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Sustainable birth defects surveillance systems provide countries with estimates of the prevalence of birth defects to guide prevention, care activities, and evaluate interventions. We used free and open-source software (Open Data Kit) to implement an electronic system to collect data for a hospital-based birth defects surveillance system at four major hospitals in Kampala, Uganda. We describe the establishment, successes, challenges, and lessons learned from using mobile tablets to capture data and photographs. After intensive training, surveillance midwives collected data using Android tablets with inbuilt logic checks; another surveillance midwife checked the quality of the data in real-time before data were securely uploaded onto a local server. Paper forms were used when needed as a backup for the electronic system. We experienced several challenges implementing the surveillance system, including forgotten passwords, unstable network, reduced tablet speed and freezing, loss of touch-screen sensitivity, decreased battery strength, and repetitive extensive retraining. We addressed these challenges by backing up and removing all photos from the tablet, uninstalling irrelevant applications to the study to increase storage space and speed, and monitoring and updating the system based mainly on feedback from the midwives. From August 2015 to December 2018, surveillance midwives documented information on 110,752 births at the participating hospitals. Of these, 110,573 (99.8%) were directly entered into the electronic data system and 179 (0.2%) were captured on paper forms. The use of mobile tablets for real-time data collection was successful in a hospital-based birth defects surveillance system in a resource-limited setting. Extensive training and follow-up can overcome challenges and are key to preparing staff for a successful data collection system.

Introduction:Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called “Friends for Life Circles” (FLCs) versus the standard of care (SOC).Methods:Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm.Results:There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 – 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum.Conclusions:Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).

Contains fulltext : 249121.pdf (Publisher’s version ) (Open Access) BACKGROUND: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen. METHODS: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment. RESULTS: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups). CONCLUSIONS: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.).

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda.Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda’s National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify.Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4).Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens.

Pulmonary cryptococcosis is rare in immunocompetent individuals. Limited data exist regarding its occurrence in children, especially in developing countries. This case report describes an 8-year-old HIV-negative child with pulmonary cryptococco- sis, previously diagnosed and treated for tuberculosis twice without improvement. Fine needle aspiration biopsy confirmed the diagnosis of pulmonary cryptococcosis and serum cryptococcal antigen test was positive. The child improved on am- photericin and fluconazole treatment. Despite the limited diagnostic capacity in many resource-constrained settings like Uganda, this case report highlights the need to investigate other causes of pneumonia in immunocompetent children that are not improving on conventional antimicrobial treatments. Keywords: Pulmonary cryptococcosis; immunocompetent; children; Uganda.

Background:Micronutrient deficiencies due to malabsorption, gut infections, and altered gut barrier function are common in children living with HIV (CLHIV) and may worsen with severe acute malnutrition (SAM).Methods:This secondary analysis of IMPAACT P1092, a Phase IV, multicenter, open label, non-randomized study of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) pharmacokinetics, safety, and tolerability enrolled SAM and non-SAM CLHIV age 6 to ResultsFifty-two participants, 25 SAM and 27 non-SAM, of median (Q1,Q3) age 19 (13,25) and 18 (12,25) months respectively, were enrolled. Zinc deficiency was present at entry in 2/27 (8%) from the SAM cohort. Mean (SD) baseline zinc levels for the SAM and non-SAM cohort [52.2(15.3), 54.7(12.2) µg/dL] and selenium [92.9(25.0), 84.3(29.2) µg/L] were similar, and there was no difference in change from study entry to week 48 for both: mean (95% CI) difference SAM minus non-SAM of -0.3 (-11.2,10.5) µg/dL and -5.1 (-20.1,9.8) µg/L for zinc and selenium respectively. Mean (SD) baseline total protein levels [75.2(13.2), 77.3(9.4) g/L] and mean change from entry to 48 weeks were similar between cohorts (mean difference (95% CI) (4.6 (-2.4,11.6). The SAM cohort had significantly lower serum albumin levels at entry compared to the non-SAM cohort (mean difference (95% CI) 6.2 (-10.1, -2.4) g/L) and levels were similar after 48 weeks (mean difference (95% CI) 0.4 (-2.2, 2.9) g/L). Mean increase in albumin at 48 weeks was greater in the SAM cohort (mean difference (95% CI) 6.3 (1.9, 10.7) g/L). ConclusionsThese children who were on highly active combination antiretroviral therapy and had malnutrition showed normal levels of selenium and zinc after 10-18 days of nutritional rehabilitation. Entry albumin levels were lower in SAM compared to non-SAM, with normalization to non-SAM levels by 48 weeks. Total protein levels were similar at entry and week 48.Trial RegistrationThe study was registered with ClinicalTrials.gov Identifier NCT01818258 26/03/2013

Women who are pregnant or who could become pregnant experience delayed access to or underinformed use of important new antiretroviral (ARV) drugs because of traditional drug development processes that ostensibly aim to reduce potential harm but effectively fail to ensure that timely information about safe and effective use in pregnancy is available.The World Health Organization and International Maternal, Pediatric, Adolescent Antiretroviral Clinical Trials Network convened a year-long workshop on "Approaches to Enhance and Accelerate Study of New Drugs for HIV and Associated Infections in Pregnant Women." Workshop participants were tasked with defining key principles and optimal approaches to including pregnant women in pre- and post-licensure trials in order to accelerate the availability of pharmacokinetic and safety data for new ARV agents in pregnancy. ARV efficacy in pregnancy and ARV efficacy for prevention of vertical transmission can be extrapolated from proof of efficacy in non-pregnant adults, provided that drug levels in pregnancy are similar. However, short-term safety and pharmacokinetics must be studied directly in pregnant women and should be conducted and included in initial licensure for all new ARVs. Accelerating the timeline for completion of pre-clinical studies is essential for pregnancy short-term safety and pharmacokinetic studies to be safely completed by the time a drug is licensed. Composite key pregnancy, birth and neonatal outcomes are critical for drugs expected to have broad use, and studies should be initiated at or soon after drug licensure. Teratogenicity risk cannot be feasibly assessed before drug licensure and will depend on robust post-marketing surveillance systems. With some modifications, these principles will apply to ARVs used for prevention, two-drug regimens, long-acting ARVs and ARVs administered through novel delivery systems.Implementation of the proposed principles and framework will enhance and accelerate the study of new ARVs in pregnancy, resulting in more timely, equitable and informed access to new ARVs for pregnant women.

