The Effect of a Group-Based Mindfulness and Acceptance Training on Psychological Flexibility and Adherence to Antiretroviral Therapy Among Adolescents in Uganda: An Open-Label Randomized Trial

Adherence to antiretroviral therapy (ART) is lower in adolescents with HIV (AWH) than in any other age group, partly due to self-regulatory challenges during development. Mindfulness and acceptance training have been shown to support psychological flexibility, a self-regulatory skill that potentially improves adolescent adherence to medication. We assessed the effect of weekly group-based mindfulness and acceptance training sessions on ART adherence among older adolescents (15–19 years) in Kampala, Uganda. One hundred and twenty-two AWH (median age 17, range 15–19 years, 57% female) receiving care at a public health facility in Kampala were randomized 1:1 to receive 4 weekly 90-min group sessions facilitated by experienced trainers or standard-of-care ART services. The training involved (Session 1) clarifying values, (Session 2) skillfully relating to thoughts, (Session 3) allowing and becoming aware of experiences non-judgmentally, and (Session 4) exploring life through trial and error. At baseline, postintervention, and 3-month follow-up, psychological flexibility was measured using the Avoidance and Fusion Questionnaire for Youth (AFQ-Y8), and self-reported ART adherence was assessed using the Morisky Medication Adherence Scale (MMAS-8). At baseline, the intervention and standard-of-care arms had similar psychological flexibility (AFQ-Y8 score:15.45 ± 0.82; 15.74 ± 0.84) and ART adherence (MMAS-8 score: 5.32 ± 0.24; 5.13 ± 0.23). Retention through the study was moderate (71%). Completion of mindfulness and acceptance training was associated with a significant reduction in psychological inflexibility at the 3-month follow-up (AFQ-Y8 score: 12.63 ± 1.06; 14.05 ± 1.07, P  = .006). However, no significant differences were observed in self-reported adherence to ART at the 3-month follow-up (MMAS-8 score: 5.43 ± 0.23; 4.90 ± 0.33, P  = .522). Group-based mindfulness and acceptance training improved psychological flexibility in this population of adolescents on ART in Uganda but did not significantly improve ART adherence. Future research should explore integrated approaches that combine behavioral management training with other empowerment aspects to improve ART adherence among AWH

Rapid improvements to rural Ugandan housing and their association with malaria from intense to reduced transmission: a cohort study

Summary: Background: Rapid population growth in Africa requires an urgent expansion and improvement of housing options. Improving housing presents a promising opportunity for malaria control by reducing indoor exposure to mosquitoes. We measured recent changes in house design in rural Uganda and evaluated their association with malaria in relation to a mass scale-up of control efforts. Methods: This analysis was part of a cohort study designed to compare temporal changes in malaria incidence from a cohort of children and adults with temporal changes in malaria test positivity rate from health facility surveillance. All children aged 6 months to 10 years (n=384) living in 107 households in Nagongera sub-country, Tororo, Uganda, were given long-lasting insecticide-treated nets and followed between Aug 19, 2011, and June 30, 2017. Repeat rounds of indoor residual spraying of insecticide were initiated on Dec 5, 2014. Socioeconomic data were collected at two timepoints (Sept 25–Oct 9, 2013 and June 21–July 11, 2016) and houses were classified as modern (cement, wood, or metal walls, tiled or metal roof, and closed eaves) or traditional (all other homes). Associations between house design and three outcomes were evaluated before and after the introduction of indoor residual spraying: human biting rate estimated monthly in each household using US Centers for Disease Control and Prevention light traps; parasite prevalence measured routinely by microscopy every 3 months before indoor residual spraying and monthly after indoor residual spraying; and malaria incidence measured by passive surveillance. Findings: The implementation of indoor residual spraying was associated with significant declines in human biting rate (33·5 vs 2·7 Anopheles per house per night after indoor residual spraying, p<0·0001), parasite prevalence (32·0% vs 14·0%, p<0·0001), and malaria incidence (3·0 vs 0·5 episodes per person-year at risk, p<0·0001). The prevalence of modern housing increased from 23·4% in 2013 to 45·4% in 2016 (p=0·001). Compared with traditional houses, modern houses were associated with a 48% reduction in human biting rate before indoor residual spraying (adjusted incidence rate ratio [aIRR] 0·52, 95% CI 0·36–0·73, p=0·0002), and a 73% reduction after indoor residual spraying (aIRR 0·27, 0·17–0·42, p<0·0001). Before indoor residual spraying, there was no association between house type and parasite prevalence, but after indoor residual spraying there was a 57% reduction in the odds of parasitaemia in modern houses compared with traditional houses, controlling for age, sex, and socioeconomic position (adjusted odds ratio 0·43, 95% CI 0·24–0·77, p=0·004). House type was not associated with malaria incidence before or after indoor residual spraying. Interpretation: House design improved rapidly in rural Uganda and was associated with additional reductions in mosquito density and parasite prevalence following the introduction of indoor residual spraying. Changes to house design in endemic Africa, including closing eaves and the replacement of traditional building materials, might help further the gains achieved with more widely accepted malaria control interventions. Funding: US National Institutes of Health, Bill & Melinda Gates Foundation, and Medical Research Council UK

Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial

Background: HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been studied. Methods: We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data officer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). Findings: We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], difference −0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a significant effect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96). Interpretation: Abbreviated HIV counselling and testing did not adversely affect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might affect secondary HIV transmission and improve treatment outcomes. Funding: US National Institute of Mental Health

Assessment of community-level effects of intermittent preventive treatment for malaria in schoolchildren in Jinja, Uganda (START-IPT trial): a cluster-randomised trial

Summary: Background: Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda. Methods: We included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215. Findings: Among 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5–20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73–1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36–1·80, p=0·59). Interpretation: IPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed. Funding: UK Medical Research Council, UK Department for International Development, and Wellcome Trust

Protective efficacy of prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years for the prevention of malaria in Uganda: a randomised controlled open-label trial

Background: WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age until breastfeeding cessation and exclusion of HIV infection. We have previously reported on the effectiveness of continuation of co-trimoxazole prophylaxis up to age 2 years in these children. We assessed the protective efficacy and safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children. Methods: We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. We enrolled HIV-exposed infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding cessation and HIV-status confirmation. At the end of breastfeeding, children who remained HIV-uninfected were randomly assigned (1:1) to discontinue co-trimoxazole or to continue taking it up to age 2 years. At age 2 years, children who continued co-trimoxazole prophylaxis were randomly assigned (1:1) to discontinue or continue prophylaxis from age 2 years to age 4 years. The primary outcome was incidence of malaria (defined as the number of treatments for new episodes of malaria diagnosed with positive thick smear) at age 4 years. For additional comparisons, we observed 48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children who never received prophylaxis. We measured grade 3 and 4 serious adverse events and hospital admissions. All children were followed up to age 5 years and all analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00527800. Findings: 203 HIV-exposed infants were enrolled between Aug 10, 2007, and March 28, 2008. After breastfeeding ended, 185 children were not infected with HIV and were randomly assigned to stop (n=87) or continue (n=98) co-trimoxazole up to age 2 years. At age 2 years, 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were randomly assigned to discontinue (n=46) or continue (n=45) co-trimoxazole from age 2 years to age 4 years. We recorded 243 malaria episodes (2·91 per person-years) in the 45 HIV-exposed children assigned to continue co-trimoxazole until age 4 years compared with 503 episodes (5·60 per person-years) in the 46 children assigned to stop co-trimoxazole at age 2 years (incidence rate ratio 0·53, 95% CI 0·39–0·71; p<0·0001). There was no evidence of malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped co-trimoxazole at age 2 years, but incidence increased significantly in HIV-exposed children who stopped co-trimoxazole at age 4 years (odds ratio 1·78, 95% CI 1·19–2·66; p=0·005). Incidence of grade 3 or 4 serious adverse events, hospital admissions, or deaths did not significantly differ between HIV-exposed, HIV-unexposed, and HIV-infected children. Interpretation: Continuation of co-trimoxazole prophylaxis up to 4 years of age seems safe and efficacious to protect HIV-exposed children living in malaria-endemic areas. Funding: Centers for Disease Control and Prevention Global AIDS Program, Doris Duke Charitable Foundatio