Poloko Kebaabetswe

Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana

BACKGROUND Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

Barriers to Antiretroviral Adherence for Patients Living with HIV Infection and AIDS in Botswana

Background: Botswana has the highest rate of HIV infection in the world, estimated at 36% among the population aged 15‐49 years. To improve antiretroviral (ARV) treatment delivery, we conducted a cross‐sectional study of the social, cultural, and structural determinants of treatment adherence. Methods: We used both qualitative and quantitative research methodologies, including questionnaires and interviews with patients receiving ARV treatment and their health care providers to elicit principal barriers to adherence. Patient report and provider estimate of adherence (≥95% doses) were the primary outcomes. Results: One hundred nine patients and 60 health care providers were interviewed between January and July 2000; 54% of patients were adherent by self‐report, while 56% were adherent by provider assessment. Observed agreement between patients and providers was 68%. Principal barriers to adherence included financial constraints (44%), stigma (15%), travel/migration (10%), and side effects (9%). On the basis of logistic regression, if cost were removed as a barrier, adherence is predicted to increase from 54% to 74%. Conclusions: ARV adherence rates in this study were comparable with those seen in developed countries. As elsewhere, health care providers in Botswana were often unable to identify which patients adhere to their ARV regimens. The cost of ARV therapy was the most significant barrier to adherence.

Male circumcision: an acceptable strategy for HIV prevention in Botswana.

Background: Male circumcision is known to reduce the risk of acquiring HIV, but few studies have been performed to assess its acceptability among either children or adults in sub-Saharan Africa. Methods: We conducted a cross sectional survey in nine geographically representative locations in Botswana to determine the acceptability of male circumcision in the country, as well as the preferred age and setting for male circumcision. Interviews were conducted using standardised questionnaires both before and after an informational session outlining the risks and benefits of male circumcision. Results: Among 605 people surveyed, the median age was 29 years (range 18–74 years), 52% were male, and >15 ethnicities were represented. Before the informational session, 408 (68%) responded that they would definitely or probably circumcise a male child if circumcision was offered free of charge in a hospital setting; this number increased to 542 (89%) after the informational session. Among 238 uncircumcised men, 145 (61%) stated that they would definitely or probably get circumcised themselves if it were offered free of charge in a hospital setting; this increased to 192 (81%) after the informational session. In a multivariate analysis of all participants, people with children were more likely to favour circumcision than people without children (adjusted odds ratio 1.8, 95% CI 1.0 to 3.4). Most participants (55%) felt that the ideal age for circumcision is before 6 years, and 90% of participants felt that circumcision should be performed in the hospital setting. Conclusions: Male circumcision appears to be highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy among sexually active people is supported by clinical trials.

Acceptability of infant male circumcision as part of HIV prevention and male reproductive health efforts in Gaborone, Botswana, and surrounding areas.

Adult male circumcision reduces a man’s risk for heterosexual HIV acquisition. Infant circumcision is safer, easier and less costly but not widespread in southern Africa. Questionnaires were administered to sixty mothers of newborn boys in Botswana: 92% responded they would circumcise if the procedure were available in a clinical setting, primarily to prevent future HIV infection, and 85% stated the infant’s father must participate in the decision. Neonatal male circumcision appears to be acceptable in Botswana and deserves urgent attention in resource-limited regions with high HIV prevalence, with the aim to expand services in safe, culturally acceptable and sustainable ways.

A randomized trial of Mogen clamp versus Plastibell for neonatal male circumcision in Botswana.

Background:Male circumcision can reduce the risk of heterosexually acquired HIV-1 infection in men. Neonatal male circumcision (NMC) has many potential advantages over circumcision at older ages, but little is known about its feasibility and safety in resource-limited settings. Methods:We performed a randomized trial in southeastern Botswana of Mogen clamp and Plastibell, 2 commonly used devices for NMC. Follow-up visits occurred at 6 weeks and 4 months postpartum. Adverse events, parental satisfaction, and staff impressions were recorded. Results:Of 302 male neonates randomized, 300 (99%) underwent circumcision, 153 (51%) with Mogen clamp, and 147 (49%) with Plastibell. There were no major adverse events in the Mogen clamp arm, but there were 2 major adverse events in the Plastibell arm (both were a proximally migrated ring that had to be removed by study staff). Minor adverse events were more common with the Mogen clamp compared with the Plastibell, specifically removal of too little skin and formation of skin bridges or adhesions (12 versus 1 and 11 versus 3, respectively, all P < 0.05). Five (3%) infants in the Mogen clamp arm and none in the Plastibell arm had minor bleeding (P = 0.03). More than 94% of mothers reported being highly or completely satisfied with the procedure. Conclusions:NMC can be performed in Botswana with a low rate of adverse events and high parental satisfaction. Although the risk of migration and retention of the Plastibell is small, the Mogen clamp may be safer for NMC in regions where immediate emergent medical attention is not available.