BackgroundSepsis severity scores are used in clinical practice and trials to define risk groups. There are limited data to derive hospital-based sepsis severity scores for neonates and young infants in high-burden low- and middle-income country (LMIC) settings where trials are urgently required. We aimed to create linked sepsis severity and recovery scores applicable to hospitalized neonates and young infants in LMIC which could be used to inform antibiotic trials.Methods & FindingsA prospective observational cohort study was conducted across 19 hospitals in 11 countries in sub-Saharan Africa, Asia, Latin America and Europe. Infants aged 3204 infants were enrolled between 2018-2020. Median age was 5 days (IQR 2-15), 90.4% (n=2,895) were A related NeoSep Recovery Score based on evolving post-baseline clinical signs and supportive care discriminated well between infants who died or survived the following day or subsequent few days. The area under the ROC curve for score on day 2 and death in the following 5 days was 0.82 (95%CI 0.78-0.85) and 0.85 (95%CI 0.78-0.93) in the derivation and validation data, respectively.ConclusionThe baseline NeoSep Severity Score predicted 28-day mortality and could identify infants with high risk of mortality for inclusion in hospital-based sepsis trials. The NeoSep Recovery Score predicts day-by-day inpatient mortality and could, with further validation, help to identify poor response to antibiotics.Author SummaryWhy was this study done?➣Evidence to guide hospital-based antibiotic treatment of sepsis in neonates and young infants is scarce, and clinical trials are particularly urgent in low- and middle-income (LMIC) settings where antimicrobial resistance threatens to undermine existing guidelines➣There is limited data to inform the design of antibiotic trials in LMIC settings, particularly to define risk stratification and inclusion and escalation criteria in hospitalised neonates and young infantsWhat did the researchers do and find?➣To our knowledge this is the first global, prospective, hospital-based observational study of clinically diagnosed neonatal sepsis across 4 continents including LMIC settings, with extensive daily data collection on clinical status, antibiotic use and outcomes.➣There was a high mortality among infants with sepsis in LMIC hospital settings. 4 non-modifiable and 6 modifiable factors predicted mortality and were included in a NeoSep Severity score which defines patterns of mortality risk at baseline➣A NeoSep Recovery Score including the same modifiable factors (with the addition of cyanosis) predicted mortality on the following day during the course of treatment.What do these findings mean?➣The NeoSep Severity Score and NeoSep Recovery score are now informing inclusion and escalation criteria in the NeoSep1 antibiotic trial (ISRCTN48721236) which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis➣The NeoSep Severity Score could be used to predict mortality at baseline in future studies of targeting resources in routine care. With further validation, the NeoSep Recovery Score could potentially be used to identify poor response to empiric antibiotic treatment

Background Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. Methods Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20–34 years. Results A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06–1.23), low birth weight (aOR: 1.46; CI 1.34–1.59), and early neonatal deaths (aOR: 1.58; CI 1.23–2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02–1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12–9.13) compared to mothers 20–34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7–14.3) was statistically significant when compared to mothers 20–34 years (1.6 per 10,000 births; 95% CI 0.9–2.6). Conclusions This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population., Plain English Summary Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes. Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years). In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Item does not contain fulltext BACKGROUND: Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS: We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. RESULTS: From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). CONCLUSIONS: In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).

Background There is a growing number of adolescents and young adults living with HIV (YPLHIV) who require the transfer of care from pediatric/ adolescent clinics to adult Antiretroviral therapy (ART) clinics. A successful transition is critical for optimum health outcomes, yet facilities may lack infrastructure, human resources (with appropriate knowledge and skills), and a supportive environment, as only 3% of clinics in Uganda caring for YPLHIV have a process for supporting this critical transition from pediatric to adult care, and, facilitators and barriers of a successful transition are not well documented. The purpose of this study was to explore the facilitators and barriers of transitioning among adolescents from adolescent clinics to adult ART clinics. Method Eighteen focus group discussions were held in nine health facilities with 174 adolescents and YPLHIV to assess barriers and facilitators regarding transitioning to adult clinics. The focus group discussions were audio-recorded and transcribed. The Silences Framework using a thematic approach guided the analysis. Results The key emerging issues were: Unfriendly adults in adult clinics, Care provided in the adolescent clinics, fear of stigma from health care providers, Congestion and long waiting time, fear to lose friends were barriers to transitioning. Transitioning preparation is key to a successful transition, moving as a cohort facilitates transition, and care in adult clinics offers new opportunities, could facilitate readiness and transition. Conclusion YPLHIV expressed fear to transition to adult clinics mainly because of the perceived better care provided in the adolescent clinic, thus constituting a barrier to smooth transition A range of individual, social and health system and services-related factors hindered transitioning. The expectation of transitioning as a group, assurance of similar care as in the adolescent clinic, and guarantees of confidentiality, privacy, and autonomy in decision-making for care was perceived as facilitators. Understanding barriers and facilitators can enable the Ministry of Health to improve the quality of life of YPLHIV through linkage to care, adherence, retention, and viral suppression. There is a need to better planning and preparation for clinical providers and YPLHIV with a focus on age-appropriate and individualized case management transition as well as focus on improving both clinical and psychosocial support throughout the process.

