BACKGROUND-A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies.METHODS-We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS-FromAugust 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele,

Summary Background Global HIV programs continue to experience challenges achieving the high rates of HIV testing and treatment needed to optimize health and reduce transmission. Botswana represents a useful “demonstration case” in assessing the feasibility of achieving the new UNAIDS targets for 2020: 90% of all persons living with HIV knowing their status, 90% of these individuals receiving sustained antiretroviral treatment (ART), and 90% of those on ART having virologic suppression (“90–90–90”). Methods A population-based random sample of individuals was recruited and interviewed in 30 rural and peri-urban communities from October 2013 to November 2015 in Botswana as part of a large, ongoing PEPFAR-funded community-randomized trial designed to evaluate the impact of a combination prevention package on HIV incidence. A random sample of approximately 20% of households in each of these 30 communities was selected. Consenting household residents aged 16–64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in absence of documentation of positive HIV status. HIV-1 RNA testing was performed in all HIV-infected participants, regardless of treatment status. Findings Eighty-one percent of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12,610 participants surveyed, 3,596 (29%) were HIV infected; 2,995 (83·3%) of these individuals already knew their HIV status. Among those who knew their HIV status, 2,617 (87·4%) were currently receiving ART (this represented 95% of those eligible for ART by current Botswana national guidelines, and 73% of all HIV-infected persons). We obtained an HIV-1 RNA result in 99·7% of HIV-infected participants. Of the 2,609 individuals currently receiving ART with a viral load measurement, 2,517 (96·5%) had HIV-1 RNA ≤400 copies/mL. Overall, 70·2% of HIV-infected persons had virologic suppression, close to the UNAIDS target of 73%. Results of three sensitivity analyses to account for possible uncertainty due to non-participation and under-representation of urban areas, revealed somewhat lower, but nevertheless remarkably high 90–90–90 coverage. Interpretation Botswana, a resource-constrained setting with high HIV prevalence, appears to have achieved very high rates of HIV testing, treatment coverage, and virologic suppression for those on ART in this population-based survey, despite the Botswana ART initiation threshold of ≤350 cells/mm3. These findings provide evidence that the UNAIDS 90-90-90 targets, while ambitious, are achievable even in resource-constrained settings with high HIV burden. Funding The United States President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC).

BACKGROUND-The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.METHODS-We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios.

IMPORTANCE Maternal antiretroviral treatment (ART) started before conception may increase the risk for adverse birth outcomes among women with human immunodeficiency virus (HIV) infection, but whether the risk differs by ART regimen is unknown.OBJECTIVE To compare the risk for selected birth outcomes by maternal ART regimen. DESIGN, SETTING, AND PARTICIPANTSThis observational birth outcomes surveillance study compared all live births and stillbirths with a gestational age of at least 24 weeks in 8 geographically dispersed government hospitals throughout Botswana (approximately 45% of births nationwide). Data were collected from August 15, 2014, through August 15, 2016.EXPOSURES Births among HIV-infected women who started 3-drug ART regimens before their last menstrual period and did not switch or stop ART in pregnancy were considered to be ART exposed from conception. MAIN OUTCOMES AND MEASURESThe primary outcomes were any adverse birth outcome, including stillbirth, preterm birth (<37 weeks), small size for gestational age (SGA; <10th percentile of weight for gestational age) or neonatal death (<28 days from delivery), and any severe adverse outcome, including very preterm birth (<32 weeks), very SGA (<3rd percentile of weight for gestational age), stillbirth, and neonatal death. RESULTS Information was available for 47 027 of 47 124 births (99.8%) at surveillance maternity hospitals (mean [SD] age of mothers, 26.86 [6.45] years). Among 11 932 HIV-exposed infants, 5780 (48.4%) were ART exposed from conception. Adverse birth outcomes were more common among HIV-exposed infants than HIV-unexposed infants (39.6% vs 28.9%; adjusted relative risk [ARR], 1.40; 95% CI, 1.36-1.44). The risk for any adverse birth outcome was lower among infants exposed from conception to tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TDF-FTC-EFV) (901 of 2472 [36.4%]) compared with TDF-FTC and nevirapine (NVP) (317 of 760 [41.7%];

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.