) or ocular syphilis (n = 16) were measured by multiplex assay. Cytokine profiles of both groups were compared.Results: Individuals with CMVr had higher plasma concentrations of interleukin (IL)-7, IL-8, IL-10, interferon (IFN)-γ, IFN-α2, G-CSF, IP-10 and IL-1α; as well as higher AqH concentrations of IL-1α, IP-10 and GM-CSF than those with ocular syphilis. AqH and plasma levels correlated only for IP-10 in both ocular infections.Conclusions: Individuals with CMVr had higher plasma cytokine levels than those with ocular syphilis. The immunologic profiles in AqH and plasma are independent. Therefore, AqH cytokine concentrations cannot be inferred from plasma cytokine concentrations in the population studied. [ABSTRACT FROM AUTHOR]

Studies on the effects of alcohol use on HIV disease progression have been contradictory, with at least one study finding a positive effect of low alcohol consumption on CD4 count. In addition, most such studies have taken place in the developed West. We investigated the association between alcohol use and immune reconstitution through CD4 count response among HIV-infected individuals on antiretroviral therapy (ART) at an urban sub-Saharan African clinic. This was a retrospective cohort study of treatment-naïve HIV-infected adults initiating ART in Nairobi, Kenya and followed for 12 months between January 2009 and December 2012. At enrollment, a standardized questionnaire was used to collect data on sociodemographic variables and alcohol consumption. CD4 count was measured every six months. Linear regression models assessed the association between CD4 count and alcohol consumption, categorized as abstinent, moderate, or hazardous. Overall, 854 participants were included, 522 of which were women, with 85 (25.6%) men and 50 (9.6%) women reporting any alcohol use, and 8 (2.4%) men and 7 (1.3%) women reporting hazardous drinking. At baseline, alcohol use was associated with higher education and socioeconomic status. Median CD4 count was higher among alcohol users compared to those who abstained at baseline and at 6 and 12 months post-ART initiation, although this was only significant at 6 months. There were no differences in adherence between abstainers and drinkers. While overall alcohol use was significantly associated with higher CD4 counts, moderate and hazardous use treated separately were not. We conclude that, while alcohol use was associated with higher CD4 counts at 12 months post-ART, the mechanism for this association is unclear but may reflect unmeasured socioeconomic or nutritional differences. Additional research is required on the specific drinking patterns of this population and the types of alcoholic beverages consumed to clarify this relationship. [ABSTRACT FROM AUTHOR]

Psychological stress is a known immunomodulator. In individuals with HIV, depression, the most common manifestation of increased psychological stress, can affect immune function with lower CD4+ T cell counts correlating with higher levels of depression. It is unknown how other forms of psychological stress can impact immune markers in people living with HIV. We conducted a cross-sectional study to determine how CD4+ T cell subpopulations correlated with different forms of psychological stress. We recruited 50 HIV-positive women as part of the Women’s Interagency HIV Study. We assessed perceived stress, worry, acute anxiety, trait anxiety, and depression through self-report questionnaires and CD4+ T cell subpopulations using flow cytometry. Our sample was 96% African-American with a mean ± SD age and body mass index of 42 ± 8.8 years and 36.6 ± 11.5 kg/m2, respectively. The mean ± SD scores on the psychological measures were as follows: Perceived Stress Scale (PSS), 16.5 ± 6.4; Penn State Worry Questionnaire (PSWQ), 47.7 ± 13.8; State-Trait Anxiety Inventory – State (STAIS), 39.1 ± 12.3; State-Trait Anxiety Inventory – Trait (STAIT), 40.2 ± 11.4; Center for Epidemiological Studies Depression Scale (CES-D), 15.6 ± 11.4. The mean + SD values for the immune parameters were as follows: regulatory T cells (Treg), 1.25% ± 0.7; T helper 1 (Th1), 14.9% ± 6.1; T helper 2 (Th2), 3.8% ± 2; Th1/Th2 ratio, 4.6 ± 3; and CD4+ T cell count (cells/mm3), 493 ± 251. Treg levels positively correlated with PSS, STAIS, and STAIT. CD4+ T cell count negatively correlated with PSS, PSWQ, STAIS, STAIT, and CES-D. These data suggest that immune function may be impacted by various forms of psychological stress in HIV-positive women. Interventions that target stress reduction may be useful in improving immune parameters and quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To report the use of flow cytometry on aqueous fluid to diagnose sarcoidosis in a patient with recurrent granulomatous anterior uveitis.Methods: Case report.Results: Flow cytometry on aqueous fluid demonstrated a CD4/CD8 ratio >9.5, consistent with a diagnosis of sarcoidosis.Conclusions: Flow cytometry on aqueous fluid may offer an additional pathway for diagnosing sarcoid anterior uveitis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the surgical outcomes, complications and postoperative progression in HIV patients undergoing cataract surgery in a teaching hospital.Methods: A retrospective cohort study of patients with HIV/AIDS who had cataract surgery from January 2000 until December 2011 at a tertiary referral multidisciplinary hospital in Singapore.Results: We identified 44 eyes from 29 patients. Preoperatively, 41.3% had no ophthalmic manifestations of HIV/AIDS, while 16 eyes had quiescent cytomegalovirus retinitis (CMVR). Postoperatively, 1 eye developed new CMVR, while 1 eye had reactivation of previous CMVR. Of eyes with new or previous CMVR, 1 eye developed rhegmatogenous retinal detachment (RD) postoperatively. Only 3 eyes had prolonged postoperative inflammation. There were no cases of endophthalmitis or cystoid macular edema. Postoperative improvement of at least two Snellen lines was achieved in 86.6% of eyes.Conclusions: Cataract surgery in HIV patients is generally safe, regardless of CD4 count, but their general and ocular health should be optimized preoperatively. [ABSTRACT FROM AUTHOR]

