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Background: To date, there is no consensus on ideal ways to measure antiretroviral treatment (ART) adherence in resource limited settings. This study aimed to identify markers of poor adherence to ART., Methods: Retrospective data of HIV-positive ART-naïve adults initiating standard first-line ART at Themba Lethu Clinic, Helen Joseph Hospital, Johannesburg, South Africa from April 2004 to December 2011 were analysed. Poisson regression models with robust error variance were used to assessed the following potential markers of poor adherence 'last self-reported adherence, missed clinic visits, mean corpuscular volume (MCV), CD4 count against definition of adherence, suppressed HIV viral load using traditional test metrics'., Results: A total of 11 724 patients were eligible; 1712 (14.6%) had unsuppressed viral load within 6 months after initiating ART. The main marker of poor adherence was a combination of change in CD4 count and MCV; change in CD4 ≥expected and change in MCV <14.5 fL (RR 2.82, 95% CI 2.16-3.67), change in CD4 

Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART-naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire, 4-6 months after ART initiation. 86 % of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin-positive patients were twice as likely to have detectable viral loads (RR 2.32 95 % CI 1.26-4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis-based assay makes it a prime candidate for implementation in resource-limited settings.

While the diagnostic properties of the TB LAM urine assay (LAM) have been well-described, little is known about its predictive and prognostic properties at ART initiation in a routine clinic setting. We describe the predictive and prognostic properties of LAM in HIV-positive patients initiating ART at an urban hospital in Johannesburg, South Africa. Retrospective study of HIV-positive adults (>18 years) who initiated standard first-line ART between February 2012 and April 2013 and had a LAM test at initiation. In HIV-positive patients with no known TB at ART initiation, we assessed the sensitivity, specificity and positive/negative likelihood ratios of LAM to predict incident TB within 6 months of ART initiation. In addition, in patients with a TB diagnosis and on TB treatment <3 months at ART initiation, we measured the CD4 response at 6 months on ART. Of the 274 patients without TB at ART initiation, 65% were female with median CD4 count of 213 cells/mm(3). Among the 14 (5.1%) patients who developed active TB, none were urine LAM +ve at baseline. LAM had poor sensitivity (0.0% 95% CI 0.00-23.2) to predict incident TB within 6 months of initiation. We analyzed 22 patients with a confirmed TB diagnosis at initiation separately. Of these, LAM +ve patients (27%) showed lower CD4 gains compared to LAM negative patients (median increase 103 vs 199 cells/mm(3); p = 0.08). LAM has limited value for accurately predicting incident TB in patients with higher CD4 counts after ART initiation. LAM may help identify TB/HIV co-infected patients at ART initiation who respond more slowly to treatment and require targeted interventions to improve treatment outcomes. Larger studies with longer patient follow-up are needed.

Introduction: Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers., Methods: We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥ 2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤ 400 copies/ml. We used Cox-proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤ 4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria (CD4 <100 cells/mm(3); CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure., Results: We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mm(3), WHO stage III/IV and albumin) and laboratory and clinical follow-up data (drop in haemoglobin, mean cell volume (MCV) <100 fl, CD4 count <200 cells/mm(3), new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score 51.4% had a score ≥ 4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico-immunological criteria or WHO clinical staging to predict virologic failure (sensitivity 57.1% vs. 40.9%, 25.2% and 20.9%, respectively)., Conclusions: Predictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes.

Background: Challenges to HIV care in resource limited settings (RLS) include malnutrition. Limited evidence supports the benefit of nutritional supplementation when starting antiretroviral therapy (ART) in RLS., Methods: Randomized controlled pilot study. HIV-positive ART-naive adults with self-reported weight loss were randomized to receive ART plus FutureLife porridge nutritional supplement (NS) (388 kcal/day) or ART alone (Controls) for 6 months. Patients returned for monthly assessments and blood was drawn at enrolment and 6 months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6 months on treatment., Results: Of the 36 randomized patients, 26 completed the 6 month follow-up (11 NS vs 15 Controls). At enrolment, groups were similar in terms of age, gender, body mass index (BMI) and bioelectrical impedance. NS patients had a lower median CD4 count (60 cells/mm3 [IQR 12-105 vs. 107 cells/mm3 [IQR 63-165]; p = 0.149) and hemoglobin (10.3 g/dL [IQR 9.0-11.3] vs. 13.1 g/dL [IQR 11.1-14.7]; p = 0.001)., Conclusion: Preliminary results are encouraging and suggest that NS taken concurrently with ART can promote weight gain, improve immune response and improve physical activity in HIV-positive patients that present at ART initiation with weight loss.

