A mixed methods approach identifying facilitators and barriers to guide adaptations to InterCARE strategies: an integrated HIV and hypertension care model in Botswana.

BACKGROUND: Botswana serves as a model of success for HIV with 95% of people living with HIV (PLWH) virally suppressed. Yet, only 19% of PLWH and hypertension have controlled blood pressure. To address this gap, InterCARE, a care model that integrates HIV and hypertension care through a) provider training; b) adapted electronic health record; and c) treatment partners (peer support), was designed. This study presents results from our baseline assessment of the determinants and factors used to guide adaptations to InterCARE implementation strategies prior to a hybrid type 2 effectiveness-implementation study. METHODS: This study employed a convergent mixed methods design across two clinics (one rural, one urban) to collect quantitative and qualitative data through facility assessments, 100 stakeholder surveys (20 each PLWH and hypertension, existing HIV treatment partners, clinical healthcare providers (HCPs), and 40 community leaders) and ten stakeholder key informative interviews (KIIs). Data were analyzed using descriptive statistics and deductive qualitative analysis organized by the Consolidated Framework for Implementation Research (CFIR) and compared to identify areas of convergence and divergence. RESULTS: Although 90.3% of 290 PLWH and hypertension at the clinics were taking antihypertensive medications, 52.8% had uncontrolled blood pressure. Results from facility assessments, surveys, and KIIs identified key determinants in the CFIR innovation and inner setting domains. Most stakeholders (> 85%) agreed that InterCARE was adaptable, compatible and would be successful at improving blood pressure control in PLWH and hypertension. HCPs agreed that there were insufficient resources (40%), consistent with facility assessments and KIIs which identified limited staffing, inconsistent electricity, and a lack of supplies as key barriers. Adaptations to InterCARE included a task-sharing strategy and expanded treatment partner training and support. CONCLUSIONS: Integrating hypertension services into HIV clinics was perceived as more advantageous for PLWH than the current model of hypertension care delivered outside of HIV clinics. Identified barriers were used to adapt InterCARE implementation strategies for more effective intervention delivery. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT05414526 . Registered 18 May 2022 - Retrospectively registered.

Cultural adaption, translation, preliminary reliability and validity of psychological and behavioural measures for adolescents living with HIV in Botswana: A multi-stage approach.

Human immunodeficiency virus (HIV) remains a significant public health issue among young people living in Botswana. There is a need for reliable and valid psychological and behavioural measures of causally important constructs for this population. We developed a new HIV knowledge measure for use with 10-19-year-olds living with HIV and translated and adapted additional tools measuring HIV adjustment, HIV disclosure cognitions and affect, HIV communication beliefs, antiretroviral (ART) adherence, and self-esteem, using a multi-step process. This included (1) item generation for the HIV knowledge questionnaire, (2) translation including back-translation and expert review, (3) cognitive interviewing, (4) reliability testing (5) preliminary validity analysis. The HIV Knowledge Questionnaire for Adolescents living with HIV, the Illness Cognition Questionnaire, the Adolescent HIV Disclosure Cognition and Affect Scale, the HIV Communication Beliefs Scale, and the Rosenberg Self-Esteem Scale showed acceptable or good reliability and some evidence of validity for adolescents living with HIV in Botswana.

The role of migration networks in the development of Botswana's generalized HIV epidemic.

The majority of people with HIV live in sub-Saharan Africa, where epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, the role of population-level mobility in the development of generalized HIV epidemics has not been studied. Here we do so by studying historical migration data from Botswana, which has one of the most severe generalized HIV epidemics worldwide; HIV prevalence was 21% in 2021. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana's epidemic, the population was extremely mobile and the country was highly connected by substantial migratory flows. We test this mobility hypothesis by conducting a network analysis using a historical time series (1981-2011) of micro-census data from Botswana. Our results support our hypothesis. We found complex migration networks with very high rates of rural-to-urban, and urban-to-rural, migration: 10% of the population moved annually. Mining towns (where AIDS cases were first reported, and risk behavior was high) were important in-flow and out-flow migration hubs, suggesting that they functioned as 'core groups' for HIV transmission and dissemination. Migration networks could have dispersed HIV throughout Botswana and generated the current hyperendemic epidemic.