Purpose: To compare changes in the demographic profile and ocular manifestations in patients with HIV in the pre-HAART and HAART era in North India.Methods: In this single-center cross-sectional study, 100 HIV patients receiving HAART and 96 HIV patients in the pre-HAART era were enrolled. Prevalence of ocular manifestations of HIV was calculated for both cohorts.Results: The prevalence of ocular manifestations was not statistically different in the two eras (38%, SE: 4.85% in HAART era; 41.67%, SE: 5% in pre-HAART era) (p = 0.60). Mean CD4 counts were lower in the pre-HAART era compared with the HAART era (p < 0.001). In the HAART era, cytomegalovirus (CMV) retinitis and HIV retinopathy continued to remain the most common infectious and non-infectious cause of visual morbidity.Conclusions: While the introduction of HAART has resulted in a major impact on the overall health of patients with HIV, the spectrum of ocular disease remains largely unchanged in developing countries such as India. [ABSTRACT FROM AUTHOR]

Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients’ response of less than “all-of the time” to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of <95% medication possession ratio (MPR). Logistic regression models were fitted to identify factors associated with sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count. [ABSTRACT FROM PUBLISHER]

For the treatment of HIV, compliance in regard to appointment attendance and medication usage is critical. Various methods have been attempted to increased HIV care compliance, and a method that has inspired many published studies is text message reminders. We conducted a meta-analysis of the literature from inception through May 2016 using the following databases: Pubmed, Embase, CINAHL, Web of Science, and Cochrane. Examples of terms used in the search included exploded versions of “HIV, “AIDS”, “cell phone”, “SMS”, “text message”, “reminder”. After abstract and manuscript review, articles were discussed with co-author and included based on consensus. We excluded qualitative analyses, observational studies without an intervention, and studies without a control or pre-intervention group. We used random-effects models to calculate odds ratios (OR) and standardized mean differences (SMDs) for the text message intervention. Thirty-four unique studies were found and included in the meta-analysis. For the seven articles relating to non-attendance, text message reminders significantly reduced the rates of non-attendance (OR, 0.66; 95% CI, 0.48–0.92;P = .01;I2 = 52%). For the 20 articles on drug adherence, text message reminders significantly increased adherence (SMD, 0.87; 95% CI, 0.06–1.68;P = .04;I2 = 99%). For the 11 articles with physiologic measures (CD4 count or viral load), text message reminders led to significant improvement (SMD, 1.53; 95% CI, 0.52–2.55;P = .003;I2 = 99%). This meta-analysis reveals that text message reminders are a promising intervention that can be used to increase HIV care compliance when logistically feasible. Further study should focus on which populations benefit the most from this intervention, and successful implementers could create an established technological infrastructure for other clinics to adopt when seeking to boost compliance. [ABSTRACT FROM PUBLISHER]

Introduction: Antiretroviral treatment of HIV infection reduces, but does not eliminate, viral replication and down modulates immune activation. The persistence of low level HIV replication in the host, nevertheless, drives a smouldering degree of immune activation that is observed throughout the natural history of disease and is the main driving force sustaining morbidity and mortality. Areas covered: Early start of antiretroviral therapy (ART) and intensive management of behavioural risk factors are possible but, at best, marginally successful ways to manage immune activation. We review alternative, possible strategies to reduce immune activation in HIV infection including timing of ART initiation and ART intensification to reduce HIV residual viremia; switch of ART to newer molecules with reduced toxicity; use of anti inflammatory/immunomodulatory agents and, finally, interventions aimed at modifying the composition of the microbiota. Expert commentary: Current therapeutic strategies to limit immune activation are only marginally successful. Because HIV eradication is currently impossible, intensive studies are needed to determine if and how immune activation can be silenced in HIV infection. [ABSTRACT FROM AUTHOR]

Food insecurity is defined as a limited or uncertain ability to acquire acceptable foods in socially acceptable ways, or limited or uncertain availability of nutritionally adequate and safe foods. While effective antiretroviral treatment can significantly increase CD4 counts in the majority of patients, there are certain populations who remain at relatively low CD4 count levels. Factors possibly associated with poor CD4 recovery have been extensively studied, but the association between food insecurity and low CD4 count is inconsistent in the literature. The objective is to systematically review published literature to determine the association between food insecurity and CD4 count among HIV-infected people. PubMed, Web of Science, ProQuest ABI/INFORM Complete, Ovid Medline and EMBASE Classic, plus bibliographies of relevant studies were systematically searched up to May 2015, where the earliest database coverage started from 1900. Studies that quantitatively assessed the association between food insecurity and CD4 count among HIV-infected people were eligible for inclusion. Study results were summarized using random effects model. A total of 2093 articles were identified through electronic database search and manual bibliographic search, of which 8 studies included in this meta-analysis. Food insecure people had 1.32 times greater odds of having lower CD4 counts compared to food secure people (OR = 1.32, 95% CI: 1.15–1.53) and food insecure people had on average 91 fewer CD4 cells/µl compared to their food secure counterparts (mean difference = −91.09, 95% CI: −156.16, −26.02). Food insecurity could be a potential barrier to immune recovery as measured by CD4 counts among HIV-infected people. [ABSTRACT FROM PUBLISHER]