Dolutegravir HIV drug resistance (HIVDR) data from Africa remain sparse. We reviewed HIVDR results of Malawians on dolutegravir-based antiretroviral therapy (November 2020–September 2021). Of 6462 eligible clients, 33 samples were submitted to South Africa, 27 were sequenced successfully, and 8 (30%) had dolutegravir HIVDR. Malawi urgently requires adequate HIVDR testing capacity.
Background: Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum. Methods: 1–6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014–2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management. Results: 596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p<0.01), had higher parity (p = 0.03) and more likely to have undetectable VL at enrollment than those lost to follow-up (80.0% vs 70.2%, p<0.01). Of 590 women on ART (median 30.1 months; inter-quartile range 26.8–61.3), 442 (74.9%) with complete VL data at 3 visits were included in further analysis. Prevalence of detectable VL at 12 and 24 months was higher among women with detectable VL at enrollment than among those with undetectable VL (74 detectable VL results/66 women vs. 19/359; p<0.001). In multivariable analysis (adjusted for age, parity, education, partner disclosure, timing of ART start and self-reported adherence), detectable VL at 24 months was 9 times more likely among women with 1 prior detectable VL (aOR 9.0; 95%CI 3.5–23.0, p<0.001) and 226 times more likely for women with 2 prior detectable VLs (aOR 226.4; 95%CI 73.0–701.8, p<0.001). Conclusions: Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.
In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).
Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.
An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described. Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation. Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART. In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.
Background: The prevalence of Human Immunodeficiency Virus (HIV) among prisoners remains high in many countries, especially in Africa, despite a global decrease in HIV incidence. Programs to reach incarcerated populations with HIV services have been implemented in Malawi, but the success of these initiatives is uncertain. We explored which challenges prisoners face in receiving essential HIV services and whether HIV risk behavior is prevalent in prisons. Methods: We conducted a mixed-methods (qualitative and quantitative), cross-sectional study in 2018 in six prisons in Southern Malawi, two large central prisons with on-site, non-governmental organization (NGO) supported clinics and 4 smaller rural prisons. Four hundred twelve prisoners were randomly selected and completed a structured questionnaire. We conducted in-depth interviews with 39 prisoners living with HIV, which we recorded, transcribed and translated. We used descriptive statistics and logistic regression to analyze quantitative data and content analysis for qualitative data. Results: The majority of prisoners (93.2%) were male, 61.4% were married and 63.1% were incarcerated for 1–5 years. Comprehensive services were reported to be available in the two large, urban prisons. Female prisoners reported having less access to general medical services than males. HIV risk behavior was reported infrequently and was associated with incarceration in urban prisons (adjusted odds ratio [aOR] 18.43; 95% confidence interval [95%-CI] 7.59–44.74; p = < 0.001) and not being married (aOR 17.71; 95%-CI 6.95–45.13; p = < 0.001). In-depth interviews revealed that prisoners living with HIV experienced delays in referrals for more severe illnesses. Prisoners emphasized the detrimental impact of poor living conditions on their personal health and their ability to adhere to antiretroviral therapy (ART). Conclusions: Malawian prisoners reported adequate knowledge about HIV services albeit with gaps in specific areas. Prisoners from smaller, rural prisons had suboptimal access to comprehensive HIV services and female prisoners reported having less access to health care than males. Prisoners have great concern about their poor living conditions affecting general health and adherence to ART. These findings provide guidance for improvement of HIV services and general health care in Malawian institutionalized populations such as prisoners.