Over 25 million people in sub-Saharan Africa live with HIV. After reporting its first AIDS case in 1985, Botswana is one of the most severely affected countries in the region, with one in five adults now living with HIV. Movement of the population is likely to have contributed to a geographically dispersed, and high-prevalence, HIV epidemic in Botswana. Since 1985, urbanization, rapid economic and population growth, and migration have transformed Botswana. Yet, few studies have analyzed the role of population-level movement patterns in the spread of HIV during this time. By studying micro-census data from Botswana between 1981 and 2011, Song et al. found that the country's population was highly mobile during this period. Reconstructions of internal migration patterns show very high rates of rural-to-urban and urban-to-rural migration, with 10% of Botswana's population moving each year. The first reported AIDS cases in Botswana occurred in mining towns and cities where high-risk behavior was prevalent. These areas were also migration hubs during this period and could have contributed to the rapid spread of HIV throughout the country as infected individuals moved back to rural districts. Understanding human migration patterns and how they affect the spread of infectious diseases using current data could help public health authorities in Botswana and additional sub-Saharan African countries design control strategies for HIV and other important infections that occur in the region.

Population mobility and the development of Botswana's generalized HIV epidemic: a network analysis.

The majority of people with HIV live in sub-Saharan Africa, where HIV epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, population-level mobility has not yet been studied in the context of the development of generalized HIV epidemics. Here we do so by studying historical migration data from Botswana which has one of the most severe generalized HIV epidemics worldwide; in 2021, HIV prevalence was 21%. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana's epidemic, the population was highly mobile and there were substantial urban-to-rural and rural-to-urban migratory flows. We test this hypothesis by conducting a network analysis using a historical time series (1981 to 2011) of micro-census data from Botswana. We found 10% of the population moved their residency annually, complex migration networks connected urban with rural areas, and there were very high rates of rural-to-urban migration. Notably, we also found mining towns were both important in-flow and out-flow migration hubs; consequently, there was a very high turnover of residents in towns. Our results support our hypothesis, and together, provide one explanation for the development of Botswana's generalized epidemic.

Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020.

Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic.

The potential impact of country-level migration networks on HIV epidemics in sub-Saharan Africa: the case of Botswana.

Generalised HIV epidemics in sub-Saharan Africa show substantial geographical variation in prevalence, which is considered when designing epidemic control strategies. We hypothesise that the migratory behaviour of the general population of countries in sub-Saharan Africa could have a substantial effect on HIV epidemics and challenge the elimination effort. To test this hypothesis, we used census data from 2017 to identify, construct, and visualise the migration network of the population of Botswana, which has one of the most severe HIV epidemics worldwide. We found that, over 12 months, approximately 14% of the population moved their residency from one district to another. Four types of migration occurred: urban-to-urban, rural-to-urban, urban-to-rural, and rural-to-rural. Migration is leading to a marked geographical redistribution of the population, causing high rates of population turnover in some areas, and further concentrating the population in urban areas. The migration network could potentially be having a substantial effect on the HIV epidemic of Botswana: changing the location of high-transmission areas, generating cross-country transmission corridors, creating source-sink dynamics, and undermining control strategies. Large-scale migration networks could present a considerable challenge to eliminating HIV in Botswana and in other countries in sub-Saharan Africa, and should be considered when designing epidemic control strategies.

Outcomes of the Botswana national HIV/AIDS treatment programme from 2002 to 2010: a longitudinal analysis.

