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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.

Objectives To evaluate whether etonogestrel concentrations are reduced to a level that could potentially reduce contraceptive efficacy when the etonogestrel contraceptive implant is used concomitantly with dolutegravir-based antiretroviral therapy (ART). Study design We conducted a non-randomized, open-label, cross-sectional pharmacokinetic study among women using single-rod etonogestrel contraceptive implants in Botswana. We compared plasma etonogestrel concentrations, sampled at a single time-point between 3 and 12 months from implant insertion, among implant users living with HIV and receiving dolutegravir-based ART with HIV-negative implant users. We also assessed concentrations among implant users living with HIV and receiving efavirenz-based ART. We compared geometric mean etonogestrel concentrations analyzing data from 142 participants: 97 HIV-negative, 30 using dolutegravir, and 15 using efavirenz. Results The groups were similar. Duration of implant use was between 3 and 12 months (median = 5). Geometric mean etonogestrel plasma concentrations and 90% confidence intervals of the mean were 227.5(212.4–243.8), 289.6(251.8–333.0) and 76.4(63.9–91.4) pg/mL among the HIV-negative, dolutegravir- and efavirenz-based ART groups, respectively. All women in the HIV-negative and dolutegravir-based ART groups had etonogestrel concentrations above 90 pg/mL; 9/15 women (60%) using efavirenz-based ART had concentrations below 90 pg/mL. On average, etonogestrel levels were lower among individuals who had implants inserted for longer durations. Conclusions Implant users receiving dolutegravir-based ART had a higher mean etonogestrel concentration compared to HIV-negative women, and none had etonogestrel concentrations below the posited threshold for ovulation suppression. In contrast, women in the efavirenz-group had much lower etonogestrel concentrations. Overall, these data provide evidence that the etonogestrel implant may be effectively combined with dolutegravir-based ART regimens. Implications The etonogestrel implant remains a highly effective contraceptive option for women living with HIV who use dolutegravir-based ART.

There are limited data on the effectiveness of dolutegravir (DTG)-based combination antiretroviral therapy (ART) in real-life settings in southern Africa where HIV-1 subtype C predominates. We report a patient infected with HIV-1 subtype C on DTG-based ART previously exposed to raltegravir who developed multidrug resistance mutations to four antiretroviral classes. There is need for drug resistance monitoring and clinical vigilance to ensure effectiveness of HIV treatment programs even in the era of DTG-based ART.

BackgroundRoll-out of Integrase Strand Transfer Inhibitors (INSTIs) such as dolutegravir for HIV combination antiretroviral therapy (cART) in sub-Saharan Africa necessitates the development of affordable HIV drug resistance (HIVDR) assays targeting the Integrase gene. We optimised and evaluated an in-house integrase HIV-1 drug resistance assay (IH-Int) and compared it to a commercially available assay, ViroSeq™ Integrase Genotyping kit (VS-Int) amongst HIV-1 clade C infected individuals.MethodsWe used 54 plasma samples from treatment naïve participants and one plasma sample from a patient failing INSTI based cART. Specimens were genotyped using both the VS-Int and IH-Int assays. Stanford HIV drug resistance database were used for integrase resistance interpretation. We compared the major and minor resistance mutations, pairwise nucleotide and amino-acid identity, costs and assay time.ResultsAmong 55 specimens tested with IH-Int, 53 (96.4%) successfully amplified compared to 45/55 (81.8%) for the VS-Int assay. The mean nucleotide and amino acid similarity from 33 paired sequences was 99.8% (SD ± 0.30) and 99.8% (SD ± 0.39) for the IH-Int and VS-Int assay respectively. The reagent cost/sample were 32 USD and 147 USD for IH-Int and VS-Int assay, respectively. All sequenced samples were confirmed as HIV-1 subtype C.ConclusionsThe IH-Int assay had a high amplification success rate and high concordance with the commercial assay. It is significantly cheaper compared to the commercial assay. Our assay has the needed specifications for routine monitoring of participants on Dolutegravir based regimens in Botswana.

Little is published about the disclosure of parents' own HIV status to their children in Africa. Research shows that keeping family secrets from children, including those related to a parent's HIV status, can be detrimental to their psychological well-being and to the structure of the family. Further, children with HIV-positive parents have been shown to be more vulnerable to poorer reproductive health outcomes. This qualitative study in Botswana conducted in-depth interviews among 21 HIV-positive parents on antiretroviral therapy. The data revealed that parents found discussing the issue of HIV with children difficult, including disclosing their own HIV status to them. Reasons for disclosing included: children being HIV positive, the rest of the family knowing, or the parent becoming very sick. Reasons for not disclosing included: believing the child to be too young, not knowing how to address the issue of HIV, that it would be "too painful" for the child/ren. Concern that other people might find out about their status or fear of children experiencing stigmatising behaviour. Interviews elucidated the difficulty that parents have in discussing their own HIV status and more general sexual health issues with their children. Parents and other guardians require support in managing age-appropriate disclosure to their children. This may further enable access to forums that can help children cope with their fears about the future and develop life skills in preparation for dealing with relationships of a sexual nature and sexual health as children move into adulthood. In developing such support mechanisms, changing family roles in Botswana need to be taken into consideration and the role of other family members in the upbringing of children in Tswana society need to be recognised and utilised.

