BACKGROUND Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, −1.3 percentage points; repeated confidence interval, −2.1 to −0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538.)

Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15-49 years and a tuberculosis prevalence of 0•7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. MethodsIn this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. FindingsAmong the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23•3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37•4%) of 163 350, diabetes in 43 885 (27•4%) of 159 932, and HIV in 13 793 (9•1%) of 151 779. Tuberculosis was reported in 5282 (3•6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1•34, 95% CI 1•27-1•43), past tuberculosis (1•26, 1•15-1•38), current tuberculosis (1•42, 1•22-1•64), and both past and current tuberculosis (1•48, 1•32-1•67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1•45, 95% CI 1•22-1•72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29•2% compared with 30•8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with...

Background The first wave of COVID-19 in South Africa peaked in July, 2020, and a larger second wave peaked in January, 2021, in which the SARS-CoV-2 501Y.V2 (Beta) lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves.Methods In this prospective cohort study, we analysed data from the DATCOV national active surveillance system for COVID-19 admissions to hospital from March 5, 2020, to March 27, 2021. The system contained data from all hospitals in South Africa that have admitted a patient with COVID-19. We used incidence risk for admission to hospital and determined cutoff dates to define five wave periods: pre-wave 1, wave 1, post-wave 1, wave 2, and post-wave 2. We compared the characteristics of patients with COVID-19 who were admitted to hospital in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using random-effect multivariable logistic regression.Findings Peak rates of COVID-19 cases, admissions, and in-hospital deaths in the second wave exceeded rates in the first wave: COVID-19 cases, 240•4 cases per 100 000 people vs 136•0 cases per 100 000 people; admissions, 27•9 admissions per 100 000 people vs 16•1 admissions per 100 000 people; deaths, 8•3 deaths per 100 000 people vs 3•6 deaths per 100 000 people. The weekly average growth rate in hospital admissions was 20% in wave 1 and 43% in wave 2 (ratio of growth rate in wave 2 compared with wave 1 was 1•19, 95% CI 1•18-1•20). Compared with the first wave, individuals admitted to hospital in the second wave were more likely to be age 40-64 years (adjusted odds ratio [aOR] 1•22, 95% CI 1•14-1•31), and older than 65 years (aOR 1•38, 1•25-1•52), compared with younger than 40 years; of Mixed race (aOR 1•21, 1•06-1•38) compared with White race; and admitted in the public sector (aOR 1•65, 1•41-1•92); and less likely to be Black (aOR 0•53, 0•47-0•60) and Indian (aOR 0•77, 0•66-0•91), compared with White; and have a comorbid condition (aOR 0•60, 0•55-0•67).For multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 31% increased risk of in-hospital mortality in the second wave (aOR 1•31, 95% CI 1•28-1•35). In-hospital case-fatality risk increased from 17•7% in weeks of low admission (<3500 admissions) to 26•9% in weeks of very high admission (>8000 admissions; aOR 1•24, 1•17-1•32).Interpretation In South Africa, the second wave was associated with higher incidence of COVID-19, more rapid increase in admissions to hospital, and increased in-hospital mortality. Although some of the increased mortality can be explained by admissions in the second wave being more likely in older individuals, in the public sector, and by the increased health system pressure, a residual increase in mortality of patients admitted to hospital could be related to the new Beta lineage.

Objectives To determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART). Design A prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa. Methods Among 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared. Results Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7–115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14–7.29) after adjusting for baseline factors. Conclusion Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.

Background Few studies have assessed metabolic and body composition alterations in young perinatally HIV-infected African children on antiretroviral therapy (ART). We compared metabolic profiles and regional fat of children on a combination of ritonavir-boosted lopinavir (lopinavir/ritonavir), lamivudine, and stavudine to those switched to nevirapine, lamivudine, and stavudine. Methods This study evaluated metabolic and body composition outcomes in 156 HIV-infected children completing a randomized trial that assessed the continued use of lopinavir/ritonavir-based or switch to NVP-based ART in Johannesburg, South Africa (2005–2010). Fasting total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were measured. Total and regional body fat (BF) were estimated by anthropometry and bioelectrical impedance analysis (BIA). A clinical assessment for lipodystrophy was conducted. Modified intent-to-treat analyses were conducted. Results 156 children (mean age 5.1±0.8 years, mean duration of treatment 4.2±0.7 years, mean time since randomization 3.4±0.7 years) were enrolled. 85 were randomized to the lopinavir/ritonavir- and 71 to the nevirapine-group. The lopinavir/ritonavir-group had lower mean HDL (1.3±0.4 vs. 1.5±0.4 mmol/L, p<0.001) and higher mean TC (4.4±1.0 vs. 4.1±0.8 mmol/L, p=0.097), LDL (2.6±0.9 vs. 2.3±0.7mmol/L, p=0.018), and triglycerides (1.1±0.4 vs. 0.8±0.3 mmol/L, p<0.001). The lopinavir/ritonavir-group had more total BF by mean skinfold sum (43±11.1 vs. 39±10.1 mm, p=0.031) and BF% by BIA (17.0±7.0 vs. 14.1±8.0%, p=0.022). Thirteen (8.4%) met criteria for lipodystrophy. Conclusions Unfavorable alterations in lipid profile and triglycerides, and differences in fat are detectable in young HIV-infected South African children receiving lopinavir/ritonavir-based vs. those switched to nevirapine-based regimens. Interventions to mitigate these alterations are warranted to reduce long-term cardiovascular disease risk.

BACKGROUND-Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

BACKGROUND-Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

Background Both HIV infection and antiretroviral therapy are associated with dyslipidemias in adults but there are fewer data on outcomes in young children. Here we examined lipid profile changes in a cohort of young children before and after suppression on an initial ritonavir-boosted lopinavir (LPV/r)-based regimen and after switch to a nevirapine (NVP)-based regimen. Methods 195 HIV-infected children who initiated LPV/r-based therapy when <24 months of age at one site in Johannesburg, South Africa, and who achieved viral suppression (<400copies/ml sustained for ≥ 3 months) were randomised to either continue on the LPV/r-based regimen (n=99) or to switch to a NVP-based regimen (n=96). Non-fasting concentrations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) were measured pre-treatment, at randomization when suppressed, and at 9, 20 and 31 months post-randomization. Results Median age at treatment initiation was 9 months and the initial regimen was maintained for an average of 9 months before randomization. TC, LDL and HDL increased from pre-treatment to randomization (p<0.0001) and TC/HDL ratio and TG decreased (p<0.0001). After switching to NVP, HDL was significantly higher (p<0.02) and TC/HDL and TG significantly lower (p<0.0001) through 31 months post-switch relative to remaining on the LPV/r-based regimen. Conclusion Initiating antiretroviral therapy was associated with changes to a more favorable lipid profile in young children. Switching from a LPV/r-based regimen to a NVP-based regimen accentuated and continued these improvements. Investigation of safe and effective methods for managing dyslipidemias in children of different ages in resource-limited settings is warranted.