BACKGROUND: Short-term mortality rates among patients with HIV receiving antiretroviral therapy (ART) in sub-Saharan Africa are higher than those recorded in high-income countries, but systematic long-term comparisons have not been made because of the scarcity of available data. We analysed the effect of the implementation of Botswana's national ART programme, known as Masa, from 2002 to 2010. METHODS: The Masa programme started on Jan 21, 2002. Patients who were eligible for ART according to national guidelines had their data collected prospectively through a clinical information system developed by the Botswana Ministry of Health. A dataset of all available electronic records for adults (≥18 years) who had enrolled by April 30, 2010, was extracted and sent to the study team. All data were anonymised before analysis. The primary outcome was mortality. To assess the effect of loss to follow-up, we did a series of sensitivity analyses assuming varying proportions of the population lost to follow-up to be dead. FINDINGS: We analysed the records of 126,263 patients, of whom 102,713 had documented initiation of ART. Median follow-up time was 35 months (IQR 14-56), with a median of eight follow-up visits (4-14). 15,270 patients were deemed lost to follow-up by the end of the study. 63% (78,866) of the study population were women; median age at baseline was 34 years for women (IQR 29-41) and 38 years for men (33-45). 10,230 (8%) deaths were documented during the 9 years of the study. Mortality was highest during the first 3 months after treatment initiation at 12·8 deaths per 100 person-years (95% CI 12·4-13·2), but decreased to 1·16 deaths per 100 person-years (1·12-1·2) in the second year of treatment, and to 0·15 deaths per 100 person-years (0·09-0·25) over the next 7 years of follow-up. In each calendar year after the start of the Masa programme in 2002, average CD4 cell counts at enrolment increased (from 101 cells/µL [IQR 44-156] in 2002, to 191 cells/µL [115-239] in 2010). In each year, the proportion of the total enrolled population who died in that year decreased, from 63% (88 of 140) in 2002, to 0·8% (13 of 1599) in 2010. A sensitivity analysis assuming that 60% of the population lost to follow-up had died gave 3000 additional deaths, increasing overall mortality from 8% to 11-13%. INTERPRETATION: The Botswana national HIV/AIDS treatment programme reduced mortality among adults with HIV to levels much the same as in other low-income or middle-income countries. FUNDING: The African Comprehensive HIV/AIDS Partnerships.

Immunohaematological reference values for HIV-negative healthy adults in Botswana.

BACKGROUND: Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers' kits and textbooks. OBJECTIVES: The aim of this study was to determine the means, medians, 2.5th and 97.5th percentile reference intervals, for normal immunohaematological values in healthy adults in Botswana. METHOD: A total of 261 healthy participants comprising 126 men (48%) and 135 (52%) women were enrolled in the southern part of Botswana, and immunological and haematological laboratory parameters were measured. RESULTS: The mean age was 28.8 (95% Confidence Interval [CI] 27.7-29.8) years, with a median of 27 years and a range 18-66 years. The mean haemoglobin level was significantly lower for women (12.4 g/dL; 95% CI 12.1% - 12.7%) than men (15.1 g/dL; 95% CI 14.9% - 15.3%). The women's haemoglobin reference values (9.0 g/dL - 15.0 g/dL) levels were lower than observed in predominantly White populations (12.0 g/dL - 16.0 g/dL), but comparable with regional consensus reference intervals (9.5 g/dL - 15.8 g/dL) recently defined for East and Southern Africa. CONCLUSION: The established values provide an important tool for patient management and could influence decisions on inclusion of participants and adverse events in clinical trials conducted locally.

Immunohaematological reference values for HIV-negative healthy adults in Botswana.

BACKGROUND: Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers' kits and textbooks. OBJECTIVES: The aim of this study was to determine the means, medians, 2.5th and 97.5th percentile reference intervals, for normal immunohaematological values in healthy adults in Botswana. METHOD: A total of 261 healthy participants comprising 126 men (48%) and 135 (52%) women were enrolled in the southern part of Botswana, and immunological and haematological laboratory parameters were measured. RESULTS: The mean age was 28.8 (95% Confidence Interval [CI] 27.7-29.8) years, with a median of 27 years and a range 18-66 years. The mean haemoglobin level was significantly lower for women (12.4 g/dL; 95% CI 12.1% - 12.7%) than men (15.1 g/dL; 95% CI 14.9% - 15.3%). The women's haemoglobin reference values (9.0 g/dL - 15.0 g/dL) levels were lower than observed in predominantly White populations (12.0 g/dL - 16.0 g/dL), but comparable with regional consensus reference intervals (9.5 g/dL - 15.8 g/dL) recently defined for East and Southern Africa. CONCLUSION: The established values provide an important tool for patient management and could influence decisions on inclusion of participants and adverse events in clinical trials conducted locally.

