A randomised feasibility trial of an intervention to support sharing of HIV status for 18-25-year olds living with perinatally acquired HIV compared with standard care: HIV Empowering Adults' Decisions to Share-UK/Uganda Project (HEADS-UP)

Abstract: Background: Young adults with perinatally acquired HIV (PAH) face several challenges, including adhering to antiretroviral therapy (ART), managing the risk of onward HIV transmission and maintaining positive well-being. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges by facilitating emotional and practical support. Rates of HIV status sharing are, however, low in this population. There are no existing interventions focused on sharing one's HIV status for young adults living with PAH. The HEADS-UP study is designed to develop and test the feasibility of an intervention to help the sharing of HIV status for young adults with PAH. Methods: The study is a 30-month multi-site randomised feasibility study across both a high-income/low-HIV prevalence country (UK) and a low-income/high-HIV prevalence country (Uganda). Phase 1 (12 months) will involve developing the intervention using qualitative interviews with 20 young people living with PAH (ten in the UK-18 to 29 years; ten in Uganda-18 to 25 years), 20 of their social network (friends, family, sexual partners as defined by the young person; ten in the UK, ten in Uganda) and ten professionals with experience working with young adults with PAH (five in the UK, five in Uganda). Phase 2 (18 months) involves conducting a randomised feasibility parallel group trial of the intervention alongside current standard of care condition in each country (main study) with 18- to 25-year olds with PAH. A sample size of 94 participants per condition (intervention or standard of care; 188 participants in total: 47 in each condition in each country) with data at both the baseline and 6-month follow-up time points, across UK and Ugandan sites will be recruited. Participants in the intervention condition will also complete measures immediately post-intervention. Face-to-face interviews will be conducted with ten participants in both countries immediately post-intervention and at 6-month follow-up (sub-study). Discussion: This study will be the first trial that we are aware of to address important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH. Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January, 2019. Study sponsor: Royal Holloway University of London. Sponsor contact: [email protected]. Date and version: April 2020. Protocol version 3.5

Outcomes of extremely low-birthweight neonates at a tertiary hospital in the Western Cape, South Africa : a retrospective cohort study

CITATION: Musiime, G. M. et al. 2021. Outcomes of extremely low-birthweight neonates at a tertiary hospital in the Western Cape, South Africa : a retrospective cohort study. South African Journal of Child Health, 15(3):170-175, doi:10.7196/SAJCH.2021.v15i3.01799.The original publication is available at http://www.sajch.org.zaBackground. Neonates of extremely low birthweight (ELBW; <1 000 g) have the highest neonatal mortality in South Africa (SA). Objective. To describe the morbidity and mortality of ELBW neonates treated at a tertiary hospital in SA. Methods. This was a retrospective cohort study including all live-born ELBW neonates treated at Tygerberg Hospital between 1 January and 31 December 2016. Data were extrapolated from a prospectively collected neonatal database and patient records. Multiple logistic regression and survival analysis were performed to identify risk factors of mortality. Results. The sample included 256 neonates. The following morbidities were recorded: respiratory distress syndrome (83.2%); bronchopulmonary dysplasia (8.2%); intraventricular haemorrhage (34.5%); periventricular leukomalacia (0.6%); necrotising enterocolitis (10.5%); and retinopathy of prematurity (31.2%). The survival-to-discharge rate was 63.3%. Cause of death was documented as extreme prematurity in 41% of the inpatient deaths. Birthweight was a significant predictor of mortality (hazard ratio 0.99; 95% confidence interval 0.992 - 0.999). Of the 162 neonates who survived until discharge, 11 died following discharge. Conclusion. Morbidity and mortality rates remain high among ELBW neonates. To improve survival, resources need to be allocated to neonatal resuscitation, surfactant therapy and increasing availability of intensive-care beds.http://www.sajch.org.za/index.php/SAJCH/article/view/1632Publisher's versio

Population level usage of health services, and HIV testing and care, prior to decentralization of antiretroviral therapy in Agago District in rural Northern Uganda: Additional Files

A study protocol developed to investigate health service usage, particularly HIV testing and care, in 2/6 parishes of the Lapono sub-county of northern Uganda, prior to introduction of AntiRetroviral Therapy (ART) services in Lira Kato Health Centre (a local lower-level health centre III). The protocol consists of household and individual questionnaires which were administered to members of each household. These captured individual demographic and health-related information on adults (aged 15–59 years) and socioeconomic data on children living in each household. The protocol was approved by the Joint Clinical Research Centre/Research Ethical Committee (JCRC/REC), Uganda National Council for Science and Technology (UNCST) and Office of the President of the Republic of Uganda

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

BACKGROUND: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz. METHODS: In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2-4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957. FINDINGS: Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2-4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR] 0·99 [95% CI 0·75-1·29]; abacavir vs stavudine: HR 0·88 [0·67-1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00). INTERPRETATION: All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. FUNDING: European Developing Countries Clinical Trials Partnership

Cotrimoxazole reduces systemic inflammation in HIV infection by altering the gut microbiome and immune activation