Background: HIV disclosure is a critical component of HIV prevention and treatment programs. Community Health Workers (CHW) play an important role in HIV disclosure counseling among HIV-affected heterosexual partners. However, time to disclosure attributed to the use of CHW in the disclosure process remains undocumented. This study assessed the effect of CHW-facilitated counseling on time to partner disclosure among Adults living with HIV (ALHIV) in the greater Luwero region, Uganda Methods: We conducted a two-arm cluster, non-randomized controlled trial. HIV care facilities in the greater Luwero region were allocated to either the intervention or control arm. Eligible participants were ALHIV in heterosexual partnerships who had never disclosed to their current partners. In the control arm, participants received routine regular facility-based counseling. In the intervention arm, alongside usual care, participants received CHW-facilitated disclosure counseling. Data were collected at baseline, 3 and 6 months with the primary outcome of disclosure. Survival analysis with proportional hazard ratios was used to determine the time to disclosure in both arms. Results: A total of 245 participants were enrolled, of whom complete data were available for 230 (93.9%). Of these, 112 (48.7%) were in the intervention arm and 118 (51.3%) were in the control arm. Mean ± SD age was 31±8 years with a range of 18 to 55 years. More participants were females 176 (76.5%). The cumulative incidence of disclosure was higher in the intervention arm 8.76 [95% CI: 7.20-10.67] per 1,000 person-time versus 5.15 [95%CI: 4.85-6.48] per 1,000 person-time in the control arm, log-rank test, X 2 = 12.93, P6 months, aHR = 1.19 [95% CI: 1.16-1.22] predicted disclosure. Prior disclosure to a relative, aHR = 0.55 [95% CI: 0.39-0.78] and having >1 sexual partner in the past 3 months, aHR = 0.74 [95% CI: 0.60-0.92] predicted non-disclosure Conclusion: CHW-led counseling increased the rate of partner HIV disclosure among ALHIV in heterosexual partnerships. Therefore, CHW-facilitated counseling may be used to quicken disclosure, reduce stigma and improve HIV treatment outcomes among ALHIV with disclosure difficulties.

Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and

Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to

Background Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). Methods Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. Results The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982). Conclusion Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Background The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. Methods Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs). Results A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]). Conclusion The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated.

BackgroundThere are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV.MethodsThe PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly.ResultsOf 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ).ConclusionWith HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.

Background: We evaluated the efficacy of a community health worker (CHW)–led intervention in supporting disclosure among adults living with HIV in heterosexual relationships. Methods: We conducted a quasi-experimental study with 2 arms allocated by geographically determined clusters and adjusted for between-group differences among adults living with HIV in the greater Luwero region of Uganda who had never disclosed their status to their current primary sexual partners. Clusters were allocated to either a CHW-led intervention or a control arm. In both arms, participants were consecutively recruited. As opposed to receiving routine care for the control arm, participants in the intervention arm received additional CHW disclosure support. The overall follow-up was 6 months, and the primary outcome was disclosure to the sexual partner. Data were analyzed using a clustered modified Poisson regression model with robust standard errors to determine independent factors associated with disclosure. Results: Of the 245 participants who enrolled, 230 (93.9%) completed the study, and 112 (48.7%) of those were in the intervention arm. The median age was 30 (interquartile range=25–37) years, the majority were women (76.5%), and most (80%) did not know their partners’ HIV status at study entry. At the end of follow-up, the overall disclosure prevalence was 74.4% (95% confidence interval [CI]=68.2, 79.9) and participants in the intervention arm were 51% more likely to disclose compared to those in the control (adjusted relative ratio [aRR]=1.51; 95% CI=1.28, 1.77). Men were 24% (aRR=1.24; 95% CI=1.07, 1.44) more likely to disclose compared to women, and membership in an HIV/AIDS association increased disclosure by 18% (aRR=1.18; 95% CI=1.01, 1.39). Conclusion: CHW support improved disclosure among adults living with HIV in heterosexual relationships when compared to routine care. Therefore, CHW-led mechanisms may be utilized in increasing disclosure among adults living with HIV in heterosexual relationships in rural settings.

BackgroundCOVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown which restricted individuals movements in Uganda limited access to services. MethodsAn observational study, using routinely collected data from Electronic Medical Records was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019 - March 2020), during (April 2020 - June 2020) and after the national lockdown (July 2020 - December 2020). ResultsBetween 1st July 2019 and 31st December 2020 there were 14,401 antenatal clinic attendances, 33,499 deliveries, 111,658 childhood service attendances and 57,174 for sexual health. All antenatal and vaccination services ceased in lockdown for four weeks. During the three-month lockdown, the number of antenatal attendances significantly decreased, and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined whilst neonatal death rate rose (from 39-49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown. ConclusionThe Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications, and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health. O_TEXTBOXKEY QUESTIONS What is already known?O_LIThe response to COVID-19 has been shown to have indirectly impacted on maternal, child, neonatal, sexual, and reproductive health. C_LIO_LIThis is largely related to access to services and fear of contracting COVID-19 in outpatient departments. C_LIO_LIThere has been very little data published on the health impacts of the COVID-19 response in Uganda. C_LI What are the new findings?O_LIAntenatal attendances decreased dramatically in April, followed by increased numbers low-birthweight infants and neonatal deaths. C_LIO_LINewborn immunisations against polio, tetanus, diphtheria, hepatitis B, haemophilus influenzae, rotavirus and pneumococcus decreased significantly. C_LIO_LISexual, and reproductive health services were reduced in number. C_LI What do the new findings imply?O_LIAlthough Uganda has been less affected directly by COVID-19 infections in the first wave, the indirect impacts are far-reaching and will have future influences on population health. C_LIO_LIThere is a degree of resilience within the healthcare service, but many services were adversely affected by the lockdown leading to poorer pregnancy and neonatal outcomes. C_LIO_LIAntenatal and vaccination services are of particular importance in ensuring the safety of mother and child and must be prioritised in the responses to future pandemics. C_LI C_TEXTBOX