Background: Treatment outcomes for antiretroviral therapy (ART) patients may vary by gender, but estimates from current evidence may be confounded by disease stage and adherence. We investigated the gender differences in treatment response among HIV-positive patients virally suppressed within 6 months of treatment initiation., Methods: We analyzed data from 7,354 patients initiating ART between April 2004 and April 2010 at Themba Lethu Clinic, a large urban public sector treatment facility in South Africa. We estimated the relations among gender, mortality, and mean CD4 response in HIV-infected adults virally suppressed within 6 months of treatment initiation and used inverse probability of treatment weights to correct estimates for loss to follow-up., Results: Male patients had a 20% greater risk of death at both 24 months and 36 months of follow-up compared to females. Older patients and those with a low hemoglobin level or low body mass index (BMI) were at increased risk of mortality throughout follow-up. Men gained fewer CD4 cells after treatment initiation than did women. The mean differences in CD4 count gains made by women and men between baseline and 12, 24, and 36 months were 28.2 cells/mm(3) (95% confidence interval [CI] 22.2-34.3), 60.8 cells/mm(3) (95% CI 71.1-50.5 cells/mm(3)), and 83.0 cells/mm(3) (95% CI 97.1-68.8 cells/mm(3)), respectively. Additionally, patients with a current detectable viral load (>400 copies/mL) and older patients had a lower mean CD4 increase at the same time points., Conclusions: In this initially virally suppressed population, women showed consistently better immune response to treatment than did men. Promoting earlier uptake of HIV treatment among men may improve their immunologic outcomes.

Objective: To estimate loss to follow up (LTFU) between initial enrollment and the first scheduled return medical visit of a pre-antiretroviral therapy (ART) care program for patients not eligible for ART., Methods: The study was conducted at a public-sector HIV clinic in Johannesburg. We reviewed records of all patients newly enrolled in the pre-ART care program and not yet eligible for ART between January 2007 and February 2008. Crude proportions of patients completing their first return medical visit stratified by patient characteristics were calculated. A modified-Poisson approach was used to estimate directly relative risks of returning for their first return medical visit within 1 year adjusting for patient characteristics as potential confounders., Results: A total of 356 patients were identified. Two-thirds had a CD4 count > 350 cells/microl (median [IQR] CD4 = 458 [394, 585]) and were scheduled to return in 6 months for a first medical visit. Seventy-four percent of these patients did not return within one year for this visit. The remaining 36% of all patients had a baseline CD4 count 251-350 cells/microl and were scheduled to return in 3 months. Only 6% of these patients returned within 4 months; 41% returned within one year. Relative risks were positively associated with a patient being employed and negatively associated with the baseline CD4 count., Conclusions: Given the high rate of LTFU immediately after enrolling in pre-ART care, it is clear that care programs are not expediting the timely initiation of ART. Significantly improved adherence to pre-ART care and monitoring for patients not yet eligible for ART is required for South Africa to achieve its AIDS strategy goals and reduce the problem of late presentation and initiation of ART.

There are approximately 33 million individuals with HIV infection worldwide. The majority of infections are in southern Africa where hepatitis B is also known to be endemic. As access to life-saving antiretroviral therapy (ART) increases, the possibility for hepatitis B treatment resistance increases because most ART regimens contain lamivudine. Patients coinfected with HBV are therefore receiving monotherapy for HBV infection, leading to possible HBV-resistant mutants and the concurrent public health effect thereof. Additional information is needed on the prevalence of HIV-HBV coinfection and treatment response to ART. We present a summary of the information available from South Africa to date.