BACKGROUND:HIV testing at birth supports timely infant HIV diagnosis and treatment. We evaluated the operational feasibility and effectiveness of facility-based, risk-stratified birth testing for newborns at high risk and moderate risk of vertical HIV transmission in Botswana. METHODS:We tested newborns at high risk or moderate risk of HIV acquisition at 35 delivery facilities selected based on delivery volume. At-risk newborns were identified by maternal delivery record review and tested after mothers provided verbal consent during brief interviews. Included infants were born to mothers 18 years and older, weighing 1·5 kg and over, and had one or more maternal risk factors; infants unlikely to survive 24 months were excluded. High-risk was defined as documented maternal HIV-1 viral load of 40 copies per mL or above during pregnancy, maternal CD4 count under 350 cells per μL during pregnancy, fewer than 12 weeks of maternal antiretroviral therapy (ART) use before delivery, or self-reported poor maternal adherence to ART (ie, more than three missed doses during pregnancy). Moderate risk included a new HIV diagnosis in pregnancy or other clinical concerns. Dried blood spots were evaluated using GeneXpert, with positive results confirmed by COBAS TaqMan. Children testing negative were retested at 6 weeks, per national guidelines. FINDINGS:From July 4, 2022, to July 4, 2024, 8844 total newborns were delivered to women living with HIV. Of these, 2737 newborns with any risk factor of concern to government midwives were identified, testing was offered to their mothers, and 96% accepted, yielding a total of 2627 newborns (30%) exposed to HIV who were tested at birth. HIV testing occurred at a median of 22 h of life (IQR 13-41). 1234 (14·0%) infants were high-risk and 1393 (15·8%) were moderate-risk by study-specific criteria; 1283 infants (48·8%) were female and 1344 (51·2%) were male; demographic data on race and ethnicity were not collected, although all participants were Black Africans. HIV was confirmed in 14 (0·5%) of 2627 newborns (13 classified as high-risk), with infant treatment-dose nevirapine-lamivudine-zidovudine started at a median of 2·7 days (IQR 2·0-3·3). Post-exposure prophylaxis for the 2613 newborns with negative birth testing results was zidovudine in 1037 (39·5%), nevirapine-lamivudine-zidovudine in 1497 (57·0%), and no prophylaxis documented in 79 (3·0%). 6-week follow-up testing was documented for 2211 infants (84·6%) with negative birth testing, with only three new infections (0·1%; one at high risk, two at moderate risk; and all were prescribed three-drug prophylaxis). INTERPRETATION:Near-point-of-care HIV testing at birth for high-risk newborns can identify the majority of HIV transmissions in early life. Simplified post-exposure prophylaxis may be appropriate in the setting of available maternal ART, even among infants at high risk. FUNDING:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health. TRANSLATION:For the Setswana translation of the abstract see Supplementary Materials section.
BACKGROUND:Dolutegravir resistance is increasingly reported in treatment-experienced people with HIV in low-income and middle-income countries. Resistance testing resources are sparse, and viral rebound often reflects adherence lapses rather than resistance. Efficient strategies are needed to target testing to individuals at highest risk. We evaluated a reflex laboratory approach using plasma dolutegravir exposure to guide resistance testing in routine care. METHODS:In this prospective implementation study at two public-sector clinics in Johannesburg, South Africa, we analysed adults (aged ≥18 years) on dolutegravir-based antiretroviral therapy (ART) with viral rebound of 400 copies per mL or higher. From May 18, 2023, to Jan 10, 2025, we tested residual routine viral load samples for dolutegravir exposure using an enzyme immunoassay. If dolutegravir was detectable (≥20 ng/mL), we did reflex resistance testing on the same specimen; retrospective sequencing was done at study end for dolutegravir-undetectable samples. We modelled costs comparing the reflex approach with standard of care. FINDINGS:We analysed 400 samples from 288 individuals; 160 (56%) were female and 128 (44%) male, the median age was 44 years (IQR 35-50), and 240 (83%) had previous non-dolutegravir ART exposure. Plasma dolutegravir was detectable in 108 (38%) participants. Among those with successful sequencing, dolutegravir resistance occurred in 13 (13%) of 102 participants with detectable dolutegravir and three (2%) of 138 with undetectable dolutegravir, yielding an overall prevalence of 6·7% dolutegravir resistance and a negative predictive value for absence of dolutegravir resistance of 97·8% (95% CI 93·5-99·5). Dolutegravir resistance was associated with detectable dolutegravir (odds ratio [OR] 3 [95% CI 1-9], p=0·031), nucleoside reverse transcriptase inhibitor mutations (OR 33 [4-264], p=0·0009), non-nucleoside reverse transcriptase inhibitor mutations (OR 17 [2-135], p=0·0068), or M184V (OR 20 [4-92], p=0·0002). Cost modelling showed a 23% reduction in monitoring cost per person using the reflex strategy after confirmed viraemia versus current national guidelines. INTERPRETATION:Laboratory-initiated reflex plasma dolutegravir exposure testing provides an objective, cost-efficient strategy to predict the absence of dolutegravir resistance and supports adherence management, enabling timely, individualised treatment decisions. Reflex dolutegravir exposure testing could enhance clinical decision making, improve treatment outcomes, and strengthen HIV treatment and resistance monitoring algorithms in programmatic settings. FUNDING:The Amsterdam Dinner Foundation and Aidsfonds, the Netherlands Organisation for Scientific Research, ZonMw, and WOTRO.