ObjectiveTo gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).DesignA web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.Setting39 NNUs from 12 countries.PatientsAny neonate admitted to one of the participating NNUs.InterventionsThis was an observational cohort study.ResultsThe number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions ConclusionAMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV.Th BONE: CARE study was a prospective cohort study that recruited women aged 18-35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD.Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3·406% [95% CI -3·969 to -2·844] vs -1·111% [-1·929 to -0·293]; p0·0001), total hip (-3·856% [-4·449 to -3·264] vs -1·714% [-2·479 to -0·949]; p=0·0002), and femoral neck (-4·422% [-5·078 to -3·766] vs -1·999% [-3·022 to -0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (-0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p0·0001) than TDF alone (lumbar spine -2·677% [95% CI -3·743 to -1·611]; p0·0001; total hip -2·518% [-3·575 to -1·461]; p0·0001; and femoral neck -2·907 [-4·132 to -1·683]; p0·0001) or than controls (lumbar spine -4·970% [-6·391 to -3·549]; p0·0001; total hip -4·151% [-5·579 to -2·724]; p0.0001; and femoral neck -4·773% [-6·424 to -3·122]; p0·0001) INTERPRETATION: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV.National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Background HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART. Methods We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load Results We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03). Conclusions We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.

Background Transition readiness refers to a client who knows about his/her illness and oriented towards future goals and hopes, shows skills needed to negotiate healthcare, and can assume responsibility for his/ her treatment, and participate in decision-making that ensures uninterrupted care during and after the care transition to adult HIV care. There is a paucity of research on effective transition strategies. This study explored factors associated with adolescent readiness for the transition into adult care in Uganda. Methods A cross-sectional study was conducted among 786 adolescents, and young people living with HIV randomly selected from 9 antiretroviral therapy clinics, utilizing a structured questionnaire. The readiness level was determined using a pre-existing scale from the Ministry of Health, and adolescents were categorized as ready or not ready for the transition. Bivariate and multivariate analyses were conducted. Results A total of 786 adolescents were included in this study. The mean age of participants was 17.48 years (SD = 4). The majority of the participants, 484 (61.6%), were females. Most of the participants, 363 (46.2%), had no education. The majority of the participants, 549 (69.8%), were on first-line treatment. Multivariate logistic regression analysis found that readiness to transition into adult care remained significantly associated with having acquired a tertiary education (AOR 4.535, 95% CI 1.243–16.546, P = 0.022), trusting peer educators for HIV treatment (AOR 16.222, 95% CI 1.835–143.412, P = 0.012), having received counselling on transition to adult services (AOR 2.349, 95% CI 1.004–5.495, P = 0.049), having visited an adult clinic to prepare for transition (AOR 6.616, 95% CI 2.435–17.987, P = < 0.001) and being satisfied with the transition process in general (AOR 0.213, 95% CI 0.069–0.658, P = 0.007). Conclusion The perceived readiness to transition care among young adults was low. A series of individual, social and health system and services factors may determine successful transition readiness among adolescents in Uganda. Transition readiness may be enhanced by strengthening the implementation of age-appropriate and individualized case management transition at all sites while creating supportive family, peer, and healthcare environments.

Background Whereas many adolescents and young people with HIV require the transfer of care from paediatric/adolescent clinics to adult ART clinics, this transition is beset with a multitude of factors that have the potential to hinder or facilitate the process, thereby raising ethical challenges of the transition process. Decisions made regarding therapy, such as when and how to transition to adult HIV care, should consider ethical benefits and risks. Understanding and addressing ethical challenges in the healthcare transition could ensure a smooth and successful transition. The purpose of this study was to analyze the ethical challenges of transitioning HIV care for adolescents into adult HIV clinics. Methods Data presented were derived from 191 adolescents attending nine different health facilities in Uganda, who constituted 18 focus group discussions. In the discussions, facilitators and barriers regarding adolescents transitioning to adult HIV clinics were explored. Guided by the Silences Framework for data interpretation, thematic data analysis was used to analyze the data. The principles of bioethics and the four-boxes ethics framework for clinical care (patient autonomy, medical indications, the context of care, and quality of life) were used to analyze the ethical issues surrounding the transition from adolescent to adult HIV care. Results The key emerging ethical issues were: reduced patient autonomy; increased risk of harm from stigma and loss of privacy and confidentiality; unfriendly adult clinics induce disengagement and disruption of the care continuum; patient preference to transition as a cohort, and contextual factors are critical to a successful transition. Conclusion The priority outcomes of the healthcare transition for adolescents should address ethical challenges of the healthcare transition such as loss of autonomy, stigma, loss of privacy, and discontinuity of care to ensure retention in HIV care, facilitate long-term self-care, offer ongoing all-inclusive healthcare, promote adolescent health and wellbeing and foster trust in the healthcare system. Identifying and addressing the ethical issues related to what hinders or facilitates successful transitions with targeted interventions for the transition process may ensure adolescents and young people with HIV infection remain healthy across the healthcare transition.

