BACKGROUND:We investigated whether serum levels of biomarkers of inflammation, immune activation, and angiogenesis, which have been implicated in the pathogenesis of Kaposi sarcoma (KS), were associated with tumor burden and treatment response of advanced AIDS-KS. METHODS:Participants with advanced, previously untreated AIDS-KS enrolled in AMC066/ACTG A5263, a prospective, randomized trial conducted in sub-Saharan Africa and South America, were randomly assigned to either paclitaxel (PTX)+ART or bleomycin/vincristine (BV)+ART. Biomarkers of inflammation (C-reactive protein, IL-6, IL-8, IL-10, G-CSF, sTNF-RII), immune activation (sCD25/sIL-2Rα, CXCL10/IP-10, CCL2/MCP1), and angiogenesis (MMP-9, soluble endoglin, vascular endothelial growth factor, MMP-2, and hepatocyte growth factor) were measured by Luminex to determine whether pre- or post-treatment levels were associated with KS response and tumor burden. Wilcoxon rank-sum tests were used to compare biomarkers levels between groups. RESULTS:One hundred thirty-one participants met the analysis inclusion criteria (70 PTX, 61 BV; 82 nonprogressors, 49 progressors). Higher baseline KS tumor burden was associated with higher pretreatment inflammatory and immune activation biomarker levels, and lower levels of markers with angiogenesis-inhibitory activity. Associations of baseline biomarker levels with subsequent KS response were not observed; however, progressors showed higher levels of several markers of inflammation and immune activation (IL-6, IL-10, sTNF-RII, and IP-10) than nonprogressors at weeks 3 and 12. CONCLUSIONS:Pretreatment biomarker levels were associated with greater KS tumor burden but not with KS response to chemotherapy + ART in people with advanced AIDS-KS. Differential levels of several serum biomarkers were noted on treatment in progressors and nonprogressors, suggesting that increased tumor burden was associated with higher levels of inflammation and immune activation.

Background Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. Methods In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. Findings 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. Interpretation Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. Copyright (c) 2020 Elsevier Ltd. All rights reserved.

Background:We previously reported Kaposi sarcoma-associated herpesvirus (KSHV) microRNA sequence variants in clinical samples correlated with increased risk of multicentric Castleman's disease (MCD). We then demonstrated that microRNAs with variant sequence have different maturation and mature microRNA expression in vitro. Here, we illustrate the association between microRNA sequence and changes in mature microRNA levels within Kaposi sarcoma (KS) lesions.Methods:KSHV microRNA sequences were determined from 20 KS lesions and 4 control skin biopsies from individuals evaluated for KS. Levels of mature KSHV microRNAs were measured with 21 custom small RNA qRT-PCR assays using RNA RNU6B as endogenous control.Results:The levels of 13 KSHV-encoded microRNAs were elevated in KS lesions compared to control biopsies. MicroRNA 9-5p was strongly down regulated in South African vs. US biopsies. Low levels of K12-9-5p were associated with single nucleotide polymorphisms (SNPs) in miR-K12-9-5p, 4-5p, 5-3p, 7-3p and pri-miR-K12-3. One SNP in pri-miR-K12-3 resulted in down regulation of miR-K12-6-3p, 8-3p, 10-3p, 12-5p and the upregulation of 5-5p, illustrating sequence variants outside pre-microRNAs were also associated with changes in mature microRNA levels.Conclusions:The levels of mature KSHV-encoded microRNAs in KS lesions correlate with sequence variation reflecting changes in secondary and tertiary RNA structure.

Purpose The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. Participants The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. Findings to date Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. Future plans Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa.

