Low-Level Viremia among Adults Living with HIV on Dolutegravir-Based First-Line Antiretroviral Therapy Is a Predictor of Virological Failure in Botswana.

We evaluated subsequent virologic outcomes in individuals experiencing low-level virem ia (LLV) on dolutegravir (DTG)-based first-line antiretroviral therapy (ART) in Botswana. We used a national dataset from 50,742 adults who initiated on DTG-based first-line ART from June 2016-December 2022. Individuals with at least two viral load (VL) measurements post three months on DTG-based first-line ART were evaluated for first and subsequent episodes of LLV (VL:51-999 copies/mL). LLV was sub-categorized as low-LLV (51-200 copies/mL), medium-LLV (201-400 copies/mL) and high-LLV (401-999 copies/mL). The study outcome was virologic failure (VF) (VL ≥ 1000 copies/mL): virologic non-suppression defined as single-VF and confirmed-VF defined as two-consecutive VF measurements after an initial VL < 1000 copies/mL. Cox regression analysis identified predictive factors of subsequent VF. The prevalence of LLV was only statistically different at timepoints >6-12 (2.8%) and >12-24 (3.9%) (p-value < 0.01). LLV was strongly associated with both virologic non-suppression (adjusted hazards ratio [aHR] = 2.6; 95% CI: 2.2-3.3, p-value ≤ 0.001) and confirmed VF (aHR = 2.5; 95% CI: 2.4-2.7, p-value ≤ 0.001) compared to initially virally suppressed PLWH. High-LLV (HR = 3.3; 95% CI: 2.9-3.6) and persistent-LLV (HR = 6.6; 95% CI: 4.9-8.9) were associated with an increased hazard for virologic non-suppression than low-LLV and a single-LLV episode, respectively. In a national cohort of PLWH on DTG-based first-line ART, LLV > 400 copies/mL and persistent-LLV had a stronger association with VF. Frequent VL testing and adherence support are warranted for individuals with VL > 50 copies/mL.

Progress towards the UNAIDS 95-95-95 targets in the Fifth Botswana AIDS Impact Survey (BAIS V 2021): a nationally representative survey.

BACKGROUND: In 2014, UNAIDS set a goal to end the AIDS epidemic by achieving targets for the percentage of people living with HIV who were aware of their status, on antiretroviral therapy (ART), and virally suppressed. In 2020, these targets were revised to 95% for each measure (known as 95-95-95), to be reached among people living with HIV by 2025. We used data from the Fifth Botswana AIDS Impact Survey (BAIS V) to measure progress towards these testing and treatment targets in Botswana. METHODS: BAIS V used a two-stage cluster design to obtain a nationally representative sample of people aged 15-64 years in Botswana. During March-August, 2021, 14 763 consenting participants were interviewed and tested for HIV in their households by survey teams. HIV-positive specimens were tested for viral load, presence of antiretroviral drugs, and recency of infection using the HIV-1 limiting antigen avidity enzyme immunoassay. Estimates of HIV-positive status and use of ART were based on self-report and the analysis of blood specimens for antiretroviral drugs. Viral load suppression was defined as an HIV RNA concentration of less than 1000 copies per mL. HIV incidence was calculated using the recent infection testing algorithm. Data were weighted to account for the complex survey design. FINDINGS: The national HIV prevalence in Botswana among people aged 15-64 years was 20·8% and the annual incidence of HIV infection was 0·2%. 95·1% (men 93·0%, women 96·4%) of people living with HIV aged 15-64 years were aware of their status, 98·0% (men 97·2%, women 98·4%) of those aware were on ART, and 97·9% (men 96·6%, women 98·6%) of those on ART had viral load suppression. Among young people (aged 15-24 years) living with HIV, 84·5% were aware of their status, 98·5% of those aware were on ART, and 91·6% of those on ART had viral load suppression. The prevalance of viral load suppression among all people living with HIV was 91·8%, and varied by district-ranging from 85·3% in Gaborone to 100·0% in Selibe Phikwe. INTERPRETATION: BAIS V is the first population-based survey worldwide to report the achievement of the UNAIDS 95-95-95 goals, both overall and among women. Strategies to reach undiagnosed men and young people, including young women, are needed. FUNDING: US President's Emergency Plan for AIDS Relief.

Malaria control in Botswana, 2008-2012: the path towards elimination.