Wellcome TrustCanadian Institutes of Health ResearchMedical Research CouncilDepartment for International Development under MRC/DFID Concordat agreement and EDCTP2 programme supported by the European UnionMRC Clinical Trials Unit at UC

Impact of seasonality and malaria control interventions on Anopheles density and species composition from three areas of Uganda with differing malaria endemicity

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods: From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results: In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p < 0.001), and An. funestus sensu lato (s.l.) (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005–0.004, p < 0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07–0.33, p < 0.001). Conclusions: LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviourally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority

Differences in body circumferences, skin-fold thicknesses and lipid profiles among HIV-infected African children on and not on stavudine

Purpose of the study To compare body circumferences, skin-fold thickness (SFT) and lipid levels (LL), as measures of lipodystrophy, among antiretroviral therapy (ART)-na&#x00EF;ve and experienced children at enrolment into the CHAPAS-3 trial. Methods HIV-infected children in Uganda and Zambia, either ART-na&#x00EF;ve or on stavudine (d4T) for &#x2265;2 years without clinical lipodystrophy, were randomised to receive d4T, abacavir (ABC) or zidovudine (ZDV) with lamivudine and efavirenz (EFV) or nevirapine. At enrolment, mid-upper arm (MUAC) and calf (CC) circumferences, SFT (biceps, triceps, sub-scapular, supra-iliac) and fasting lipids (total cholesterol (TC), low density lipo-protein (LDL), high density lipoprotein (HDL), triglycerides (TRIG)) were measured. Age/sex adjusted z-scores of MUAC, CC, SFT and the sum of SFT (SSF) used Dutch reference data. ART-na&#x00EF;ve and ART-experienced children were compared with t-tests using Stata v11.0. Summary of results Among 444 children, 224 (51%) were male and 331 (74.5%) ART-na&#x00EF;ve. Mean (sd) CD4% was 19.7% (10.2) versus (vs) 34.2% (7.7) in ART-na&#x00EF;ve vs ART-experienced children. The ART-na&#x00EF;ve were younger than the ART-experienced children (median [IQR] age 2.5 [1.5, 4.0] vs 6.0 [5.5, 7.0] years, p&#x3C;0.0001). Among the ART-experienced, 4/108 (3.7%) were on EFV and median (IQR) d4T use was 3.5 (2.7, 4.2) years. As expected, MUAC, CC, weight-for-age (WAZ) and height-for-age (HAZ) z-scores were lower in the ART-na&#x00EF;ve; the ART-experienced had lower SFT z-scores and higher TC and HDL, but lower TRIG (Table 1). Conclusions Failure-to-thrive likely contributed to lower circumference values in ART-na&#x00EF;ve children. Among the ART-experienced, thinner SFT and higher TC values could be ART (particularly d4T)-related. Normal values, currently unavailable for African children, are being collected. During trial follow-up, we will evaluate the effect of ABC, ZDV and d4T on development of lipodystrophy in na&#x00EF;ve children and its reversibility in d4T-treated children randomised to switch to ZDV/ABC

Non-adherence to long-lasting insecticide treated bednet use following successful malaria control in Tororo, Uganda.

Indoor residual spraying (IRS) and long-lasting insecticide-treated bednets (LLINs) are common tools for reducing malaria transmission. We studied a cohort in Uganda with universal access to LLINs after 5 years of sustained IRS to explore LLIN adherence when malaria transmission has been greatly reduced. Eighty households and 526 individuals in Nagongera, Uganda were followed from October 2017 -October 2019. Every two weeks, mosquitoes were collected from sleeping rooms and LLIN adherence the prior night assessed. Episodes of malaria were diagnosed using passive surveillance. Risk factors for LLIN non-adherence were evaluated using multi-level mixed logistic regression. An age-matched case-control design was used to measure the association between LLIN non-adherence and malaria. Across all time periods, and particularly in the last 6 months, non-adherence was higher among both children <5 years (OR 3.31, 95% CI: 2.30-4.75; p<0.001) and school-aged children 5-17 years (OR 6.88, 95% CI: 5.01-9.45; p<0.001) compared to adults. In the first 18 months, collection of fewer mosquitoes was associated with non-adherence (OR 3.25, 95% CI: 2.92-3.63; p<0.001), and, in the last 6 months, residents of poorer households were less adherent (OR 5.1, 95% CI: 1.17-22.2; p = 0.03). Any reported non-adherence over the prior two months was associated with a 15-fold increase in the odds of having malaria (OR 15.0, 95% CI: 1.95 to 114.9; p = 0.009). Knowledge about LLIN use was high, and the most frequently reported barriers to use included heat and low perceived risk of malaria. Children, particularly school-aged, participants exposed to fewer mosquitoes, and those from poorer households, were less likely to use LLINs. Non-adherence to LLINs was associated with an increased risk of malaria. Strategies, such as behavior change communications, should be prioritized to ensure consistent LLIN use even when malaria transmission has been greatly reduced

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission