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Background Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown. Methods Fifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography–mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups. Results 3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues. Conclusions We found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis. Clinical Trials Registration NCT03377608. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer screening program in Uganda is opportunistic and focuses mainly on women aged 25-49 years. Female sex workers (FSWs) are at increased risk of developing invasive cervical cancer. There is limited data regarding the uptake and acceptability of cervical cancer screening among FSWs in Uganda. This study aimed at identifying factors associated with uptake and acceptability of cervical cancer screening among FSWs in Eastern Uganda., Methods: This was a cross-sectional study conducted among 423 FSWs aged 18-49 years attending care at six health facilities serving Key Populations (FSWs, Men who have sex with men, transgender people, people who inject drugs and people in prisons) in the Teso sub-region. Data was collected using structured investigator administered questionnaire and analyzed using Stata statistical software version 15.0 (Stata Corp, Texas, USA). The primary outcome was uptake of cervical cancer screening measured as the proportion of female sex workers who have ever been screened for cervical cancer. Chi-square test was used to compare the differences in uptake of cervical cancer screening by HIV status. Modified Poisson regression model with a robust variance estimator was used to determine association between the outcome variables and selected independent variables including demographic characteristics. Prevalence ratios (PR) with accompanying 95% confidence intervals have been reported. Statistical significance was considered at two-sided p-values ≤ 0.05., Results: The mean age of the participants was 28.1 (±SD = 6.6) years. The self-reported HIV prevalence was 21.5% (n = 91). There were 138 (32.6%) participants who had ever been screened for cervical cancer (uptake), while 397 (93.9%) were willing to be screened (acceptability). There was a significant difference in cervical cancer screening uptake between women living with HIV (WLHIV) and those who were HIV negative, 59.3% vs 26.9% respectively (P < 0.001). The significant factors associated with uptake of cervical cancer screening included living with HIV, adjusted prevalence ratio (aPR) = 1.53 (95%CI: 1.15-2.07), increasing number of biological children, aPR = 1.14 (1.06-1.24) living near a private not for profit (PNFP) facility, aPR = 2.84 (95% CI; 1.68-4.80) and availability of screening services at the nearest health facility, aPR = 1.83 (95% CI, 1.30-2.57). Factors significantly associated with acceptability of cervical cancer screening included being 40 years or older, aPR = 1.22 (95%CI: 1.01-1.47), having a family history of cervical cancer, aPR = 1.05 (1.01-1.10), and living near a PNFP facility, aPR = 1.17 (95% CI, 1.09-1.27) and having ever screened before, aPR = 0.92 (0.86-0.98)., Conclusion: Female sex workers living with HIV are more likely to screen for cervical cancer than the HIV negative clients. Cervical cancer screening uptake is relatively low among the female sex workers. However, majority of the FSWs are willing to be screened for cervical cancer if the services are provided in the nearby healthcare facilities. There is need to make cervical cancer screening services available to all eligible women especially the female sex workers and integrate the services with sexual reproductive health services in general and not just HIV/ART clinics services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Opito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We previously reported the effect of contraception on cervical tenofovir concentrations in Ugandan women with human immunodeficiency virus (HIV). Here we explored the role of cervicovaginal cytokines and drug metabolizing enzymes and transporters (DMETs) to elucidate female genital tract (FGT) drug disposition in a Ugandan cohort., Methods: Cervicovaginal fluid and cervical biopsies were collected from Ugandan women with HIV receiving tenofovir/lamivudine-based therapy and intramuscular depot medroxyprogesterone acetate (n = 25), copper intrauterine device (cuIUD; n = 12), or condoms (n = 13) as contraception. Cytokines were measured in cervicovaginal fluid (CVF). Ectocervical tenofovir diphosphate (TFVdp), lamivudine triphosphate (3TCtp), and deoxyadenosine triphosphate (dATP)/deoxycytidine triphosphate (dCTP) concentrations and immune marker/DMET gene expression were measured in cervical biopsies., Results: Cervical 3TCtp was not correlated with any CVF cytokines. Cervical TFVdp was correlated with IL-10, IL-7, and IL-17 in CVF. CCR5 mRNA expression in cervical biopsies was higher in cuIUD users versus condom users. Using multivariable linear regression, CVF IL-17, tissue dATP, plasma estradiol, and plasma tenofovir were all significant predictors of cervical TFVdp. Tissue dCTP and plasma lamivudine were significant predictors of cervical 3TCtp., Conclusions: TFVdp concentrations in cervix appear to be influenced by local inflammation. In contrast, 3TCtp FGT exposure was not affected by genital inflammation or DMETs. CuIUD users have more immune cells present, which may in turn influence local TFVdp disposition., Main Finding: We investigated changes in tenofovir diphosphate and lamivudine triphosphate due to the microbiome and inflammation. While lamivudine triphosphate was not affected by either, tenofovir diphosphate appeared to be affected by local inflammation. Specifically, Th17 cells may influence tenofovir disposition., Competing Interests: Potential conflicts of interest. F. K. M. has received funding from Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women's willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women's adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64-80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03-1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38-35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70-6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36-10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.

Background: The success of longitudinal trials depends greatly on using effective strategies to retain participants and ensure internal validity, maintain sufficient statistical power, and provide for the generalizability of study results., Objective: This paper describes the challenges and specific strategies used to retain participants in a Phase 2B safety and effectiveness study of daily oral and vaginal tenofovir formulations for the prevention of HIV-1 infection in the MTN-003 (VOICE) trial in Kampala, Uganda., Methods: Once enrolled, participants were seen every 28 days at the research site and their study product was re-filled. Challenges to retention included a mobile population, non-disclosure of study participation to spouse/family, and economic constraints. Strategies used to maintain high participation rates included the use of detailed locator information, a participant tracking database, regular HIV/STI testing, and the formation of close bonds between staff and subjects., Results: We enrolled 322 women out of the 637 screened. The overall retention rate was 95% over a 3 year follow up period. Only 179 (3%) out of the 6124 expected visits were missed throughout study implementation. Reasons for missed visits included: participants thinking that they did not need frequent visits due to their HIV negative status, time constraints due to commercial sex work, and migration for better employment., Conclusions: With the implementation of multi-faceted comprehensive follow-up and retention strategies, we achieved very high retention rates in the MTN-003 study. This paper provides a blueprint for effective participant retention strategies for other longitudinal HIV prevention studies in resource-limited settings in Sub-Saharan Africa.