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We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic.

The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy.

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Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups.

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Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration.

Background WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited.Methods We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg.Results Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23–71), CD4 percentage was 27.9 (19.2–38.0), and weight was 4.0 kg (3.0–4.7) at ART initiation. In those with ≥1 month’s follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5–39.5). Abacavir discontinuations did not differ by age or weight category (p= 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10–0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p= 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p= 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0–3.2).Conclusion Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.

Supplemental Digital Content is available in the text

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As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status.

Antiretroviral therapy reduces the risk of tuberculosis, but tuberculosis is more common in people with HIV than in people without HIV. We aimed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy.

Background There is debate over using tenofovir or zidovudine alongside lamivudine in second-line anti-retroviral therapy (ART) following stavudine failure. We analysed outcomes in cohorts from South Africa, Zambia and ZimbabweMethods Patients aged =16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programmes in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models. Its parameters were estimated using inverse probability of treatment weights. Baseline characteristics were age, sex, calendar year and country. CD4+T-cell count, creatinine and haemoglobin levels were included as time-dependent confounders.Results A total of 1,256 patients on second-line ART, including 958 on tenofovir, were analysed. Patients on tenofovir were more likely to have switched to second-line ART in recent years, spent more time on first-line ART (33 versus 24 months) and had lower CD4+T-cell counts (172 versus 341 cells/ml) at initiation of second-line ART. The adjusted hazard ratio comparing tenofovir with zidovudine was 1.00 (95% CI 0.59, 1.68) for virological failure and 1.40 (0.57, 3.41) for death.Conclusions We did not find any difference in treatment outcomes between patients on tenofovir or zidovudine; however, the precision of our estimates was limited. There is an urgent need for randomized trials to inform second-line ART strategies in resource-limited settings.

Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa.

Public sector antiretroviral provision had a slow start in South Africa despite a raging epidemic and a World AIDS conference that shed significant public light on the disparities of therapy access globally. This was largely due to political prevarication in the midst of AIDS denialism. There has been an unprecedented expansion in the HIV treatment programme since 2008. As a result, South Africa now has the largest number of patients on antiretroviral drugs in the world, and South African life expectancy has increased by more than a decade. However, this has led to a number of fiscal, logistic and operational challenges that the country must face as the treatment programme continues to expand. Challenges include increasing detection within communities, linkage and retention in care, while strengthening operational support functions such as consistent drug supply, health staffing and infrastructure, diagnostic services, programme monitoring and sustainable financing. As a middle-income country, albeit with marked income inequality, and the heaviest HIV burden in the world, South Africa is a test case of whether a large-scale public health programme can boast of success in the face of numerous other health-system challenges.

Robust evidence of the effectiveness of task shifting of antiretroviral therapy (ART) from doctors to other health workers is scarce. We aimed to assess the effects on mortality, viral suppression, and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) programme, which provides educational outreach training of nurses to initiate and represcribe ART, and to decentralise care.

In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.

A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings.

We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa.

Finding ways to reduce the high rates of sexual partner concurrency is increasingly believed to be vital to controlling HIV spread in southern Africa. We describe the frequency and correlates of sexual partner concurrency in a representative sample of 3 324 young South Africans aged 14–25. Of the 2 468 individuals who were sexually active 21% had engaged in concurrent sexual partnerships. Multivariate analysis revealed that concurrency was more common with males, Africans, those who knew their partner had another partner, early age of sexual debut, four or more lifetime sexual partners, alcohol consumption, and self-perception of being at high risk for acquisition of HIV. If the respondent's partner knew his or her friends (termed high structural embeddedness) this was associated with a 52% reduction in concurrency rates. There are significant differences in both the rates of concurrency and the risk factors underpinning these in the different racial/ethnic groups. Analysis of these underlying determinants suggests that cultural rather than socioeconomic factors predominate, which has important implications for the design and targeting of prevention efforts.

Prognostic models have been developed for patients infected with HIV-1 who start combination antiretroviral therapy (ART) in high-income countries, but not for patients in sub-Saharan Africa. We developed two prognostic models to estimate the probability of death in patients starting ART in sub-Saharan Africa.

Few data exist on the efficacy of the limited regimens for children with HIV, which are available in sub-Saharan Africa.

Background In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life- threatening complication of d4T.Methods GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.Results In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3]<20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (=30 days). SHCO3<15 mmol/l and pH<7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8–1,045.7 and OR 13.9, 95% CI 2.7–86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.Conclusions This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.

Introduction The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings.Methods Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models.Results Analysis included 2,679 individuals followed for a median of 11 months. Median CD4+T-cell count at baseline was 85 cells/µl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyper-lactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART =6 months, weighing =75 kg at baseline.Discussion A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)–infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected children.

BackgroundThe goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence.ObjectiveThis study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions.DesignA mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015–2035) to each epidemiological parameter.ResultsHIV incidence in SA adults (ages 15–49) is expected to decline from 1.4% in 2011–2012 to 0.29% by 2035 (95% CI: 0.10–0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=−0.56), the level of condom use in non-marital relationships (r=−0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=−0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=−0.16).ConclusionsThe virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.