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Background: HIV prevention trials usually require that women of childbearing potential use an effective method of contraception. This is because the effect of most investigational products on unborn babies is unknown. We assessed contraceptive use, prevalence and incidence of pregnancy and associated factors among women in a HIV vaccine preparedness study in Masaka, Uganda., Methods: HIV sero-negative women (18-45 years) at high risk of HIV infection identified through HIV counselling and testing (HCT) were recruited between July 2018 and October 2022. Study procedures included collection of baseline socio-demographics and contraceptive use data, quarterly HCT, counselling on and provision of contraceptive methods onsite/through referral, and 6-monthly urine pregnancy tests. Multivariable Logistic and Poisson regression analyses were conducted to determine factors associated with contraceptive use, prevalence, and incidence of pregnancy., Results: 652 (73%) of 891 women reported contraceptive use at baseline. Contraceptive use was higher in women who were in a relationship/married/cohabiting [adjusted odds ratio (aOR) = 1.60; 95% confidence interval (CI) 1.07-2.40] or divorced/separated/widowed [aOR = 1.86; 95% CI 1.24-2.79] versus those that were single, and among women reporting transactional sex [aOR = 2.10; 95% CI 1.16-3.80] versus those who did not. Baseline pregnancy prevalence was 4% (95% CI 3-6%) and lower in women who reported using long-acting contraceptive methods (aOR = 0.17; 95% CI 0.07-0.39) versus women who did not use these methods. A total of 65 pregnancies over 301.3 person-years of observation (PYO), an incidence rate of 21.6/100 (95% CI 16.9-27.5) PYO, higher among younger women (≤ 24 versus 25 + years, adjusted incidence rate ratio = 1.97; 95% CI 1.15-3.40)., Conclusion: We observed a high pregnancy incidence in this cohort. Innovative strategies that promote sustained and consistent use of highly effective contraceptive methods especially for young women will be critical to the success of HIV prevention trials in this and similar populations., Competing Interests: Declarations. Ethics approval and consent to participants: The study was approved by the UVRI Research Ethics Committee (GC/127/18/03/637), the Uganda National Council for Science and Technology (HS2392) and LSHTM Ethics Committee (26494). All participants provided written informed consent before undergoing study procedures. All pregnant women were referred for antenatal care services. Additionally, pregnant women who tested HIV positive were referred for prevention-of-mother-to-child services. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To investigate the practices of repair that exist for users of mobility assistive products in low resource settings, as well as the psychosocial impact that the repair, or non-repair, of these devices has on users' lives., Materials and Methods: This article collates data on repair practices and the responses from participants on the topic of repair from studies conducted by the authors across four different low resource settings in Kenya, Uganda, Sierra Leone, and Indonesia. This data was then analyzed to identify the common themes found across geographies., Results: Three major models of repair practice emerged from the data: "Individual or Informal Repair in the Community"; "Local Initiatives"; and "Specialist AT Workshop Repair". Additionally, the wider impact on the participants' lives of "Problems & Concerns with Repair"; "Experiences of Breakages & Frequencies of Repair" and the "Impact of Broken Devices" are explored., Conclusions: The results of this analysis demonstrate the paramount importance of community-based repair of devices, and how despite this importance, repair is often overlooked in the planning and design of assistive products and services. There is a need to further incorporate and support these informal contributions as part of the formal provision systems of assistive device.