BACKGROUND: Botswana has made substantial progress towards malaria elimination across the country. This work assessed interventions and epidemiological characteristics of malaria in Botswana, during a period of decreasing transmission intensity. METHODS: National passive malaria surveillance data for five years (2008-2012) were analysed. A district-level, random effects model with Poisson regression was used to explore the association between malaria cases and coverage with long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS). Malaria cases were mapped to visualize spatio-temporal variation in malaria for each year. RESULTS: Within five years, a reduction in malaria prevalence (approximately 98%) and number of deaths (12 to three) was observed. Between 2008 and 2012, 237,050 LLINs were distributed and 596,979 rooms were sprayed with insecticides. Coverage with LLINs and IRS was not uniformly distributed over the study period and only targeted the northern districts with a high malaria burden. The coverage of IRS was associated with a reduction in malaria cases. CONCLUSIONS: Botswana has made significant strides towards its goal of country-wide elimination of malaria. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring countries. In order to accurately monitor progress towards the elimination goal, the malaria control programme (NMP) should strengthen the reporting and capturing of data at household and individual level. Systematic, periodic operational research to feedback the NMP will help to guide and achieve elimination.

Comparison on treatment outcomes of patients enrolled on anti-retroviral therapy at different levels of the health-care system in a high HIV/AIDS setting.

HIV/AIDS prevalence in Botswana is amongst the highest in the world and remains a significant public health problem. however, the introduction of anti-retroviral therapy (ART) lead to a significant reduction in morbidity and mortality. Decentralization of anti-retroviral therapy has improved access to treatment for people living with HIV. Treatment outcomes for patient initiated on treatment at different levels of care is unknown and this study seeks to compare treatment outcomes of patients enrolled on ART at different levels of the health care. This is a retrospective cross-sectional study that included review of data from January 2017 to December 2018. The study was conducted in 2 health districts in the country. Nine hundred and sixty (960) patient's record were included in analysis. More than half (63%) of patients were enrolled at primary care level while 37% were at tertiary level. Sixty one percent (n = 587) were female while 39% (n = 373) were males. There were no statistically significant differences in viral load suppression after 12 months of treatment between patients enrolled at tertiary level and primary care level, x2 = 0.75, p value = 0.56. Time to initiation was longer at tertiary (median = 126) compared to primary are level (median = 18), p < 0.001. We reccommend further decentralization of ART services to lower levels of the health care system to initiate PLWHIV early on treatment and improve their health outcomes and reduce transmission through treatment by prevention.

High-risk behaviors and factors for HIV and sexually transmitted infections among transgender people in Gaborone, Botswana: results from a national survey.

Introduction: key populations and transgender people in particular are at a high risk of HIV infection. However, very little is known about risk behaviors of transgender people in Botswana. The aim of this study was to determine the prevalence of high-risk behaviors for HIV and sexually transmitted infections (STIs) among transgender people in Botswana. Methods: data from the Botswana 2017 Biological and Behavioral Surveillance Survey of HIV/STIs among select key populations (BBSS-2) was used. The cross sectional survey documented behavioral risk factors for these infections. This paper only focused on the analysis of the transgender data. Descriptive analysis was done with IBM Statistical Software for the Social Sciences (SPSS) version 24. Results: there were 56 transgender people identified of which 12 (21.4%) were transgender women. The median age was 24 (interquartile range (IQR) 22-28). Among transgender women, 2 (16.7%) reported concurrent sexual partners and 9 (75%) reported condom use at last intercourse. However, only 7 (58.3%) reported consistent lubricant use. About 45% of the respondents did not know the HIV status of their last male partner. Only one of the transgender women reported intercourse with at least 1 female in the last month. About a third reported that they had STI symptoms in the past year. Alcohol use was reported in 50% of respondents while 83% had disclosed gender identity and had been accepted by their families. However, 25% reported discrimination by a healthcare worker. Conclusion: the high-risk behaviors were frequent among transgender women. This study underlines the need for sustained efforts to reach this key population.

The barriers and facilitators of HIV-exposed infant testing as perceived by HIV-positive mothers in Botswana: A qualitative study.