BackgroundThis study set out to determine the prevalence of low bone mass following long-term exposure to antiretroviral therapy in Ugandan people living with HIV.MethodsA cross-sectional study was conducted among 199 people living with HIV that had been on anti-retroviral therapy for at least 10 years. All participants had dual X-ray absorptiometry to determine their bone mineral density. The data collected included antiretroviral drug history and behavioral risk data Descriptive statistics were used to summarize the data. Inferential statistics were analyzed using multilevel binomial longitudinal Markov chain Monte Carlo mixed multivariate regression modelling using therstanarmpackage.ResultsOne hundred ninety nine adults were enrolled with equal representation of males and females. The mean age was 39.5 (SD 8.5) years. Mean durations on anti-retroviral treatment was 12.1 (SD 1.44) years, CD4 cell count was 563.9 cells/mm3. 178 (89.5%) had viral suppression with ConclusionThese results provide additional evidence that patients on long term ART achieve bone mass stabilization. Maintaining adequate body weight is important in maintaining good bone health in people on antiretroviral therapy.

Objectives To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). Methods Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. Results Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). Conclusions Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Background Many adolescents and young people with HIV require the transfer of care from paediatric/ adolescent clinics to adult ART clinics. Transition is beset with factors that hinder or facilitate the process, thereby raising the transition process’s ethical challenges. Decisions made regarding therapy, such as when and how to transition to adult HIV care, should consider ethical benefits and risks. Understanding and addressing ethical challenges in the healthcare transition could ensure a successful transition. The purpose of this study was to analyse the ethical challenges of transitioning HIV care for adolescents into adult HIV clinics. Method We conducted 18 focus group discussions among 191 adolescents attending nine different health facilities in Uganda. We explored facilitators and barriers regarding adolescents transitioning to adult HIV clinics. Thematic data analysis was used to analyze the data. The Silences Framework guided data analysis and interpretation. The principles of Bioethics and the four-boxes ethics framework for clinical care (Patient autonomy, Medical indications, Context of Care and Quality of life) were used to analyze the ethical issues surrounding the transition to adult HIV care. Results The key emerging ethical issues were: reduced patient autonomy; increased risk of harm from stigma and loss of privacy and confidentiality; unfriendly adult clinics induce disengagement and disruption of the care continuum; patient preference to transition as a cohort and contextual factors are critical to a successful transition. Conclusion The priority outcomes of the healthcare transition for adolescents should address ethical challenges of the healthcare transition to ensure retention in HIV care, facilitate long-term self-care, provide ongoing holistic healthcare and support to promote health and wellbeing and build trust in the healthcare system. Identifying what facilitates successful transitions and the gaps that interventions can target may ensure adolescents and young people with HIV infectionremain healthy across the healthcare transition.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

Most studies evaluating BMD in human immunodeficiency virus (HIV)‐infected populations have focused on antiretroviral therapy (ART)‐experienced patients. In this study, the association between HIV‐1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV‐1–infected women in a resource‐limited setting was assessed before long‐term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non‐Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV‐1 status and DMPA use: (i) HIV‐1–infected current DMPA users, (ii) HIV‐1–infected previous DMPA users, (iii) HIV‐1–infected nonhormonal‐contraceptive users, and (iv) HIV‐uninfected nonhormonal‐contraceptive users. All HIV‐1–infected women reported being ART‐naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV‐1 and/or DMPA and BMD Z‐scores. Baseline data were analyzed for 452 HIV‐1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV‐1–uninfected nonhormonal‐contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12‐48]. A higher proportion of HIV‐1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z‐score ≤−2 at any of the three sites) compared with age‐matched HIV‐1–uninfected women (2.9%). HIV‐1 infection and DMPA use were independently associated with significantly lower mean BMD Z‐scores at all sites, with the greatest difference being among HIV‐1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non‐Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV‐1–infected women in resource‐limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and older mothers (age 20-34 years) in four urban hospitals.Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% Confidence Intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to older mothers.Results: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI: 1.06-1.23), low birth weight (aOR: 1.46; CI: 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI: 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI: 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI: 1.12-9.13) compared to older mothers. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI: 3.7-14.3) was statistically significant when compared to older mothers (1.6 per 10,000 births; 95% CI: 0.9-2.6).Conclusions: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to older mothers, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Objective To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. Design Longitudinal cohort study. Methods In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. Results Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/ml was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. Conclusions As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viraemia who remain at low risk of disease progression.

Since 2012, PMTCT Option B+ has been recommended by the World Health Organization to reduce vertical transmission but numerous adherence challenges remain. We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention. Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model. In line with the model, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behaviour of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere.

Caregiver's and child's self-reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6-10 years old HIV-infected, HIV-exposed uninfected, and HIV-unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child- and caregiver-reported psychosocial stress were dose-dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1-14.8, effect size [ES] = 0.46-0.83). Lower allostasis was dose-dependently associated with higher QOL (b = 6.1-9.7, ES = 0.34-0.54). Given low caregiver acute stress, QOL for HIV-infected was similar to HIV-uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = -7.8, 95% CI: -12.8, -2.8; ES = -0.73) was evident for HIV-infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.

Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037.Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR.High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa.The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

BackgroundMortality among children under 5 years of age admitted to malnutrition units in sub-Saharan Africa remains high. The burden of HIV infection, a major risk factor for mortality among patients with severe acute malnutrition (SAM), has reduced due to concerted prevention and treatment strategies. None the less, anecdotal reports from the malnutrition unit at Uganda’s National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. Uganda has recently adopted the revised World Health Organization (WHO) treatment guidelines for SAM to improve outcomes. The mortality among children with SAM in routine care has not been recently elucidated. We report the magnitude and factors associated with mortality among children under 5 years of age admitted to the NRH for routine care of SAM.MethodsThis was a cohort study of all severely malnourished children admitted to the NRH between June and October 2017. The primary outcome was two-week mortality. Mortality was calculated using simple proportions and Cox regression analysis was used to determine factors associated with time to mortality. Data was entered into Epidata and analysed using Stata v14.ResultsTwo-hundred-sixty (98.5%) children: 59.6% male; mean age 14.4 (SD 9.4) months, completed two weeks of follow-up. Of these, 25.2% (95% CI 19.9–30.4%) died. In-hospital mortality was 20.7% (95% CI15.9–25.6%). The prevalence of HIV infection was 12.2%. Factors associated with mortality included: positive HIV status (AHR 2.2, (95% CI; 1.2–4.2),p = 0.014), bacteraemia (AHR 9 (95% CI 3.4–23.0),p p = 0.001).ConclusionsA 25% mortality among children with severe malnutrition remains unacceptably high despite significant reduction in HIV prevalence. Children with SAM who are HIV infected, have eGFR below 60 mL/min/1.73m2or have bacteraemia, are more likely to die. Further studies to explore the relationship between eGFR and mortality among children with SAM are needed. Studies to establish efficacious antibiotics are urgently required to inform treatment guidelines for children with SAM.

BACKGROUND: The objective of this study was to evaluate the comparative effects of three breastfeeding promotion interventions on the duration of exclusive breastfeeding (EBF) and any breastfeeding (BF) among human immunodeficiency virus (HIV)-infected women in Uganda. METHODS: Between February 2012 and February 2013, 218 HIV-infected pregnant mothers were randomly assigned to (A) standard care (n=73), (B) enhanced family/peer support (n=72) or (C) enhanced nutrition education (n=73). RESULTS: The prevalence (%) of EBF/BF did not differ between intervention arms at the sixth (A, 85/92; B, 84/91; C, 87/89) and ninth (A, 17/91; B, 18/89; C, 16/87) postpartum month assessments (p>0.05). However, the risk of early BF cessation differed between intervention arms depending on the mother’s level of formal education (p=0.04). Among women with no formal education, the risk of early BF cessation was 88% (adjusted hazard ratio [aHR] 0.12 [95% confidence interval {CI} 0.05–0.30]) and 93% (aHR 0.07 [95% CI 0.03–0.18]) lower in arms B and C, respectively, than in arm A (p

The goal of this paper is to review the prevention of mother-to-child HIV transmission (PMTCT) research that informed World Health Organization (WHO) guidelines for PMTCT and describe the impact of worldwide scale-up of PMTCT programs and antiretroviral therapy (ART) coverage. The impact of these interventions on new pediatric infections and infected children’s morbidity and mortality in sub-Saharan Africa are reviewed. The IMPAACT PROMISE study demonstrated that triple therapy consisting of tenofovir (TDF), lamivudine (3TC), and lopinavir/ritonavir (LPVr) or zidovudine (AZT), 3TC, and LPVr initiated in the first trimester reduced vertical transmission at 2 weeks of age to 0.6% and 0.5%, respectively, supporting the current WHO Option B+ recommendation for PMTCT. However, increased adverse pregnancy outcomes in the AZT- and TDF-based triple therapy arms were reported when compared with the AZT prophylaxis arm (low birth weight [20.4% and 16.9% vs. 8.9%; p = 0.004] and premature deliveries [19.7% and 18.5% vs. 13.5%; p = 0.09], respectively). Implementation of Option B+ for PMTCT has led to significant reductions in vertical transmission rates, including elimination of new pediatric infections in some countries. The WHO declared elimination of mother-to-child HIV transmission (MTCT) in Cuba in 2015 and in Armenia, Belarus, and Thailand in 2016. Globally, new pediatric HIV infections have declined significantly since the introduction of effective antiretroviral regimens for PMTCT. Perinatal HIV prevention clinical trials conducted in sub-Saharan Africa informed WHO PMTCT guidelines which led to implementation of PMTCT programs worldwide, leading to a 47% reduction in new pediatric infections since 2009. Support from The United States President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund for AIDS, Tuberculosis and Malaria, and UN agencies has enabled scale-up of national PMTCT programs, and increased antiretroviral coverage (47% globally) for infected children has led to a decline in HIV/AIDS-related mortality in children. Implementation strategies that improve retention in care and adherence to ART in pregnant and breastfeeding HIV-infected women is critical to ensure that more countries achieve the elimination of MTCT (eMTCT) targets. Assessing the effectiveness of new antiretroviral drugs, including fixed-dose combinations and long-acting formulations, is key to improving ART adherence and reducing the emergence of viral resistance mutations. In addition, interventions to prevent HIV transmission in adolescents and young adults is critical for reducing new HIV infections worldwide. Innovative interventions to improve adherence to ART are required to further improve the survival of HIV-infected children and adolescents.

Objective: Option-B+ programs in Uganda have reported high levels of loss to follow up (LTFU) after cessation of breastfeeding, and this remains unknown beyond this period. In this study, we assessed the incidence and factors associated with LTFU two to four years after delivery among Option-B+ mothers. Study design: Retrospective cohort. Methods: We reviewed files of 452 mothers who enrolled on Option-B+ between January 1st, 2013 and December 31st, 2014 ​at Kisenyi Health Centre IV in Kampala district. We assessed factors associated with LTFU using Cox proportional hazards regression. We also explored the reasons for LTFU using three focus group discussions, five in-depth and three key informant interviews. Results: Of the 452 mothers, 131(29%) were LTFU after delivery. The incidence of LTFU after delivery was 17/1000 person months (95% CI, 14–30/1000) with a median follow up of 32 months. The risk of LTFU was higher among mothers who started ART on the day they tested HIV positive (aHR ​= ​1.66, 95% CI; 1.25–2.20, p-value< 0.001). Reasons for LFTU included transport costs, stigma, poor human resource policies and non-disclosure. Conclusion: LTFU after delivery among Option-B+ mothers is higher than the global target of 15%. ART initiation on the day a mother tests positive increases the risk of LTFU. The major reasons for LTFU were stigma and non-disclosure. To reduce the risk of LTFU, we recommend approaches that encourage disclosure to sexual partners and ongoing specific support to mothers who are initiated on ART-the day of positive test.