Background: Daily oral pre-exposure prophylaxis (PrEP) use is highly effective against HIV infection. However, the uptake of PrEP among individuals at high-risk of HIV acquisition in sub-Saharan Africa varies because of availability and acceptability. We assessed the acceptability of PrEP among participants in a prospective HIV vaccine preparedness study in Masaka, southwestern Uganda., Methods: From November 2018 to August 2019, 20 participants (10 female) were purposively selected for in-depth interviews (IDIs) at 3 and 9 months' post-enrolment in the vaccine preparedness study. Four focus group discussions (FGD) (two among men) were conducted with 29 individuals categorized as: younger (18-24 years) men, younger (18-24 years) women, older (≥30 years) men, and older (≥30 years) women. Apart from IDI specific questions on recent life history including work experience, relationship history and places lived, topics for IDIs and FGDs included knowledge of HIV, perceptions of HIV risk (including own risk), knowledge of and use of PrEP. The Theoretical Framework of Acceptability was used to structure a thematic framework approach for data analysis., Results: Participants understood that PrEP was an oral pill taken daily by HIV negative individuals to prevent acquisition of HIV. Overall, interest in and acceptability of PrEP was high, more than half expressed positivity towards PrEP but were not ready to initiate taking it citing the burden of daily oral pill taking, related side effects, stigma and distrust of PrEP. Fourteen participants (from IDI and FGD) initiated PrEP, although some (one FGD and two IDI participants) stopped taking it due to side effects or perceived reduced risk., Conclusion: We observed a keen interest in PrEP initiation among our study participants. However, a limited understanding of PrEP and associated concerns impeded uptake and sustained use. Hence, interventions are needed to address end-user challenges to increase uptake and support adherence., Competing Interests: The authors have declared that no competing interests exist.

This prospective trial investigated the population pharmacokinetics of piperaquine given with dihydroartemisinin to treat uncomplicated malaria in 107 Ugandan children 6 months to 2 years old, an age group previously unstudied. Current weight-based dosing does not adequately address physiological changes in early childhood. Patients were administered standard 3-day oral doses and provided 1,282 capillary plasma concentrations from 218 malaria episodes. Less than 30% of treatments achieved 57 ng/mL on day 7. A three-compartment model with first-order absorption described the data well. Age had a statistically significant effect (P < 0.005) on clearance/bioavailability in a model that accounts for allometric scaling. Simulations demonstrated that higher doses in all children, but especially in those with lower weight for age, are required for adequate piperaquine exposure, although safety and tolerance will need to be established. These findings support other evidence that both weight- and age-specific guidelines for piperaquine dosing in children are urgently needed., Competing Interests: The authors have no conflicts of interest to disclose., (© 2015 American Society for Clinical Pharmacology and Therapeutics.)

Background: Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking., Methods: We conducted a prospective PK/PD study of piperaquine in 107 young children in Uganda. Samples were collected up to 28 days after 218 episodes of malaria treatment, which occurred during follow-up periods of up to 5 months. Malaria follow-up was conducted actively to day 28 and passively to day 63., Results: The median capillary piperaquine concentration on day 7 after treatment was 41.9 ng/mL. Low piperaquine concentrations were associated with an increased risk of recurrent malaria for up to 42 days, primarily in those receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In children not receiving TMP-SMX, low piperaquine concentrations were only modestly associated with an increased risk of recurrent malaria. However, for children receiving TMP-SMX, associations were strong and evident for all sampling days, with PQ concentrations of ≤ 27.3 ng/mL on day 7 associated with a greatly increased risk of recurrent malaria. Notably, of 132 cases of recurrent malaria, 119 had detectable piperaquine concentrations at the time of presentation with recurrent malaria., Conclusions: These piperaquine PK/PD data represent the first in children <2 years of age. Piperaquine exposure on day 7 correlated with an increased risk of recurrent malaria after DP treatment in children receiving TMP-SMX prophylaxis. Interestingly, despite strong associations, infants remained at risk for malaria, even if they had residual levels of piperaquine.