BACKGROUND: Despite high rates of HIV testing and enrolment of HIV-positive pregnant women on antiretroviral therapy in Botswana, coverage for HIV-exposed infant (HEI) testing remains suboptimal. Many factors can contribute to suboptimal HEI testing rates, but they have seldom been thoroughly investigated in Botswana. Therefore, the aim of this study was to explore the experiences and perspectives of HIV-positive mothers on the barriers and facilitators of HEI testing to inform interventions to promote HEI testing in Botswana. METHODS: We conducted focus group discussions (FGDs) with HIV-positive mothers who gave birth in 2016 at the three largest public hospitals in Botswana. FGDs were held in Maun, Francistown, and Gaborone from September 2019 to March 2020. The maximum variation sampling method was used to select the participants using information that was abstracted from birth registers and other medical records at the study sites. Mothers were asked to describe their HEI testing experiences, what made it easy or difficult for them to return the HEI for testing, and what needs to be done to improve HEI testing in Botswana. A thematic approach was used to analyse the data. RESULTS: Fifteen FGDs with 142 mothers (aged 21-52 years) were held. Participants identified several facilitators to HEI testing, including a mother with adequate knowledge of PMTCT, intensive tracking of HEI by healthcare workers (HCWs), positive attitudes of HCWs toward clients, and social support from significant others. Staff shortages at health care facilities, frequent stock-outs of HIV test kits, fear of stigma, fear of positive test results for the child, and transportation challenges were identified as key barriers to HEI testing. Increasing staffing at healthcare facilities, having adequate supplies of HIV test kits, enhanced HEI tracking, easing access to HEI testing services in rural areas, and providing quality PMTCT education were among the proposed interventions to promote HEI testing. CONCLUSION: Optimizing HEI testing in Botswana will require multi-level interventions at the policy, health system, community, interpersonal, and individual levels.

The utility of a modified WHO TB screening tool among children at a Botswana child welfare clinic.

BACKGROUND: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. OBJECTIVE: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a "Well Child" Clinic (CWC). METHODS: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. RESULTS: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). CONCLUSION: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detection and treatment of TB in HIV exposed children in resource limited settings.

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.

There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.

Five years after Treat All implementation: Botswana's HIV response and future directions in the era of COVID-19.

BACKGROUND: As the relentless coronavirus disease-2019 (COVID-19) pandemic continues to spread across Africa, Botswana could face challenges maintaining the pathway towards control of its HIV epidemic. OBJECTIVE: Utilising the Spectrum GOALS module (GOALS-2021), the 5-year outcomes from the implementation of the Treat All strategy were analysed and compared with the original 2016 Investment Case (2016-IC) projections. Future impact of adopting the new Joint United Nations Programme on HIV/AIDS (UNAIDS) Global AIDS Strategy (2021-2026) targets and macroeconomic analysis estimating how the financial constraints from the COVID-19 pandemic could impact the available resources for Botswana's National HIV Response through 2030 were also considered. METHOD: Programmatic costs, population demographics, prevention and treatment outputs were determined. Previous 2016-IC data were uploaded for comparison, and inputs for the GOALS, AIM, DemProj, Resource Needs and Family Planning modules were derived from published reports, strategic plans, programmatic data and expert opinion. The economic projections were recalibrated with consideration of the impact of the COVID-19 pandemic. RESULTS: Decreases in HIV infections, incidence and mortality rates were achieved. Increases in laboratory costs were offset by estimated decreases in the population of people living with HIV (PLWH). Moving forward, young women and others at high risk must be targeted in HIV prevention efforts, as Botswana transitions from a generalised to a more concentrated epidemic. CONCLUSION: The Treat All strategy contributed positively to decreases in new HIV infections, mortality and costs. If significant improvements in differentiated service delivery, increases in human resources and HIV prevention can be realised, Botswana could become one of the first countries with a previously high-burdened generalised HIV epidemic to gain epidemic control, despite the demands of the COVID-19 pandemic.

Feasibility of oral HIV self-testing in female sex workers in Gaborone, Botswana.

BACKGROUND: Oral HIV self-testing (HIVST) may be useful for increasing testing in persons at elevated risk of acquiring HIV. METHODS: We conducted a pilot study to evaluate the feasibility (defined by uptake) of HIVST among FSW in Gaborone, Botswana. FSW age 18 years and above were recruited through a non-governmental organization serving FSW. FSW with unknown or negative HIV status at screening performed HIVST in the study clinic following brief training. FSW testing HIV-negative were each given two test kits to take home: one kit to perform unassisted HIVST and another to share with others. Feasibility (use) of HIVST (and sharing of test kits with others) was assessed in these women at a study visit four months later. RESULTS: Two hundred FSW were screened. Their average age was 34 years (range 18-59), and 115 (58%) were HIV-positive. Eighty-five (42%) tested HIV-negative at entry and were eligible to take part in the HIVST pilot study. All 85 (100%) agreed to take home HIVST kits. Sixty-nine (81%) of these 85 participants had a follow-up visit, 56 (81%) of whom reported performing HIVST at a mean of three and half months after the initial visit. All 56 participants who performed HIVST reported negative HIVST results. Fifty (73%) of the 69 participants who took HIVST kits home shared them with others. Of the 50 women sharing HIVST kits, 25 (50%) shared with their non-client partners, 15 with a family member, 8 with friends, and 3 with a client. One participant did not test herself but shared both her test kits. Most participants 53/56 (95%) found oral HIVST very easy to use whilst 3/56 (5%) felt it was fairly easy. CONCLUSION: Oral HIVST is feasible among FSW in Gaborone, Botswana. The majority of FSW used the HIVST kits themselves and also shared extra HIVST kits with other individuals.

