Prevalence of overweight and obesity among adolescents living with HIV after dolutegravir - based antiretroviral therapy start in Kampala, Uganda.

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the preferred first-line treatment for persons living with HIV (PLHIV) including children and adolescents in many low- and middle-income countries including Uganda. However, there are concerns about excessive weight gain associated with DTG especially in adults. There remains paucity of current information on weight-related outcomes among adolescents on DTG. We determined the prevalence of excessive weight gain and associated factors among adolescents living with HIV (ALHIV) receiving DTG-based ART in Kampala, Uganda. METHODS: Cross-sectional study involving ALHIV aged 10-19 years on DTG-based ART for at least one year were recruited from public health facilities in Kampala between February and May 2022. Excessive weight gain was defined as becoming overweight or obese per body mass index (BMI) norms while on DTG-based ART for at least one year. Demographic, clinical and laboratory data were collected using interviewer-administered questionnaires and data extracted from medical records. At enrolment, blood pressure and anthropometry were measured and blood was drawn for blood glucose and lipid profile. Data was summarised using descriptive statistics and logistic regression was performed to determine the associated factors. RESULTS: We enrolled 165 ALHIV with a median age of 14 years (IQR 12-16). Eighty (48.5%) were female. The median duration on ART and DTG was 8 years (IQR 7-11) and 2 years (IQR 1-3) respectively. At DTG initiation, the majority of participants (152/165, 92.1%) were ART-experienced, and had normal BMI (160/165, 97%). Overall, 12/165 (7.3%) adolescents (95% CI: 4.2-12.4) had excessive weight gain. No factors were significantly associated with excessive weight gain after DTG start in ALHIV. However, all ALHIV with excessive weight gain were females. CONCLUSION: Our study found a prevalence of 7.3% of overweight and obesity in ALHIV after initiating DTG. We did not find any factor significantly associated with excessive weight gain in ALHIV on DTG. Nonetheless, we recommend ongoing routine monitoring of anthropometry and metabolic markers in ALHIV as DTG use increases globally, to determine the exact magnitude of excessive weight gain and to identify those at risk of becoming overweight or obese while taking the medication.

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

It is not always Tuberculosis! A case of pulmonary cryptococcosis in an immunocompetent child in Uganda.

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 cryptococcosis, 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 amphotericin 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.

Leveraging investments in Ebola preparedness for COVID-19 in Sub-Saharan Africa.

The emergence of SARS-CoV-2 in China and transmission to more than 80 territories worldwide, including nine countries in Africa, presents a delicate situation for low-resource settings. Countries in Eastern and Central Africa have been on high alert since mid-2018 in anticipation of regional spread of the Ebola virus from the Democratic Republic of Congo. Significant investment has been made to support enhanced surveillance at point of entry and hospitals, infection control practices, clinical case management, and clinical research. With a new threat on the horizon, African countries have an opportunity to leverage the existing capacities for Ebola preparedness to brace for the imminent threat.

Vaccination timeliness and associated factors among preterm infants at a tertiary hospital in Uganda.

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.