Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir- than with efavirenz-based antiretroviral therapy.

BACKGROUND: There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub-Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG). METHODS: We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana, excluding those with pre-existing diabetes. We screened for GDM using a 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks' gestation or at the earliest prenatal visit for those presenting after 28 weeks. Logistic regression models were fitted to assess the association between maternal HIV infection and GDM. Subgroup analyses were performed among WLHIV to assess the association between maternal antiretroviral therapy (ART) in pregnancy [DTG vs. efavirenz (EFV) with tenofovir/emtricitabine] and GDM. RESULTS: Of 486 pregnant women, 66.5% were WLHIV, and they were older than women without HIV (median age 30 vs. 25 years, P < 0.01). Among WLHIV, 97.8% had an HIV-1 RNA level < 400 copies/mL at enrolment. Overall, 8.4% had GDM with similar rates between WLHIV and those without HIV (9.0% vs. 7.4%). The WLHIV receiving DTG-based ART had a 60% lower risk for GDM compared with those on EFV-based ART (adjusted odds ratio = 0.40, 95% CI: 0.18-0.92) after adjusting for confounders. CONCLUSIONS: Pregnant WLHIV on ART in Botswana were not at increased risk of GDM compared with women without HIV. Among WLHIV, the risk of GDM was lower with DTG- than with EFV-based ART. Further studies with larger cohorts are warranted to confirm these findings.

Development and launch of the first obstetrics and gynaecology master of medicine residency training programme in Botswana.

BACKGROUND: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage. METHODS: We developed a 4-year OBGYN MMed programme at the University of Botswana (UB) using the Kern's approach. In-line with UB MMed standards, the programme includes clinical apprenticeship training complemented by didactic and research requirements. We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training. RESULTS: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The clinical rotations and curricular development have been rolled out successfully. The first round of continuous assessment of residents was performed and internal programme evaluation was conducted. The national accreditation process was initiated. CONCLUSION: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.

Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

BACKGROUND: The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS: We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS: The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS: All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Identification of primary HIV-1C infection in Botswana.

Methods for identification of primary HIV infections seem increasingly important to understand pathogenesis, and to prevent transmission, which is particularly efficient during acute infection. Most current algorithms for HIV testing are based on detection of HIV antibodies and are unable to identify early infections before seroconversion. The efficiency of prospective cohorts, which is a standard approach for identifying primary HIV-1 infection, depends on a variety of epidemiological and cultural factors including HIV incidence and stigma and, not surprisingly, varies significantly in different geographical areas. We report a voluntary counseling and testing (VCT)-based approach to identifying primary HIV-1C infection that was developed as part of a primary HIV-1 subtype C infection study in Botswana. The referral strategy was based on: (1) collaboration with VCT centers at city clinics operated by the Ministry of Health; (2) partnering with the busiest non-government VCT center; (3) educating healthcare workers and the community about primary HIV infection; and (4) pairing with diverse VCT providers, including NGOs and private-sector organizations. Acute HIV-1 infections were defined by a negative HIV-1 serology combined with a positive HIV-1 RT-PCR test. Recent HIV-1 infections were identified by detuned EIA testing according to the classic STARTH algorithm. The VCT-based referral strategy resulted in the successful identification of 57 cases of acute and early HIV infection. A referral strategy of expanded VCT with viral RNA (Ribonucleic acid) testing to a national program in Botswana may be a promising approach for identification of primary HIV infections on a countrywide level. The program should offer VCT with viral RNA testing to the general public, facilitate proper counseling and risk reduction, and allow initiation of early HAART, and may reduce new viral transmissions.

Effects of HIV-related stigma among an early sample of patients receiving antiretroviral therapy in Botswana.

Botswana, with its estimated HIV prevalence of 37%, instituted a policy of universal access to antiretroviral therapy (ART) in 2002. Initial enrolment lagged behind expectations, with a shortfall in voluntary testing that observers have attributed to HIV-related stigma - although there are no published data on stigma among HIV-positive individuals in Botswana. We interviewed 112 patients receiving ART in 2000, finding evidence of pervasive stigma in patterns of disclosure, social sequelae, and delays in HIV testing. Ninety-four percent of patients reported keeping their HIV status secret from their community, while 69% withheld this information even from their family. Twenty-seven percent of patients said that they feared loss of employment as a result of their HIV status. Forty percent of patients reported that they delayed getting tested for HIV; of these, 51% cited fear of a positive test result as the primary reason for delay in seeking treatment, which was often due to HIV-related stigma. These findings suggest that success of large-scale national ART programmes will require initiatives targeting stigma and its social, economic and political correlates.