Prevalence of transmitted HIV drug resistance in Botswana: lessons learned from the HIVDR-Threshold Survey conducted among women presenting for routine antenatal care as part of the 2007 national sentinel survey.

The emergence and spread of transmitted drug resistance (TDR) poses a major threat to the success of the rapidly expanding antiretroviral treatment (ART) programs in resource-limited countries. The World Health Organization recommends the use of the HIV Drug Resistance Threshold Survey (HIVDR-TS) as an affordable means to monitor the presence of TDR in these settings. We report our experiences and results of the 2007 HIVDR-TS in Botswana, a country with one of the longest-existing national public ART programs in Africa. The HIVDR-TS and HIV-1 incidence testing were performed in the two largest national sites as part of the 2007 antenatal Botswana Sentinel Survey. The HIVDR-TS showed no significant drug resistance mutations (TDR less than 5%) in one site. TDR prevalence, however, could not be ascertained at the second site due to low sample size. The agreement between HIVDR-TS eligibility criteria and laboratory-based methodologies (i.e., BED-CEIA and LS-EIA) in identifying recently HIV-1 infected adults was poor. Five years following the establishment of Botswana's public ART program, the prevalence of TDR remains low. The HIVDR-TS methodology has limitations for low-density populations as in Botswana, where the majority of antenatal sites are too small to recruit sufficient numbers of patients. In addition, the eligibility criteria (age <25 years and parity (first pregnancy)) of the HIVDR-TS performed poorly in identifying recent HIV-1 infections in Botswana. An alternative sampling strategy should be considered for the surveillance of HIVDR in Botswana and similar geographic settings.

Quantitation of human immunodeficiency virus type 1 viral load in plasma using reverse transcriptase activity assay at a district hospital laboratory in Botswana: a decentralization pilot study.

Roche COBAS Amplicor monitor version 1.5 assay is considered gold standard for viral load monitoring in Botswana. Due to its demand for elaborate infrastructure, viral load testing has been confined to the national HIV reference laboratories. Cavidi ExaVir Load version 2 assay was considered as a potential alternative to decentralize viral load testing to the rural/remote hospital laboratories and thus increase access to therapy. This study compared the performance of ExaVir Load v2 assay at a district hospital laboratory in Serowe and COBAS Amplicor monitor v1.5 assay at the Botswana Harvard HIV Reference Laboratory using quality assessment samples and plasma from HIV-positive individuals. ExaVir Load v2 and COBAS Amplicor monitor v1.5 assays had very good agreement; Kappa statistic 0.951. The COBAS Amplicor monitor v1.5 and ExaVir Load v2 assays detected HIV-1 RNA in 84 and 86 samples but did not detect HIV-1 RNA in 221 and 219 samples, respectively. The two assays detected HIV-1 RNA concordantly in 82 samples and were strongly correlated (r=0.8554, P<0.0001). ExaVir Load v2 assay provided a simple and reliable alternative viral load system that is adaptable to district hospital laboratories. The cost per test is less than RT-PCR. The ExaVir Load v2 systems have since been placed in four more district and primary hospital laboratories.

Five-year outcomes of initial patients treated in Botswana's National Antiretroviral Treatment Program.

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.

Early diagnosis of human immunodeficiency virus in infants using polymerase chain reaction on dried blood spots in Botswana's national program for prevention of mother-to-child transmission.

BACKGROUND: Botswana has high antenatal human immunodeficiency virus (HIV) prevalence (33.4%). The public health system provides free services for prevention of mother to child transmission of HIV (PMTCT) and antiretroviral therapy, which can reduce vertical HIV transmission from 35% to <5%. Infant HIV diagnosis is challenging in resource-limited settings, and HIV prevalence among HIV-exposed infants in Botswana is unknown. Dried blood spot (DBS) polymerase chain reaction (PCR) provides a feasible method to assess PMTCT programs and identify HIV-infected children. METHODS: We trained staff in 15 clinics and a hospital to obtain DBS on HIV-exposed infants age 6 weeks to 17 months receiving routine care. Samples were sent to the national HIV reference laboratory. Roche Amplicor 1.5 DNA PCR testing was performed. RESULTS: Between June-December 2005, 1931 HIV-exposed infants age 6 weeks to 17 months were tested for HIV, of whom 136 (7.0%) were HIV infected. Among infants

Public-private options for expanding access to human resources for HIV/AIDS in Botswana.

