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.

BackgroundRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.Methods and FindingsWe reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.ConclusionsMost TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance...

Background Antiretroviral treatment (ART) initiatives have now been established in many sub-Saharan African countries showing early benefits. To date, few results are available concerning long-term clinical outcomes in these treatment programs. Methods Response to ART is described in the first HIV–1C infected adults enrolled in the Botswana ART program in 2002. Data analysis was conducted on available longitudinal data up to April 1st, 2007. Results 633 severely immunodeficient patients with a median CD4+ cell count of 67 cells/mm3 were initiated on NNRTI-based combination ART and followed for a median of 41.9 months. The median CD4+ increases were 169 cells/mm3, 302 cells/mm3, and 337 cells/mm3 at 1, 3, and 5 years, respectively. The percentages of patients with a viral load of less than 400 copies/mL at 1, 3, and 5 years were 91.3%, 90.1%, and 98.3%, respectively. 75% of patients did not miss a single, or missed only one, monthly ART pick-up per year with a mean pick-up rate of 92.5%. The Kaplan-Meier survival estimates (95% CI) at 1, 3, and 5 years were 82.7% (81.2%, 84.3%), 79.3% (77.6%, 81.0%), and 79.0% (77.3%, 80.7%), respectively. At six months, the risk of treatment modification for anemia was 6.94% (5.9%, 8.0%) for cutaneous hypersensitivity reactions, 1.3% (0.8%, 1.7%), and 1.1% (0.7%, 1.6%) for hepatotoxicity. Conclusions This initial group of adults on ART in Botswana had excellent sustained immunologic, virologic, and clinical outcomes for up to five years of follow-up with low mortality among those surviving into the second year of antiretroviral treatment.

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As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV=AIDS, substance and=or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient selfreport, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates ( p value <0.02). A significant proportion (81.3%) of cART-treated adults were adherent to their prescribed treatment, with rates superior to those reported in resource-rich settings. Adherence rates were poorest among those just starting cART, most likely due to the presence of ARV-related toxicity. Adherence was lower among those who have been treated for longer periods of time (greater than 1 year), suggesting complacency,

An excellent response to HAART was observed among HIV-1C-infected patients, paralleling those seen elsewhere. Despite excellent responses, high rates of toxicity were observed for ddI + d4T-containing regimens.