Background: Chronic inflammation, possibly exacerbated by cigarette smoking, is considered to be the primary cause of pulmonary damage in patients with tuberculosis (TB). However, the mechanisms which underpin these harmful inflammatory responses, have not been well documented. Objectives: The current study was undertaken to determine possible associations between systemic biomarkers of inflammation (acute phase reactants, stress hormones, leukocyte vitamin C) and smoking status in patients (n=71, 20 smokers) with newly-diagnosed pulmonary TB presenting at a tertiary hospital, Johannesburg, South Africa. Methods: Plasma concentrations of C-reactive protein (CRP), ferritin, cortisol, epinephrine, norepinephrine, dopamine and leukocyte vitamin C were measured using a combination of immunonephelometric, radioimmunoassay, immunochromatographic and spectrophotometric procedures. Demographic, clinical and laboratory data was captured and analysed by parametric and non-parametric analyses where appropriate. Results: Smokers were predominantly males (P<0.0001), of older age (P<0.0003) with a significantly lower body mass index (P<0.03). Plasma levels of CRP, ferritin and dopamine were higher in the group of smokers in the setting of lower levels of epinephrine, and leukocyte vitamin C, with CRP and vitamin C attaining statistical significance (P<0.04 and P<0.02 respectively). Those of cortisol and norepinephrine were comparable to those of non-smokers, as were radiographic changes and clinical indices of disease activity. Conclusion: Cigarette smoking is associated with an exaggerated systemic inflammatory response in pulmonary TB in the setting of decreased concentrations of leukocyte vitamin C. Although no significant associations with radiographic changes and most clinical indices of disease activity were evident on presentation, these pro-inflammatory interactions may have prognostic significance.

The world of iron metabolism has been taken over by molecular biology. The astounding progress over the past ten years would be nowhere had it not had a solid foundation built on years of careful research and observation. One of the pioneers in laying this foundation was Thomas Hamilton Bothwell. He entered the field just as a new technology was becoming available: radioactivity. His first paper, which set him off on a career in iron research, was not merely a case report on a patient with haemochromatosis but ‘radioiron studies in a case of haemochromatosis’ and was published in no lesser forum than the prestigious Journal of Laboratory and Clinical Medicine. It was fortuitous that this young patient presented with cardiac failure and so came to the attention of the budding cardiologist. Just as the researchers of today are exploiting technologies evolved from the polymerase chain reaction, so Bothwell used radioiron to delve into the mysteries of iron absorption, iron loss and ‘internal iron exchange’ – how iron is recycled and put to use again and again. Bothwell has produced over 300 publications, the vast majority on aspects of iron metabolism, and in most of his original articles, radioiron has been the essential research tool.

Background: Host genetic factors may a play role in susceptibility to infection. Vitamin-D is an immunomodulator that may play a role in HIV infection. Vitamin-D action is mediated by the vitamin-D receptor. We establish prevalence of ApaI, BsmI, FokI and TaqI polymorphisms (VDRPs) amongst a black southern African HIV+ve population and investigate polymorphic differences between HIV+ve and -ve people. Methods: Seventy-nine sex and age-group matched HIV+ve patients of African origin initiating antiretroviral therapy (ART) and 79 HIV-ve participants, also of African origin, were recruited from a public sector HIV testing and treatment clinic and investigated for the 4 polymorphisms. The genotype frequencies were compared, odds ratios and 95% confidence intervals of the association of HIV status and each genotype were calculated. Both dominant, co-dominant, recessive and allele models were tested. Results: We found no evidence of difference in distribution and association between HIV infection and the genotypes of the BsmI, FokI and TaqI VDR polymorphisms. The genotype distributions were consistent with Hardy-Weinberg equilibrium for these genotypes. The ApaI genotype showed differences in distribution by HIV status in the dominant and co-dominant models. However this finding is cautiously stated as the ApaI genotype violated the Hardy-Weinberg equilibrium and frequency of the minor variant was unexpectedly low in this population. Conclusion: We do not show convincing differences in distribution of the VDR genotypes among HIV+ve and HIV-ve black southern African persons. Future studies need to be replicated in larger study populations as understanding polymorphic differences and similarities may offer insights into the different susceptibility and progression of HIV in southern African populations.

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

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.