To examine quality of life (QOL) in perinatally HIV-infected (PHIV) or HIV-exposed uninfected (PHEU) vs. healthy HIV-unexposed uninfected (HUU) children during school-age/adolescence.PHIV infection was diagnosed via DNA PCR. Current HIV status was confirmed by HIV rapid diagnostic test. Three HIV groups were defined: PHIV, PHEU, and HUU. QOL was assessed with proxy and self-report versions of the PedsQL™ 4.0 instrument at 6-18 years of age. QOL scores ranged from zero (least QOL) to 100 (highest QOL) in the following dimensions: combined QOL inventory (CQOLI), multi-dimensional vigor (MDV), general wellbeing (GWB), present functioning, and general cognitive functioning (CF). Multivariable linear regression models estimated HIV-related percent differences (β) in QOL scores and 95% confidence intervals (CI).Compared to HUU CQOLI deficits ranged from 6.5 to 9.2% (95% CI -15.4, -1.6), GWB deficit ranged from 6.5 to 10.5% (95% CI -16.0, -1.3), MDV deficit ranged from 6.8 to 11.6% (95% CI -14.5, 0.9), and CF deficit ranged from 9.7 to 13.1% for PHIV children. QOL deficits of similar magnitude and direction in most domains were observed for PHIV compared to PHEU. However, self-reported indicators of GWB (β = -3.5; 95% CI -9.0, 2.0) and present functioning (β = 4.0; 95% CI -4.6, 12.5) were similar for PHIV compared to PHEU. QOL scores were generally similar for PHEU compared to HUU.PHEU and HUU had similar QOL profile but PHIV predicted sustained deficits in multiple QOL domains. PHIV and PHEU children were similar with respect to general wellbeing and present functioning. Psychosocial and scholastic interventions in combination with HIV care are likely to improve QOL in PHIV.

The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP.We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT.ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay.K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.

BackgroundIn 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do not have surveillance programs. This paper shares the results of a hospital-based birth defects surveillance program in Uganda which, can be adopted by similar resource-limited countries.MethodsAll informative births, including live births, stillbirths and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2017 were examined for birth defects. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes and entered in an electronic data collection tool. Identified birth defects were confirmed through bedside examination by a physician and review of photographs and a narrative description by a birth defects expert. Informative births (live, still and spontaneous abortions) with a confirmed birth defect were included in the numerator, while the total informative births (live, still and spontaneous abortions) were included in the denominator to estimate the prevalence of birth defects per 10,000 births.ResultsThe overall prevalence of birth defects was 66.2/10,000 births (95% CI 60.5–72.5). The most prevalent birth defects (per 10,000 births) were: Hypospadias, 23.4/10,000 (95% CI 18.9–28.9); Talipes equinovarus, 14.0/10,000 (95% CI 11.5–17.1) and Neural tube defects, 10.3/10,000 (95% CI 8.2–13.0). The least prevalent were: Microcephaly, 1.6/10,000 (95% CI 0.9–2.8); Microtia and Anotia, 1.6/10,000 (95% CI 0.9–2.8) and Imperforate anus, 2.0/10,000 (95% CI 1.2–3.4).ConclusionA hospital-based surveillance project with active case ascertainment can generate reliable epidemiologic data about birth defects prevalence and can inform prevention policies and service provision needs in low and middle-income countries.

Background: Mortality among children under five years of age admitted to malnutrition units in sub-Saharan Africa remains high. The burden of HIV infection, a major risk factor for mortality among patients with severe acute malnutrition (SAM), has reduced due to concerted prevention and treatment strategies. None the less, anecdotal reports from the malnutrition unit at Uganda’s National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. Uganda has recently adopted the revised World Health Organization (WHO) treatment guidelines for SAM to improve outcomes. The mortality among children with SAM in routine care has not been recently elucidated. We report the magnitude and factors associated with mortality among children under five years of age admitted to the NRH for routine care of SAM. Methods: This was a cohort study of all severely malnourished children admitted to the NRH between June and October 2017. The primary outcome was two-week mortality. Mortality was calculated using simple proportions and Cox regression analysis was used to determine factors associated with time to mortality. Data was entered into Epidata and analysed using Stata v14. Results: Two-hundred-sixty (98.5%) children: 59.6% male; mean age 14.4 (SD 9.4) months, completed two weeks of follow-up. Of these, 25.2 % (95% CI 19.9-30.4%) died. In-hospital mortality was 20.7% (95% CI 15.9-25.6%). The prevalence of HIV infection was 12.2%. Factors associated with mortality included: positive HIV status (AHR 2.2, (95% CI; 1.2-4.2), p=0.014), bacteraemia (AHR 9 (95% CI 3.4-23.0), p

Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support.Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status.As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (β = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (β = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (β = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%).Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting.Les attributs socio-affectifs des responsables d'enfants sont des déterminants majeurs du bien-être des enfants. Cette investigation menée auprès d'enfants ougandais vulnérables d’âge scolaire a estimé les relations entre le bien-être des enfants et l'anxiété, la dépression et le soutien social de leur responsable. MÉTHODES: Des enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à l’âge de 18 mois à l'aide du test de PCR de l’ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bien-être de l'enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l'aide de méthodes validées, adaptées à la culture et respectées et d'outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (β) et les intervalles de confiance (IC) à 95% correspondants pour le bien-être de l'enfant par rapport au statut psychosocial de leurs responsables. RÉSULTATS: Par incrément de tertile, l'anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (β = −1,3%/−2,6%; IC95%: −5,0%, −0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (β = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l'estime de soi/QV diminuait de 2,3% (β = −2,3%/−4,4%; IC95%: −7,2%, −1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (β = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (β = −5,2%/−6,8%; IC95%: −12,4%, −0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (β = 4,5%; IC95%: 1,9%, 7,1%).L'anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bien-être précaire chez les enfants d’âge scolaire et les adolescents. L'amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bien-être des enfants et des adolescents vulnérables dans cette région.

About 2.1 million adolescents aged 10-19years are living with HIV, 80% of them in sub-Saharan Africa. Early sexual activity remains an important risk factor for HIV transmission and potentially result in negative health consequences including onward transmission of sexually transmitted infections. Cross-sectional data of 580 adolescents living with HIV (ALHIV) aged 13-17years (317 girls and 263 boys) from Kenya and Uganda were analyzed to assess factors associated with risk to become sexually active. Factors associated with risk of sexual intercourse were identified using Kaplan-Meier survival curves and Cox regression with gender-stratified bi-and multivariable models. Slightly more females (22%) than males (20%) reported they have had sex. Multivariable models showed that being aware of one's own HIV infection, and receiving antiretroviral treatment were negatively associated with risk of becoming sexually active, while subjective norms conducive to sexuality, and girls' poor health experience increased the risk. In the final multi-variable models, schooling was protective for girls, but not for boys. Being more popular with the opposite sex was negatively associated with the outcome variable only for girls, but not for boys. This study expands the knowledge base on factors associated with onset of sexual activity among ALHIV, potentially informing positive prevention interventions. ResumenAlrededor de 2.1 millones de adolescentes de entre 10 y 19 anos viven con el VIH, el 80% de ellos residen en el africa subsahariana. La actividad sexual precoz sigue siendo un factor de riesgo importante para la transmision del VIH y puede tener consecuencias negativas para la salud, incluida la transmision de infecciones de transmision sexual. Los datos transversales de 580 adolescentes entre los 13-17 anos (317 ninas y 263 ninos) viviendo con el VIH y originarios de Kenia y Uganda fueron analizados para evaluar los factores asociados con el riesgo de volverse sexualmente activos. Los factores asociados con el riesgo de tener relaciones sexuales se identificaron usando las curvas de supervivencia de Kaplan-Meier y la regresion de Cox con modelos bi y multivariables estratificados por genero. Un poco mas de mujeres adolescentes (22%) que de hombres adolescentes (20%) informaron haber tenido relaciones sexuales. Los modelos multivariables mostraron que ser conscientes de la propia infeccion por VIH y recibir tratamiento antiretroviral se asociaron negativamente con el riesgo de volverse sexualmente activos, mientras que las normas subjetivas promoviendo la sexualidad y la mala salud experimentada por las mujeres adolescentes aumentaron el riesgo. En los modelos finales de variables multiples, la escolarizacion resulto ser un factor de proteccion para las mujeres, pero no para los hombres adolescentes. Ser mas popular con el sexo opuesto se asocio negativamente con la variable de resultado pero solo para las mujeres, no para los hombres adolescentes. Este estudio amplia la base de conocimientos sobre los factores asociados con el inicio de la actividad sexual en el VIH lo que podria contribuir a las intervenciones de prevencion positivas.

Background Preterm infants are at increased risk of infections including vaccine preventable diseases. Therefore, timely vaccination is crucial to ensure adequate disease protection. Information on whether preterm infants are vaccinated according to chronological age as recommended is limited in low-income countries. Objectives We evaluated the timeliness of vaccination and associated factors among preterm infants at Mulago hospital, Uganda. Methods We conducted a mixed methods study between July 2016 and April 2017. Vaccination dates of preterm infants aged 6–24 months were obtained from child health cards. Additional data were collected using a questionnaire. Five key informant interviews with health workers and two focus group discussions with caregivers were conducted. Cox regression analysis was used to identify factors associated with vaccination timeliness. Qualitative data was transcribed and analysed manually using content thematic approach. Results We enrolled 350 preterm infants, with a median age of 8.4 months (IQR 6.8–10.8). Less than half, 149/350 (42.6%) of infants received all vaccines within the recommended time range. Timely vaccination was highest for BCG (92%) and lowest for OPV (45.4%). Untimely vaccination was highest for vaccines administered at 6 weeks (DPT 1, PCV 1 and OPV 1) compared to other vaccines in the EPI schedule. Delivering from home or private clinics and vaccine stock-out were significantly associated with untimely BCG and OPV 0 vaccination. Low maternal education level and being very preterm were associated with untimely DPT 1 and DPT 3 receipt. Admission and long stay in the neonatal unit were associated with untimely DPT 1 receipt while extreme low birth weight was associated with untimely DPT 3 vaccination. Increasing parity was associated with untimely measles vaccination. Qualitative findings revealed that lack of knowledge and poor attitudes of health workers and caregivers, gaps in documentation of vaccination status and inadequate communication by health workers hindered timely vaccination. Conclusion More than half of preterm infants attending a specialised clinic at Mulago National Referral hospital in Uganda did not receive vaccines within the recommended time range. Specific strategies to improve vaccination timeliness in preterm infants are needed especially among the extremely low birth weight, very preterm and those with prolonged hospitalisation.