Browsing by Author "Mugo, Nelly"
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Item Comparison of short messaging service self-reported adherence with other adherence measures in a demonstration project of HIV preexposure prophylaxis in Kenya and Uganda(AIDS (London, England), 2018) Musinguzi, Nicholas; Muwonge, Timothy; Ngure, Kenneth; Katabira, Elly; Mugo, Nelly; O’Rourke Burns, Bridget Frances; Baeten, Jared M.; Heffron, Renee; Haberer, Jessica E.Short messaging service (SMS) can collect adherence data on a frequent basis and is relatively anonymous, and therefore could potentially reduce recall and social desirability biases prevalent in other self-reported measures. Methods: We compared SMS self-reported adherence with three self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and two objective adherence measures [electronic adherence monitoring (EAM) and plasma tenofovir levels] using data from HIV-uninfected members of serodiscordant couples enrolled in a preexposure prophylaxis demonstration project in Kenya and Uganda. Results: Of 373 enrolled participants, 256 (69%) were male and median age at enrolment was 29 years (26, 35). Fifty-two percent were from Kenya and median education at enrolment was 10 years (7,12). Overall, median adherence was 90, 75, 85,94 and 79%, respectively, for self-report by SMS, rating, frequency, percentage and EAM adherence. Spearman’s correlation coefficient between SMS and interviewer- administered self-reported measures was 0.18 for rating and frequency, 0.22 for percentage and 0.14 for EAM (all P< 0.001). The estimated difference in average adherence between SMS and self-reported rating, frequency, percentage adherence and EAM was 8.1 (P < 0.001), 0.3 (P = 0.81), −5.2 (P < 0.001) and 9.5 (P < 0.001), respectively. Area under the receiver-operating curve assessing the ability of SMS self-report to discriminate between detectable and undetectable tenofovir was 0.51. Conclusion: Our study found low correlation between SMS self-report and other self-reported and objective adherence measures and did not discriminate between detectable and undetectable plasma tenofovir levels. Future use of SMS self-report should explore alternative means for reducing potential biases.Item Context matters: PrEP adherence is associated with sexual behavior among HIV serodiscordant couples in East Africa(Journal of acquired immune deficiency syndromes, 2017) Haberer, Jessica E.; Ngure, Kenneth; Muwonge, Timothy; Mugo, Nelly; Katabira, Elly; Heffron, Renee; Musinguzi, Nicholas; Bangsberg, David R.; Celum, Connie; Baeten, Jared M.Short message service (SMS) surveys are a promising tool for understanding whether pre-exposure prophylaxis (PrEP) adherence aligns with risk for HIV acquisition— a concept known as prevention-effective adherence. Methods—The Partners Demonstration Project was an open-label study of integrated PrEP and antiretroviral therapy (ART) delivery among high-risk HIV serodiscordant couples in East Africa. HIV-uninfected partners were offered PrEP until their HIV-infected partner had taken ART for ≥6 months. At 2 study sites, HIV-uninfected partners were offered enrollment into the Partners Mobile Adherence to PrEP (PMAP) sub-study based on ongoing PrEP use, personal cell phone ownership, and ability to use SMS. SMS surveys asked about PrEP adherence and sexual activity in the prior 24 hours; these surveys were sent daily for the 7 days prior and 7 days after routine study visits in the Partners Demonstration Project. Results—The PMAP sub-study enrolled 373 HIV-uninfected partners; 69% were male and mean age was 31 years. Participants completed 17,030 of 23,056 SMS surveys sent (74%) with a mean of 47 surveys per participant over 9.8 months of follow-up. While HIV-infected partner use of ART was <6 months, mean reported PrEP adherence was 92% on surveys concurrently reporting sex within the serodiscordant partnership and 84% on surveys reporting no sex (p<0.001). Discussion—SMS surveys provided daily assessment of concurrent PrEP adherence and sexual behavior. Higher PrEP adherence was temporally associated with increased risk for HIV acquisition.Item HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV- 1-Exposed Seronegative Women on Oral Preexposure Prophylaxis(Journal of virology, 2016) Lund, Jennifer M.; Broliden, Kristina; Pyra, Maria N.; Thomas, Katherine K.; Donnell, Deborah; Irungu, Elizabeth; Muwonge, Timothy R.; Mugo, Nelly; Manohar, Madhuri; Jansson, Marianne; Mackelprang, Romel; Marzinke, Mark A.; Baeten, Jared M.; Lingappa, Jairam R.Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P 0.008). Using a cutoff of>90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.Item Pre-exposure prophylaxis differentially alters circulating and mucosal immune cell activation in HSV-2 seropositive women(AIDS (London, England), 2019) Richert-Spuhler, Laura E.; Pattacini, Laura; Plews, Margot; Irungu, Elizabeth; Muwonge, Timothy R.; Katabira, Elly; Mugo, Nelly; Meyers, Adrienne F.A.; Celum, Connie; Baeten, Jared M.; Lingappa, Jairam R.; Lund, Jennifer M.Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an important tool for prevention of new HIV infections, which also reduces subclinical HSV-2 shedding and symptomatic lesions in HIV-negative, HSV-2-seropositive individuals. However, the impact of PrEP on mucosal immunity has not been examined in detail. Design: Here we evaluate paired genital tissue and systemic immune profiles to characterize the immunological effects of PrEP in HIV-negative, HSV-2-seropositive African women sexually exposed to HIV. Methods: We compared local and systemic innate and T-cell characteristics in samples collected during PrEP usage and two months after PrEP discontinuation. Results: We found that frequencies of cervical CCR5+CD4+ cells, regulatory T-cells, and tissue macrophages were significantly reduced during PrEP use compared to after PrEP discontinuation. In contrast, peripheral blood CD4+ and CD8+ T-cells expressing markers of activation and trafficking were increased during PrEP usage. Conclusions: Together, our data are consistent with PrEP altering immunity differentially in the female genital tract compared to circulation in HSV-2+ women. Further study including comparison to HSV-2 negative women is needed to define the overall impact and mechanisms underlying these effects. These results point to the critical need to study the human mucosal compartment to characterize immune responses to mucosal infectionsItem Short message service (SMS) surveys assessing pre-exposure prophylaxis (PrEP) adherence and sexual behavior are highly acceptable among HIV-uninfected members of serodiscordant couples in East Africa: A mixed methods study(AIDS and Behavior, 2019) Muwonge, Timothy R.; Ngure, Kenneth; Katabira, Elly; Mugo, Nelly; Kimemia, Grace; O'Rourke Burns, Bridget Frances; Musinguzi, Nicholas; Bambia, Felix; Baeten, Jared M.; Heffron, Renee; Haberer, Jessica E.Short message service (SMS) surveys are a promising data collection method and were used to measure sexual behavior and adherence to HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected partners of serodiscordant couples enrolled in a sub-study of the Partners Demonstration Project (an open-label study of integrated antiretroviral therapy and PrEP for HIV prevention in Kenya and Uganda). Questionnaires were completed by 142 participants after study exit. Median age was 29 years; 69% were male. Ninety-five percent (95%) felt SMS surveys were “easy” or “very easy”, 74% reported no challenges, and 72% preferred SMS surveys over in-person study visits. Qualitative interviews involving 32 participants confirmed the ease of responding to SMS surveys. Participants also indicated that surveys acted as reminders for adherence to PrEP and condom use and were experienced as support from the study. SMS surveys were generally found to be acceptable in this population and provided real-time context of PrEP use.Item Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection(Cell Reports Medicine, 2020) Hughes, Sean M.; Levy, Claire N.; Calienes, Fernanda L.; Stekler, Joanne D.; Pandey, Urvashi adik; Vojtech, Lucia; Berard, Alicia R.; Birse, Kenzie; Noel-Romas, Laura; Richardson, Brian; Golden, Jackelyn B.; Cartwright, Michael; Collier, Ann C.; Stevens, Claire E.; Curlin, Marcel E.; Holtz, Timothy H.; Mugo, Nelly; Irungu, Elizabeth; Katabira, Elly; Muwonge, Timothy; Lama, Javier R.; Baeten, Jared M.; Burgener, Adam; Lingappa, Jairam R.; McElrath, M. Juliana; Mackelprang, Romel; McGowan, Ian; Cranston, Ross D.; Cameron, Mark J.; Hladik, FlorianTenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here, we assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induces type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r = 0.91) and between the rectum and duodenum (r = 0.81). Gene set testing also indicates stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.