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 Antiretroviral Treatment Program in 2002. Data analysis was conducted on available longitudinal data up to 1st April 2007. RESULTS: Six hundred thirty-three severely immunodeficient patients with a median CD4+ cell count of 67 cells/microl were initiated on non-nucleoside reverse transcriptase inhibitor-based combination ART and followed for a median of 41.9 months. The median CD4+ cell count increases were 169 302 and 337 cells/microl 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. Seventy-five percent of patients did not miss a single or missed only one monthly ART pickup per year with a mean pickup rate of 92.5%. The Kaplan-Meier survival estimates [95% confidence interval (CI)] at 1 3 and 5 years were 82.7% (81.2 and 84.3%) 79.3% (77.6 and 81.0%) and 79.0% (77.3 and 80.7%) respectively. At 6 months the risk of treatment modification for anemia was 6.94% (5.9 and 8.0%) for cutaneous hypersensitivity reactions 1.3% (0.8 and 1.7%) and 1.1% (0.7 and 1.6%) for hepatotoxicity. CONCLUSION: This initial group of adults on ART in Botswana had excellent sustained immunologic virologic and clinical outcomes for up to 5 years of follow-up with low mortality among those surviving into the second year of ART.

In parallel with the rollout of Botswana’s national antiretroviral therapy (ART) program, the Botswana Ministry of Health established the KITSO AIDS Training Program by entering into long-term partnerships with the Botswana–Harvard AIDS Institute Partnership for HIV Research and Education and others to provide standardized, country-specific training in HIV/AIDS care. The KITSO training model has strengthened human capacity within Botswana’s health sector and been indispensable to successful ART rollout. Through core and advanced training courses and clinical mentoring, different cadres of health care workers have been trained to provide high-quality HIV/AIDS care at all ART sites in the country. Continuous and standardized clinical education will be crucial to sustain the present level of care and successfully address future treatment challenges.

Reports from southern Africa, an area in which human immunodeficiency virus type 1 (HIV-1) infection is caused almost exclusively by subtype C (HIV-1C), have shown increased rates of anemia in HIV-infected populations compared with similar acquired immunodeficiency syndrome (AIDS) patients in the United States, an area predominantly infected with subtype B (HIV-1B). Recent findings by our group demonstrated a direct association between HIV-1 infection and hematopoietic progenitor cell health in Botswana. Therefore, using a single-colony infection assay and quantitative proviral analysis, we examined whether HIV-1C could infect hematopoietic progenitor cells (HPCs) and whether this phenotype was associated with the higher rates of anemia found in southern Africa. The results show that a significant number of HIV-1C, but not HIV-1B, isolates can infect HPCs in vitro (P < .05). In addition, a portion of HIV-1C–positive Africans had infected progenitor cell populations in vivo, which was associated with higher rates of anemia in these patients (P < .05). This represents a difference in cell tropism between 2 geographically separate and distinct HIV-1 subtypes. The association of this hematotropic phenotype with higher rates of anemia should be considered when examining anti-HIV drug treatment regimens in HIV-1C–predominant areas, such as southern Africa.

Clinical observations suggest that HIV-1 infection causes higher anemia rates in patients in southern Africa than in those in the United States. To explore this difference we performed a cross-sectional exploratory study on the effect of HIV-1 infection on hematopoiesis in Botswana by examining hematological presentation, HIV disease state, hematopoietic progenitor cell number, and circulating viral levels in HIV-infected patients and HIV-uninfected controls. We found significant associations between CD34(+) and CD4(+) cell counts in HIV-positive patients. Significant relationships were also seen between the CD34(+) CD4(+) cell population and hemoglobin levels, as well as colony-forming ability. These associations, however, were not seen in uninfected controls. Circulating viral p24 levels were found to correlate significantly with CD34(+) cell count, CD34(+) CD4(+) cell count, and colony-forming ability. These results demonstrate a direct association between HIV-1 infection in southern Africa and hematopoietic progenitor cell health.

In industrialized countries, it is recommended that adults with human immunodeficiency virus type 1 (HIV-1) infection undergo baseline screening for pathogens that might cause latent or active infections, such as syphilis, hepatitis B, hepatitis C, infection due to Toxoplasma gondii, and cytomegalovirus infection. A paucity of data exist from sub-Saharan Africa describing the prevalence of these pathogens. We report data for HIV-1-infected adults referred for initiation of highly active antiretroviral therapy in Botswana.