Background: A safe and effective vaginal microbicide could substantially reduce HIV acquisition for women. Consistent gel use is, however, of great importance to ensure continued protection against HIV infection, even with a safe and effective microbicide. We assessed the long-term correlates of consistent gel use in the MDP 301 clinical trial among HIV-negative women in sero-discordant couples in south-west Uganda., Methods: HIV-negative women living with an HIV-infected partner were enrolled between 2005 and 2008, in a three-arm phase III microbicide trial and randomized to 2% PRO2000, 0.5% PRO2000 or placebo gel arms. Follow-up visits continued up to September 2009. The 2% arm was stopped early due to futility and the 229 women enrolled in this arm were excluded from this analysis. Data were analyzed on 544 women on the 0.5% and placebo arms who completed at least 52 weeks of follow-up, sero-converted or became pregnant before 52 weeks. Consistent gel use was defined as satisfying all of the following three conditions: (i) reported gel use at the last sex act for at least 92% of the 26 scheduled visits or at least 92% of the visits attended if fewer than 26; (ii) at least one used applicator returned for each visit for which gel use was reported at the last sex act; (iii) attended at least 13 visits (unless the woman sero-converted or became pregnant during follow-up). Logistic regression models were fitted to investigate factors associated with consistent gel use., Results: Of the 544 women, 473 (86.9%) were followed for at least 52 weeks, 29 (5.3%) sero-converted and 42 (7.7%) became pregnant before their week 52 visit. Consistent gel use was reported by 67.8%. Women aged 25 to 34 years and those aged 35 years or older were both more than twice as likely to have reported consistently using gel compared to women aged 17 to 24 years. Living in a household with three or more rooms used for sleeping compared to one room was associated with a twofold increase in consistent gel use., Conclusion: In rural Uganda younger women and women in houses with less space are likely to require additional support to achieve consistent microbicide gel use., Trial Registration: Protocol Number ISRCTN64716212.

Objective: To assess the safety of dextrin sulphate (DS) gel compared to placebo gel in terms of local and systemic adverse events, and to determine the acceptability of dextrin sulphate gel., Design: A 4-week randomized trial of DS intra-vaginal gel, partially blinded, with placebo and observation control arms. Participants were randomized to use DS gel twice daily, placebo gel twice daily, DS gel pre-sex, or into an observation only arm., Methods: Sexually active women were recruited from post natal and HIV clinics at Nsambya Hospital, Kampala, Uganda. Screening, enrollment and follow-up visits took place every 1 or 2 weeks over an 8-week period and consisted of questionnaire interviews, colposcopy examinations, sexually transmitted infection screen and routine laboratory testing., Results: Out of a total of 172 women screened, 109 were randomized to use DS gel twice daily (65 women), placebo gel twice daily (15 women), DS gel pre-sex (nine women) or into an observation only arm (20 women). Two individuals had abnormal colposcopy findings in the DS twice daily gel use arm. Vaginal bleeding was reported as frequently by participants in the active gel arm as by participants in the placebo and observation only arms. No clinically significant difference was observed between arms in terms of vaginal flora, Candida, haemoglobin, white cell count, platelets, thrombin time, activated partial thromboplastin time, creatinine and aspartate aminotransferase results after 4 weeks of gel use. DS gel appeared to be acceptable to over 95% of the users., Conclusions: Results show a satisfactory safety and acceptability profile of dextrin sulphate gel.

Design: This phase I dose-ranging study of 2 weeks of twice-daily dextrin sulphate (DS), a sulphated polymer with in vitro activity against HIV, was designed in 2 parts. Part A was a randomized, placebo-controlled, double-blind, 3-arm trial (DS4%, DS1%, placebo) in HIV-negative women. In part B, HIV-positive women received DS4% and HIV-negative women were randomized to DS4% or no gel., Results: One hundred women were enrolled from 2 sites (London and Antwerp): DS4% (n = 50, 20 of whom were HIV-positive), DS1% (n = 20), placebo (n = 10) and no gel (n = 20). There were no withdrawals related to adverse events and no cases of epithelial disruption. Spotting was reported by 24 women and numbers were significantly higher in all the gel groups (23 of 80), including placebo, compared with no gel (one of 20) (Fisher exact test P = 0.037). There was no evidence of a dose effect. Safety tests showed no evidence of systemic absorption., Conclusion: Although there was no clear explanation for the spotting, DS4% was well tolerated. It was decided to proceed with DS4% in an expanded safety study in Africa but to restrict entry to low-risk HIV-negative women, include a no-gel group, and monitor intermenstrual bleeding closely.