Acceptability of oral HIV self-testing among female sex workers in Gaborone, Botswana.

BACKGROUND: HIV prevalence among female sex workers (FSW) in sub-Saharan Africa is much higher than in the general population. HIV self-testing (HIVST) may be useful for increasing testing rates in FSW. METHODS: We conducted semi-structured in-depth interviews among FSW, nurses and lay counsellors providing services to FSWs in Botswana. We aimed to gain understanding of perceived acceptability, anticipated barriers, and preferred approaches to HIVST among FSW. Interviews were audio-recorded, transcribed and translated. Transcripts were reviewed and coded independently by two investigators; high inter-coder agreement was achieved (Kappa = 0.80). RESULTS: We interviewed five care providers whose average age was 40 years (SD = 2,64, range = 37-43); three nurses and two counsellors. Thirty FSW were interviewed, with mean age 34 years (range = 20-52). Most (27; 90%) FSW expressed great interest in using HIVST kits. Facilitators of HIVST were: awareness of own risky sexual behaviours, desire to stay healthy, and perceived autonomy over one's healthcare decisions. Perceived advantages of HIVST included convenience, privacy, and perception of decreased stigma. Identified barriers to HIVST included lack of knowledge about the HIVST kit, fear of testing due to anticipated stigma, mistrust of the test's accuracy, doubt of self-competency to perform HIVST, and concerns about not linking to care. Assisting someone to test was noted as good for providing emotional support, but there were concerns about confidentiality breaches. Providers expressed concerns over low literacy among FSWs which could affect comprehension of testing instructions, and competency to perform testing and interpret results. Participants' recommendations for implementation of HIVST included: ensuring wide dissemination of information on HIVST, engaging peers in information-sharing and education, making test kits accessible in FSW-friendly centres, and having clear instructions for linkage to healthcare and support. CONCLUSION: HIVST shows high acceptability among FSWs in Gaborone Botswana, with providers expressing some concerns. Implementation should be peer-driven with healthcare provider oversight.

Five years after treat all implementation: Botswana's HIV response and future directions in the era of COVID-19

Background: As the relentless coronavirus disease-2019 (COVID-19) pandemic continues to spread across Africa, Botswana could face challenges maintaining the pathway towards control of its HIV epidemic.Objective: Utilising the Spectrum GOALS module (GOALS-2021), the 5-year outcomes from the implementation of the Treat All strategy were analysed and compared with the original 2016 Investment Case (2016-IC) projections. Future impact of adopting the new Joint United Nations Programme on HIV/AIDS (UNAIDS) Global AIDS Strategy (2021­2026) targets and macroeconomic analysis estimating how the financial constraints from the COVID-19 pandemic could impact the available resources for Botswana's National HIV Response through 2030 were also considered.Method: Programmatic costs, population demographics, prevention and treatment outputs were determined. Previous 2016-IC data were uploaded for comparison, and inputs for the GOALS, AIM, DemProj, Resource Needs and Family Planning modules were derived from published reports, strategic plans, programmatic data and expert opinion. The economic projections were recalibrated with consideration of the impact of the COVID-19 pandemic.Results: Decreases in HIV infections, incidence and mortality rates were achieved. Increases in laboratory costs were offset by estimated decreases in the population of people living with HIV (PLWH). Moving forward, young women and others at high risk must be targeted in HIV prevention efforts, as Botswana transitions from a generalised to a more concentrated epidemic.Conclusion: The Treat All strategy contributed positively to decreases in new HIV infections, mortality and costs. If significant improvements in differentiated service delivery, increases in human resources and HIV prevention can be realised, Botswana could become one of the first countries with a previously high-burdened generalised HIV epidemic to gain epidemic control, despite the demands of the COVID-19 pandemic.