In responding to the goal of rapidly increasing access to antiretroviral treatment (ART), the government of Botswana undertook a major review of its health systems options to increase access to human resources, one of the major bottlenecks preventing people from receiving treatment. In mid-2004, a team of government and World Health Organization (WHO) staff reviewed the situation and identified a number of public sector scale up options. The team also reviewed the capacity of private practitioners to participate in the provision of ART. Subsequently, the government created a mechanism to include private practitioners in rolling out ART. At the end of 2006, more than 4500 patients had been transferred to the private sector for routine follow up. It is estimated that the cooperation reduced the immediate need for recruiting up to 40 medically qualified staff into the public sector over the coming years, depending on the development of the national standard for the number and duration of patient visits to a doctor per year. Thus welcome relief was brought, while at the same time not exercising a pull factor on human resources for health in the sub-Saharan region.

Successful introduction of routine opt-out HIV testing in antenatal care in Botswana.

BACKGROUND: Botswana has high HIV prevalence among pregnant women (37.4% in 2003) and provides free services for prevention of mother-to-child transmission (PMTCT) of HIV. Nearly all pregnant women (>95%) have antenatal care (ANC) and deliver in hospital. Uptake of antenatal HIV testing was low from 1999 through 2003. In 2004, Botswana's President declared that HIV testing should be "routine but not compulsory" in medical settings. METHODS: Health workers were trained to provide group education and recommend HIV testing as part of routine ANC services. Logbook data on ANC attendance, HIV testing, and uptake of PMTCT interventions were reviewed before and after routine testing training, and ANC clients were interviewed. RESULTS: After routine testing started, the percentage of all HIV-infected women delivering in the regional hospital who knew their HIV status increased from 47% to 78% and the percentage receiving PMTCT interventions increased from 29% to 56%. ANC attendance and the percentage of HIV-positive women who disclosed their HIV status to others remained stable. Interviews indicated that ANC clients supported the policy. CONCLUSIONS: Routine HIV testing was more accepted than voluntary testing in this setting and led to substantial increases in the uptake of testing and PMTCT interventions without detectable adverse consequences. Routine testing in other settings may strengthen HIV care and prevention efforts.

Two and a half years of routine HIV testing in Botswana.

BACKGROUND: Botswana was the first African country to introduce routine HIV testing (RHT). OBJECTIVE: To report program data for the first 2.5 years of RHT. METHODS: RHT was introduced in 2004. Rapid HIV tests were introduced later the same year and are widely available. The main criteria for RHT are symptoms of HIV/AIDS, pregnancy, sexually transmitted infection, and attendance for medical examination. Testing may also be self-initiated. FINDINGS: There has been a rapid scale-up of RHT. A total of 60,846 persons were tested through RHT in 2004 versus 157,894 in 2005 and 88,218 in the first half of 2006. Testing rates in the population through RHT were 40 per 1000 persons, 93 per 1000 persons, and 104 per 1000 persons, respectively. In 2005, 89% of those offered testing accepted, with 69% of those tested being female and 31% male. The proportion of men who tested HIV-positive was 34% versus 30% for women. The main reasons for testing in 2005 were patient's wish (50%), pregnancy (25%), medical examination (7%), clinical suspicion (6%), and sexually transmitted infection (2%). Attendance at voluntary counseling and testing centers has increased parallel to the scale-up of RHT. CONCLUSIONS: RHT has been widely accepted by the population, and no adverse effects or instances have been reported. It has provided increased access to preventive services and earlier assessment for antiretroviral treatment. We believe the benefits of RHT clearly outweigh the risks.