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Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7-12) years, median duration of first -line ART 5.2(3.3-6.8) years; CD4 count 774 (528-1083) cells/mm3, weight-for-age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13-1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31-10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21-0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25-10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16-1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18-9.8, p = 0.023). Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.

Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes.

Background The aim of this study was to compare quantitative ultrasound (QUS) and dual energy X-ray absorptiometry (DXA) for determining bone mineral density (BMD) among children living with HIV (CLWH) who were switching to second-line antiretroviral therapy (ART). Methods We conducted a cross-sectional study among CLWH as a sub-study of the CHAPAS-4 trial. Total body less head (TBLH) BMD and lumbar spine (LS) BMD were determined by DXA while the sound of speed (SOS), broad band ultrasound attenuation (BUA) and bone quality index (BQI) were determined by QUS. We evaluated the correlation between the DXA and QUS measurements using spearman correlation coefficient. Results A total of 167 children were enrolled; the median age was 9.4 (interquartile range = 6.0–12.0) years. Eighty-five (50.9%) were male. The median weight- for- age Z- score (IQR) was − 1.29(-2.16, -0.49) and height for age Z-score was − 1.03(-1.56, 0.01). SOS was weakly correlated with TBLH BMD R  = 0.35, P  < 0.001), lumbar spine bone apparent density (LSBMAD) ( R  = 0.19, P  = 0.01) and LS bone mineral content (BMC) ( R  = 0.31, P  < 0.001). BUA was moderately correlated with TBLH BMD ( R  = 0.50, P  < 0.001), BMC ( R  = 0.47, P  = 0.001), and LS BMC ( R  = 0.43, P  < 0.001) but weakly correlated with LSBMAD ( R  = 0.28, P  < 0.001). BQI was moderately correlated with TBLH BMC ( R  = 0.46, P  < 0.001), TBLH BMD ( R  = 0.46, P  < 0.001) and LSBMC ( R  = 0.41, P  < 0.001). There was weak correlation between LSBMAD and BUA ( R  = 0.28, P  < 0.001) BQI ( R  = 0.29, P  < 0.001). QUS Z-score was weakly correlated with TBLH BMD and ( R  = 0.30, P  < 0.01) and no correlation with LSBMAD ( R  = 0.07, P  = 0.35). Conclusion In CLWH, there was moderate correlation observed for TBLH measurements when comparing DXA to QUS, and weak correlation was found between LSBMAD and QUS measurements. There was a moderate correlation detected between the LSBMC and QUS.QUS may not be an appropriate substitute for DXA scan.

Objective To identify the correlates of early breastfeeding (BF) cessation and breastmilk expression (BE) among mothers 12 months after childbirth. Methods We used a case-control study design to compare characteristics between mothers who stopped BF and expressed breastmilk 12 months after childbirth in Uganda. BF practices were determined in 12-month follow-up interviews using an adapted World Health Organization infant feeding questionnaire. Univariate and bivariate logistic regression models identified correlates of early BF cessation and BE as distinct but related outcomes. Results The odds of early BF cessation were higher among mothers who expressed breastmilk irrespective of maternal age (adjusted odds ratio: 2.82; 95% confidence interval: 1.39, 5.68). Mothers who stopped BF and did not express breastmilk were more likely to be older than those who continued BF and did not express breastmilk during the first 12 postpartum months. Conclusion Mothers living with human immunodeficiency virus infection have disproportionately high odds of early BF cessation that may contribute to disparities in child health outcomes. Promotion of safe BF practices coupled with family and social support could be a viable preventive strategy for attenuating such disparities, especially among young mothers at risk of early BF cessation.

Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. www.controlled-trials.com ISRCTN13968779

Introduction Viral suppression is a critical component for preventing mother-to-child transmission of HIV(MTCT). Mothers’ perceptions of viral load suppression is crucial in the attainment of successful outcomes in preventing mother to child transmission of HIV. We therefore aimed to explore the experiences and perceptions of women on viral suppression. Methods This was a qualitative sub-study embedded in a cluster-randomized trial (NCT04122144) designed to improve viral load outcomes among pregnant and breastfeeding mothers living with HIV in four level III/IV health facilities in South-western Uganda. Thirty-two in-depth interviews were conducted with pregnant and breastfeeding women with HIV from 1st March 2020 to 30th September 2020 to explore their understanding and interpretation of viral suppression. Interviews were audio-recorded, transcribed, and coded in Dedoose software for analysis. Results A total of 32 Women living with HIV were enrolled in this qualitative study. WLHIV explained viral suppression in the context of attaining good health and having HIV-free babies. Adherence to ART was presented as a key avenue to viral suppression. The level of engagement with providers was presented as a key attribute of attaining viral suppression. The participants narrated their experiences with viral load testing within the routine services. However, they revealed experiencing some proximate barriers to suppression including anticipated stigma, challenges with non-disclosure of HIV status, pregnancy distress, and distance to the health facility. Conclusion The understanding and interpretation of viral suppression among pregnant and breastfeeding mothers living with HIV provides a basis for adopting behaviors leading to prevention of vertical transmission of HIV. Health care workers can support women by providing clear and culturally appropriate education about viral suppression, adherence strategies and creating a supportive and non-judgmental environment.

Research is being carried out to develop and test new potentially more effective tuberculosis vaccines. Among the vaccines being developed are those that target adolescents. This study explored the stakeholders' perceptions about adolescent participation in a hypothetical tuberculosis vaccine trial in Ugandan adolescents. Focus group discussions with adolescents, parents of infants and adolescents, and key informant interviews with community leaders and traditional healers were conducted. The majority of the respondents expressed potential willingness to allow their children participate in a tuberculosis vaccine trial. Main motivations for potential participation would be being able to learn about health-related issues. Hesitations included the notion that trial participation would distract the youths from their studies, fear of possible side effects of an investigational product, and potential for being sexually exploited by researchers. In addition, bad experiences from participation in previous research and doubts about the importance of research were mentioned. Suggested ways to motivate participation included: improved clarity on study purpose, risks, benefits and better scheduling of study procedures to minimize disruption to participants' academic schedules. Findings from this study suggest that the community is open to potential participation of adolescents in a tuberculosis vaccine trial. However, there is a need to communicate more effectively with the community about the purpose of the trial and its effects, including safety data, in a low-literacy, readily understood format. This raises a challenge to researchers, who cannot know all the potential effects of a trial product before it is tested.

[This corrects the article DOI: 10.1371/journal.pone.0288877.].

[This corrects the article DOI: 10.1371/journal.pone.0288877.].