Background. Adverse pregnancy outcomes such as preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) remain major global problems. We compared pregnancy outcomes among HIV-infected women receiving antiretroviral treatment (ART) and with CD4 ≥350 cells, and HIV-uninfected women to assess if disparities associated with HIV infection have been eliminated through use of ART. Setting: Observational study conducted at five health facilities in Blantyre, Malawi during 2016–2017. Methods. HIV-infected women receiving the national ART regimen (efavirenz+lamuvidine+tenfovir) and HIV-uninfected women were consented and enrolled at delivery. Data collected included sociodemographic and clinical; gestational age (GA); birth weight (BW); infant/maternal anthropometry; and laboratory results. We defined PTB as GA<37 weeks; LBW as BW <2·5 kg; and SGA as BW <10th percentile of GA. SGA infants were classified into proportionate and disproportionate based on ponderal index. Descriptive, stratified and multivariate logistic and linear regression analyses were used. Results. Of 5423 women approached, 614 HIV-infected and 685 HIV-uninfected women were enrolled. Rates of PTB, LBW and SGA were 10·6%, 7·2% and 17·1% among HIV-infected women on ART and 9·5%, 5·0%, and 18·4% among HIV-uninfected women, respectively. None of these differences were statistically significant in univariate or multivariate adjusted analyses (P>0·05). Of 231 SGA infants, 78·8% were proportionate and 21% were disproportionate. Of the 614 HIV-infected women on ART, 75% had undetectable virus at delivery. Conclusion. ART use has reduced the high rates of adverse pregnancy outcomes among HIV-infected women. However, the rates remain high irrespective of HIV infection and require appropriate interventions.

Background Compared to the abundance of clinical, molecular, and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Methods We enrolled a cohort of patients with PCR confirmed COVID-19 disease at Queen Elizabeth Central Hospital, the main hospital for southern Malawi, between July 2020 and September 2021. The recruitment period covered three waves of SARS-CoV-2 infections in Malawi. Clinical and diagnostic data were collected using the ISARIC clinical characterization protocol for COVID-19. The viral material from PCR-positive swabs was amplified with a tiling PCR scheme and sequenced using the MinION sequencer in Malawi. Consensus genomes were generated using the ARTIC pipeline and lineage assignment was performed using Pangolin. Results Sequencing data showed that wave one was predominantly B.1 (8/11 samples), wave two consisted entirely of Beta variant of concern (VOC) (6/6), and wave three was predominantly Delta VOC (25/26). Patients presenting in the second and third waves had progressively fewer underlying chronic conditions, and patients in the third wave had a shorter time to presentation (2 days vs 5 in the original wave). Multivariable logistic regression demonstrated increased mortality in wave three, dominated by the Delta VOC, compared to previous waves (OR 6.6 [CI 1.1-38.8]). Conclusions Patients hospitalised with COVID-19 in Blantyre during the Delta wave had more acute symptom onset; fewer underlying conditions; and were more likely to die. Whilst we demonstrate the value of linking virus sequence data with clinical outcome data in a low-income setting, this study also highlights the considerable barriers to establishing sequencing capacity in a setting heavily affected by disruptions in supply chain and inequity of resource distribution.

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4 T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery. Methods: Women with pre-ART CD4 cell counts ≥350 cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post-hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat. Findings: 1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4 count 728 cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p=0·37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p=0·01). The arms did not differ with respect to the rate of grade 2, 3 or 4 safety events (p=0·61). Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4 cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

Background Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome. Methods We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinION™ in Blantyre. Results We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p < 0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p < 0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0–25.0 p = 0.05) compared to the first wave of infection. Conclusions Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave.

Background Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens. Methods In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation. Results Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0–2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06–.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06–1.70]). Conclusions Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.