Among 16 human immunodeficiency virus-infected (subtype C) Batswana patients who failed nelfinavir (NFV)-containing regimens, the most prevalent mutation observed was D30N (54%), followed by L90M (31%). L89I, K20T/I, and E35D polymorphic changes were also identified. These findings suggest that subtype C viruses in Botswana may develop resistance to NFV via subtype-specific pathways.

To describe the response to highly active antiretroviral treatment (HAART) in a public sector pilot antiretroviral (ARV) treatment program in Botswana.The response to HAART is described in adult HIV-infected ARV-naive patients initiating treatment from April 2001 to January 2002 at Princess Marina Hospital in Gaborone, Botswana. Patients had medical and laboratory evaluations before initiating ARV treatment and were followed longitudinally. For analysis, data were collected from charts and patient management records.One hundred fifty-three ARV-naive patients initiated HAART. Most received didanosine plus stavudine (ddI + d4T) with efavirenz or nevirapine. The mean CD4 cell count increase was 149 cells/mm at 24 weeks and 204 cells/mm at 48 weeks. The percentage of patients with an HIV-1 RNA levelor =400 copies/mL was 87.0% at 24 weeks and 78.8% at 48 weeks. The Kaplan-Meier 1-year survival estimate was 84.7% (79.0%, 90.8%), with a 3.2-fold increased risk (P = 0.004) of mortality among patients with a CD4 cell count50 cells/mm. The 1-year Kaplan-Meier estimate of toxicity-related drug switches was 32.2% (20.3%, 40.4%). The most common toxicity was peripheral neuropathy, occurring more frequently in patients with a preexisting diagnosis of peripheral neuropathy and among those placed on ddI + d4T-containing regimens.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.

Countries in sub-Saharan Africa are under significant pressure to open large-scale, public antiretroviral treatment clinics. Many lessons have been learned in Botswana, where the first public antiretroviral treatment clinic in Africa was established. The availability of core, well-trained medical staff will be the primary factor that limits a rapid scale-up of antiretroviral treatment programs.

To detect and characterize polymerase gene ( pol) polymorphisms and mutation patterns in HIV-1C-infected Batswana patients treated with reverse transcriptase inhibitors, samples from AIDS patients treated with highly active antiretroviral therapy (HAART) were sequenced for the region encompassing the entire HIV-1 protease (PR) and the first 335 amino acids of reverse transcriptase (RT). Amongst the 16 patients treated with antiretroviral (ARV) drugs, eight started HAART regimens containing didanosine, stavudine and nevirapine (ddI/d4T/NVP) or efavirenz (EFV) (arm A) while the others started with zidovudine (AZT) and lamivudine (3TC) given together as combivir (CBV) with either NVP or EFV as arm B. Arm B is the first line regimen currently provided by the Botswana ARV national programme. Greater efficacy, in terms of treatment duration, was observed in patients in arm B (14 months) as compared with patients in arm A (9 months); P10 RNA copies/ml) and a significantly improved immunological parameter (ΔCD4=207.0 +48.1 cells/μl; P

Tremendous progress has been made with the scale-up of antiretroviral therapy in Africa, with an estimated seven million people now receiving antiretroviral therapy in the region. The long-term success of antiretroviral therapy programs depends on appropriate strategies to deal with potential threats, one of which is the emergence and spread of antiretroviral drug resistance. Whilst public health surveillance forms the mainstay of the World Health Organization approach to antiretroviral drug resistance, there is likely to be increasing demand for access to drug resistance testing as programs mature and as HIV clinical management becomes more complex. African-owned research initiatives have helped to develop affordable resistance testing appropriate for use in the region, and have developed delivery models for resistance testing at different levels of the public health system. Some upper-middle-income countries such as Botswana and South Africa have introduced drug resistance testing for selected patient groups to guide clinical management. The scale-up of resistance testing will require substantial expansion of clinical and laboratory capacity in the region, but the expertise and resources exist in Africa to support this. The long-term population health impact and cost-effectiveness of resistance testing in the region will also require further investigation.

Background: Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation. Determining definitive outcomes of these lost patients, and the effects of losses to follow-up on estimates of survival and risk factors for death after HAART, are key to monitoring the effectiveness of global HAART scale-up efforts. Methodology/Principal Findings: A cohort study comparing clinical outcomes and risk factors for death after HAART initiation as reported before and after tracing of patients lost to follow-up was conducted in Botswana’s National Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting for HAART were evaluated. The main outcome measures were death or loss to follow-up within the first year after HAART initiation. Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88–0.94 before tracing and 0.83 (95% confidence interval, 0.79–0.86) after tracing, log rank P,0.001]. In addition, a significantly increased risk of death after HAART among men [adjusted hazard ratio 1.74 (95% confidence interval, 1.05–2.87)] would have been missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence interval, 0.65–3.05)]. Conclusions/Significance: Due to high rates of death among patients lost to follow-up after HAART, survival rates may be inaccurate and important risk factors for death may be missed if patients are not actively traced. Patient tracing and uniform reporting of outcomes after HAART are needed to enable accurate monitoring of global HAART scale-up efforts.