Trends and determinants of survival for over 200 000 patients on antiretroviral treatment in the Botswana National Program: 2002–2013

Objectives:To determine the incidence and risk factors of mortality for all HIV-infected patients receiving antiretroviral treatment at public and private healthcare facilities in the Botswana National HIV/AIDS Treatment Programme. Design:We studied routinely collected data from 226 030 patients enrolled in the Botswana National HIV/AIDS Treatment Programme from 2002 to 2013. Methods:A person-years (P-Y) approach was used to analyse all-cause mortality and follow-up rates for all HIV-infected individuals with documented antiretroviral therapy initiation dates. Marginal structural modelling was utilized to determine the effect of treatment on survival for those with documented drug regimens. Sensitivity analyses were performed to assess the robustness of our results. Results:Median follow-up time was 37 months (interquartile range 11–75). Mortality was highest during the first 3 months after treatment initiation at 11.79 (95% confidence interval 11.49–12.11) deaths per 100 P-Y, but dropped to 1.01 (95% confidence interval 0.98–1.04) deaths per 100 P-Y after the first year of treatment. Twelve-month mortality declined from 7 to 2% of initiates during 2002–2012. Tenofovir was associated with lower mortality than stavudine and zidovudine. Conclusion:The observed mortality rates have been declining over time; however, mortality in the first year, particularly first 3 months of antiretroviral treatment, remains a distinct problem. This analysis showed lower mortality with regimens containing tenofovir compared with zidovudine and stavudine. CD4+ cell count less than 100 cells/&mgr;l, older age and being male were associated with higher odds of mortality.

“The keeping is the problem”: A qualitative study of IRB-member perspectives in Botswana on the collection, use, and storage of human biological samples for research

BackgroundConcurrent with efforts to establish national and regional biorepositories in Africa is widespread endorsement of ethics committees as stewards of the interests of individual donors and their communities. To date, ethics training programs for IRB members in Botswana have focused on ethical principles and international guidelines rather than on the ethical dimensions of specific medical technologies and research methodologies. Little is known about the knowledge and concerns of current and prospective IRB members in Botswana with respect to export, reuse, storage, and benefit-sharing of biospecimens.MethodsThis qualitative study examined perspectives of IRB members in Botswana about the collection and use of biospecimens in research. Forty-one IRB members representing five committees in Botswana participated in discussions groups in March 2013. Transcriptions of audiotapes and field notes were analyzed to identify issues of concern that might be alleviated through education and capacity-building, and areas that required ongoing discussion or additional regulatory guidance.ResultsAreas of concern included lack of understanding among patients and providers about the use of biospecimens in clinical care and research; reuse of biospecimens, particularly issues of consent, ownership and decision-making; export of specimens and loss of control over reuse and potential benefits; and felt need for regulatory guidance and IRB-member training. Local belief systems about bodily integrity and strong national identity in the construct of benefits may be at odds with initiatives that involve foreign biorepositories or consider such collections to be global public goods.ConclusionEducation is needed to strengthen IRB-member capacity to review and monitor protocols calling for the collection and use of biospecimens, guided by clear national policy on priority-setting, partnerships, review, and oversight. Engagement with local stakeholders is needed to harmonize fundamentally different ways of understanding the human body and community identity with the aims of contemporary biomedicine.

Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana.

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants’ perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants’ knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Variation in attrition at subnational level: review of the Botswana National HIV/AIDS Treatment (Masa) programme data (2002-2013)

To evaluate the variation in all‐cause attrition [mortality and loss to follow‐up (LTFU)] among HIV‐infected individuals in Botswana by health district during the rapid and massive scale‐up of the National Treatment Program.

Rural exposure during medical education and student preference for future practice location - a case of Botswana

Background Botswana’s medical school graduated its first class in 2014. Given the importance of attracting doctors to rural areas the school incorporated rural exposure throughout its curriculum. Aim This study explored the impact of rural training on students’ attitudes towards rural practice. Setting The University of Botswana family medicine rural training sites, Maun and Mahalapye. Methods The study used a mixed-methods design. After rural family medicine rotations, third- and fifth-year students were invited to complete a questionnaire and semi-structured interview. Data were analysed using descriptive statistics and thematic analysis. Results The thirty-six participants’ age averaged 23 years and 48.6% were male. Thirty-three desired urban practice in a public institution or university. Rural training did not influence preferred future practice location. Most desired specialty training outside Botswana but planned to practice in Botswana. Professional stagnation, isolation, poorly functioning health facilities, dysfunctional referral systems, and perceived lack of learning opportunities were barriers to rural practice. Lack of recreation and poor infrastructure were personal barriers. Many appreciated the diversity of practice and supportive staff seen in rural practice. Several considered monetary compensation as an enticement for rural practice. Only those with a rural background perceived proximity to family as an incentive to rural practice. Conclusion The majority of those interviewed plan to practice in urban Botswana, however, they did identify factors that, if addressed, may increase rural practice in the future. Establishing systems to facilitate professional development, strengthening specialists support, and deploying doctors near their home towns are strategies that may improve retention of doctors in rural areas.