Background: Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12months after initiation of ART.Methods: We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment.Results: Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm(3)) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm(3)) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06) within the first 6-months of treatment.Conclusions: HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.

Objectives: South African HIV care providers are exploring ways to reduce the intensity of patient visits while maintaining high quality of care. We used routinely collected data to model whether a simple screening tool could identify stable patients who would not need to see a doctor during a scheduled medical visit.Design: We identified stable and nonstable visits from January 2007 to September 2011 at a large HIV clinic in Johannesburg, SA. Stable medical visits were defined as having all of the following: stable CD4 count, undetectable viral load, stable weight, not pregnant, no comorbidity, no regimen change within three months, and normal laboratory results for hemoglobin, alanine aminotransferase, and creatinine clearance.Methods: We assessed the sensitivity and specificity of nonstable visits at predicting indicators of disease progression or needing additional care: (1) ART regimen change and (2) follow-up visits in <2 and <4 weeks from previous visit.Results: Stable visits had a sensitivity of 88.9% (95% confidence interval: 88.2 to 89.7) and a specificity of 44.8% (44.5 to 44.1) at predicting ART therapy changes, and a sensitivity of 72.6% (71.8 to 73.4) and specificity of 45.1% (44.8 to 45.4) for predicting a followup visit interval of <2 weeks and similar results for predicting a follow-up visit interval of <4 weeks.Conclusions: Our retrospective analysis suggests an approach to potentially reduce the number of medical visits while missing few visits in which changes in regimen or additional care would be needed. Evaluation of our criteria in a primary care setting is needed to determine whether they could safely reduce visits.

The Themba Lethu Clinical Cohort was established in 2004 to allow large patient-level analyses from a single HIV treatment site to evaluate National Treatment Guidelines, answer questions of national and international policy relevance and to combine an economic and epidemiologic focus on HIV research. The current objectives of the Themba Lethu Clinical Cohort analyses are to: (i) provide cohort-level information on the outcomes of HIV treatment; (ii) evaluate aspects of HIV care and treatment that have policy relevance; (iii) evaluate the cost and cost-effectiveness of different approaches to HIV care and treatment; and (iv) provide a platform for studies on improving HIV care and treatment. Since 2004, Themba Lethu Clinic has enrolled approximately 30 000 HIV-positive patients into its HIV care and treatment programme, over 21 000 of whom have received anti-retroviral therapy since being enrolled. Patients on treatment are typically seen at least every 3 months with laboratory monitoring every 6 months to 1 year. The data collected include demographics, clinical visit data, laboratory data, medication history and clinical diagnoses. Requests for collaborations on analyses can be submitted to our data centre.

Background: The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa.Methods: We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation.Results: Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment.Conclusions: In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.

OBJECTIVES:Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients.METHODS:Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed.RESULTS:A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism.CONCLUSIONS:These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF.

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 (95% confidence interval [CI] 22.2–34.3), 60.8 cells/mm (95% CI 71.1-50.5 cells/ mm), and 83.0 cells/mm (95% CI 97.1-68.8 cells/mm), 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.

Coding Guide Example: MOAA01 (Weekday) MO (Session type) AA (Session order) 01 Weekdays: SU (Sunday), MO (Monday), TU (Tuesday), WE (Wednesday), TH (Thursday), FR (Friday) Session types: oral abstract sessions AA (Track A), AB (Track B), AC (Track C), AD (Track D), AE (Track E), AX (Cross-Track), LBA (Late Breaker Track A), LBB (Late Breaker Track B), LBC (Late Breaker Track C), LBD (Late Breaker Track D), LBE (Late Breaker Track E), LBX (Late Breaker Cross-Track); oral poster discussions sessions PDA (Track A), PDB (Track B), PDC (Track C), PDD (Track D), PDE (Track E) PDX (Cross-Track) Session order: 01, 02, 03, 04, etc. Abstracts of the XIX International AIDS Conference Journal of the International AIDS Society 2012, 15 (Suppl 3) Track C Epidemiology and Prevention Science

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.