INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m(2) (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m(2), and CD4 counts <200 cells/μL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/μL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

HIV linkage, and retention are key weaknesses in South Africa's national antiretroviral therapy (ART) program, with the greatest loss of patients in the HIV treatment pathway occurring before ART initiation. This study investigated linkage-to and early-retention-in-care (LTRIC) rates among adults newly diagnosed with HIV in a high-HIV prevalent rural district. We conducted an observational prospective cohort study to investigate LTRIC rates for adults with a new HIV diagnosis in South Africa. Patient-level survey and clinical data were collected using a one-stage-cluster design from 18 healthcare facilities and triangulated between HIV and laboratory databases and registered deaths from Department of Home Affairs. We used Chi-square tests to assess associations between categorical variables, and results were stratified by HIV status, sex, and age. Of the 5,637 participants recruited, 21.2% had confirmed HIV, of which 70.9% were women, and 46.5% were aged 25-34 years. Although 82.7% of participants were linked-to-care within 3 months, only 46.1% remained-in-care 12 months after initiating ART and 5.2% were deceased. While a significantly higher proportion of men were linked-to-care at 3 months compared to women, a significant proportion of women (49.5%) remained-in-care at 12 months than men (38.0%). Post-secondary education and child support grants were significantly associated with retention. We found high linkage-to-care rates, but less than 50% of participants remained-in-care at 12 months. Significant effort is required to retain people living with HIV in care, especially during the first year after ART initiation. Our findings suggest that interventions could target men to encourage HIV testing.

As COVID-19 cases increased during the first weeks of the pandemic in South Africa, the National Institute of Communicable Diseases requested assistance with epidemiologic and surveillance expertise from the US Centers for Disease Control and Prevention South Africa. By leveraging its existing relationship with the National Institute of Communicable Diseases for >2 months, the US Centers for Disease Control and Prevention South Africa supported data capture and file organization, data quality reviews, data analytics, laboratory strengthening, and the development and review of COVID-19 guidance This case study provides an account of the resources and the technical, logistical, and organizational capacity leveraged to support a rapid response to the COVID-19 pandemic in South Africa.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Exposure of infants to antiretroviral drugs for prevention of mother-to-child transmission can induce resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Data from nine national surveys of pretreatment drug resistance in children newly diagnosed with HIV show high levels of resistance to NRTIs included in first-line antiretroviral treatment (ART) regimens (dual abacavir-lamivudine/emtricitabine resistance). Additional research is needed to determine the impact of NRTI resistance on treatment response and optimize infant ART.

INTRODUCTION: HIV testing at birth of HIV-exposed infants (HEIs) may improve the identification of infants infected with HIV in utero and accelerate antiretroviral treatment (ART) initiation. METHODS: ICAP at Columbia University supported implementation of a national pilot of HIV testing at birth (0-7 days) in Eswatini at 2 maternity facilities. Dried blood spot (DBS) samples from neonates of women living with HIV (WLHIV) were collected and processed at the National Molecular Reference Laboratory using polymerase chain reaction (PCR). Mothers received birth test results at community health clinics. We report data on HIV birth testing uptake and outcomes for HIV-positive infants from the initial intensive phase (October 2017-March 2018) and routine support phase (April-December 2018). RESULTS: During the initial intensive pilot phase, 1669 WLHIV delivered 1697 live-born HEI at 2 health facilities and 1480 (90.3%) HEI received birth testing. During the routine support phase, 2546 WLHIV delivered and 2277 (93.5%) HEI received birth testing. Overall October 2017-December 2018, 22 (0.6%) infants of 3757 receiving birth testing had a positive PCR test, 15 (68.2%) of whom were successfully traced and linked for confirmatory testing (2 infants were reported by caregivers to have negative follow-up HIV tests). Median time from birth test to receipt of results by the caregiver was 13 days (range: 8-23). Twelve (60.0%) of 20 infants confirmed to be HIV-positive started ART at median age of 17.5 days (12-43). One mother of an HIV-positive infant who was successfully traced refused ART following linkage to care and another child died after ART initiation. Three infants (15.0%) had died by the time their mothers were reached and 4 (15.0%) infants were never located. CONCLUSION: This pilot of universal birth testing in Eswatini demonstrates the feasibility of using a standard of care approach in a low resource and high burden setting. We document high uptake of testing for newborns among HIV-positive mothers and very few infants were found to be infected through birth testing.

Background: Prevention of mother-to-child transmission (PMTCT) of HIV programs have been scaled-up in many low- and middle-income countries; however, HIV drug resistance (HIVDR) data amongst HIV-1-infected young children remain limited. Methods: Surveys of pre-treatment HIVDR amongst children younger than 18 months of age who were diagnosed with HIV through Early Infant Diagnosis were conducted in five sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization guidance. De-identified demographic and clinical data were used to explore risk factors associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. Results: Among the 1,450 genotypes analyzed, 1,048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1 % showed resistance to one or more antiretroviral drug, with 53.0% and 8.8% having resistance to one or more NNRTI or nucleoside reverse transcriptase inhibitor, respectively. NNRTI resistance was particularly high in children exposed to antiretroviral drugs through PMTCT; adjusted odds ratios 1.8 (95% confidence interval (CI): 1.3 - 2.6) for maternal exposure only and 2.4 (CI: 1.6 - 3.6) for neonatal exposure only. Conclusions: Protease inhibitor-based regimens in children younger than three years are currently recommended by WHO but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scale-up of pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

BACKGROUND: Antiretroviral (ARV) prophylaxis effectively reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV). However, it is unclear whether stopping ARVs after breastfeeding cessation affects maternal HIV disease progression. We assessed 18-24-month postpartum disease progression risk among women in a randomized trial assessing efficacy and safety of prophylactic maternal ARVs. METHODS: From 2005 to 2008, HIV-infected pregnant women with CD4+ counts of 200-500/mm(3) were randomized to receive either triple ARV (zidovudine, lamivudine, and lopinavir/ritonavir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose nevirapine without postpartum prophylaxis). Maternal disease progression was defined as the combined endpoint of death, World Health Organization clinical stage 4 disease, or CD4+ counts of <200/mm(3). RESULTS: Among 824 randomized women, 789 had at least 1 study visit after cessation of ARV prophylaxis. Following delivery, progression risk up to 24 months postpartum in the triple ARV arm was significantly lower than in the AZT/sdNVP arm (15.7 vs 28.3; P =. 001), but the risks of progression after cessation of ARV prophylaxis (rather than after delivery) were not different (15.0 vs 13.8 18 months after ARV cessation). Among women with CD4+ counts of 200-349/mm(3) at enrollment, 24.0 (95 confidence interval [CI], 15.7-35.5) progressed with triple ARV, and 23.0 (95 CI, 17.8-29.5) progressed with AZT/sdNVP, whereas few women in either arm (<5) with initial CD4+ counts of >=350/mm(3) progressed. CONCLUSIONS: Interrupting prolonged triple ARV prophylaxis had no effect on HIV progression following cessation (compared with AZT/sdNVP). However, women on triple ARV prophylaxis had lower progression risk during the time on triple ARV. Given the high rate of progression among women with CD4+ cells of <350/mm(3), ARVs should not be discontinued in this group. CLINICAL TRIALS REGISTRATION: ISRCTN71468410. (2012 The Author.)