Adherence to antiretroviral therapy among HIV patients is the most important patient-enabled factor related to virological failure and can lead to drug resistance. It is important to avoid virological failure, especially in resource-limited settings where treatment options are limited and the effects of treatment failure are profound. This qualitative study aimed to identify the psycho-social factors related to adherence behaviour in Gaborone, Botswana, a high prevalence setting in southern Africa. One-to-one, in-depth interviews were conducted with adult antiretroviral patients in the private and public health sectors who had been on antiretroviral therapy for a minimum of 6 months. A grounded theory approach was adopted and patients were selected purposively and theoretical sampling determined the final sample size. Thirty-two patients were interviewed, 22 from the public-sector, the mean age was 9.5 years and 53% were women. We found that acceptance of HIV-status, the ability to avoid internalising stigmatising attitudes and identification of an encouraging confidante were key factors related to good adherence. Encouraging confidantes (including clinicians) and contributed to promoting hope and acceptance of HIV-status, enabling patients to develop a positive therapeutic relationship with their antiretrovirals and make lifestyle changes that promoted adherence. Active participation in a social network and a desire to avoid being thin and visibly identifiable as HIV-positive were also adherence-motivating factors. Conversely, participants who expressed some degree of denial about their HIV-status tended to express emotions associated with depression, and internalised stigma that inhibited the development of a relationship with a confidante. We feel it is important to identify individuals with HIV who are still in some degree of denial about their status and to identify depression among patients on antiretrovirals. This will enable more targeted, individualised support in the management of individuals' HIV disease.

We analyzed the reverse transcriptase genotypes of human immunodeficiency virus type 1 subtype C viruses isolated from 23 patients in Botswana treated with didanosine-based regimens. The K65R mutation was selected either alone or together with the Q151M, S68G, or F116Y substitution in viruses from seven such individuals. The results of in vitro passage experiments were consistent with an apparent increased propensity of subtype C viruses to develop the K65R substitution.

Corrigendum to: ‘‘The relationship of acceptance or denial of HIV-status to antiretroviral adherence among adult HIV patients in urban Botswana’’ [Soc. Sci. Med. 67 (2008) 301–310] Sara L. Nam*, Katherine Fielding , Ava Avalos , Diana Dickinson , Tendani Gaolathe , P. Wenzel Geissler d a London School of Hygiene and Tropical Medicine, Infectious Diseases Epidemiology Unit, Keppel Street, London WC1E 7HT, UK Ministry of Health, Adult Infectious Diseases Care Centre, Princess Marina Hospital, Gaborone, Botswana c Primary Health Care, Independence Surgery, Gaborone, Botswana d London School of Hygiene and Tropical Medicine, Health Policy Unit, London, UK

Objective Our objective was to establish genotypic resistance profiles among the 4% of Batswana patients who experienced virologic failure while being followed within Botswana's National Antiretroviral Treatment Program between 2002 and 2007. Methods At the beginning of the national program in 2002, almost all patients received stavudine (d4T), together with didanosine (ddI), as part of their first nucleoside reverse transcriptase inhibitor (NRTI)-based regimen (Group 1). In contrast, the standard of care for all patients subsequently enrolled (2002-2007) included zidovudine/lamivudine (ZDV/3TC) (Group 2). Genotypes were analyzed in 26 patients from Group 1 and 37 patients from Group 2. Associations between mutations were determined using Pearson's correlation coefficient and Jaccard's coefficient of similarity. Results Seventy-eight percent of genotyped patients possessed mutations associated with protease inhibitor (PI) resistance while 87% and 90%, respectively, exhibited mutations associated with NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most frequent PI mutations involving resistance to NFV were L90M (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N were often observed in tandem (P = 60.5, J = 50; p = 0.002; Group 2) alongside Q61E in 42.8% of patients who received ZDV/3TC. Both major patterns of thymidine analogue mutations, TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1 and 2, although M184V was higher among individuals who had initially received ddI (61% versus 40.5%). In contrast, L74V was more frequent among individuals from Group 2 (16.2% versus 7.7%). Differences in regard to NNRTI mutations were also observed between Group 1 and Group 2 patients. Conclusion Despite a low rate of therapeutic failure (4%) among these patients, those who failed possessed high numbers of resistance mutations as well as novel resistance mutations and/or polymorphisms at sites within reverse transcriptase and protease.