2,259 results on '"Baeten, Jared M."'
Search Results
2. Differentiated Service Delivery Models for Maintaining HIV Treatment and Prevention Services During Crisis and Disease Outbreaks: Lessons from the COVID-19 Pandemic
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Njuguna, Njambi, Akolo, Christopher, Anzala, Omu, Baeten, Jared M., Heffron, Renee, Mugo, Nelly R., and Bateganya, Moses
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- 2024
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3. Low selection of HIV PrEP refills at private pharmacies among clients who initiated PrEP at public clinics: findings from a mixed-methods study in Kenya
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Ortblad, Katrina F., Kuo, Alexandra P., Mogere, Peter, Roche, Stephanie D., Kiptinness, Catherine, Wairimu, Njeri, Gakuo, Stephen, Baeten, Jared M., and Ngure, Kenneth
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- 2024
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4. Post-trial access to and use of pre-exposure prophylaxis in Durban, South Africa.
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Beesham, Ivana, Milford, Cecilia, Smit, Jenni, Joseph Davey, Dvora L, Baeten, Jared M, Heffron, Renee, Beksinska, Mags, and Mansoor, Leila E
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Humans ,HIV Infections ,Anti-HIV Agents ,Ambulatory Care Facilities ,South Africa ,Female ,Pre-Exposure Prophylaxis ,Oral pre-exposure prophylaxis ,Post-trial access and use ,Young women ,Infectious Diseases ,Prevention ,HIV/AIDS ,Clinical Research ,Clinical Trials and Supportive Activities ,Mental Health ,Good Health and Well Being ,Public Health and Health Services ,Public Health - Abstract
BackgroundHIV endpoint-driven clinical trials increasingly provide oral pre-exposure prophylaxis (PrEP) as standard of prevention during the trial, however, among participants desiring to continue using PrEP at trial exit, little is known about post-trial PrEP access and continued use.MethodsWe conducted one-time, semi-structured, face-to-face, in-depth interviews with 13 women from Durban, South Africa, from November to December 2021. We interviewed women who initiated oral PrEP as part of the HIV prevention package during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial, elected to continue using PrEP at study exit, and were given a 3-month PrEP supply and referred to facilities for PrEP refills at the final trial visit. The interview guide probed for barriers and enablers to post-trial PrEP access, and current and future PrEP use. Interviews were audio-recorded and transcribed. Thematic analysis was facilitated using NVivo.ResultsOf the 13 women, six accessed oral PrEP post-trial exit, but five later discontinued. The remaining seven women did not access PrEP. Barriers to post-trial PrEP access and continued use included PrEP facilities having long queues, inconvenient operating hours, and being located far from women's homes. Some women were unable to afford transport costs to collect PrEP. Two women reported visiting their local clinics and requesting PrEP but were informed that PrEP was unavailable at the clinic. Only one woman was still using PrEP at the time of the interview. She reported that the PrEP facility was located close to her home, staff were friendly, and PrEP education and counselling were provided. Most women not on PrEP reported wanting to use it again, particularly if barriers to access could be alleviated and PrEP was easily available at facilities.ConclusionsWe identified several barriers to post-trial PrEP access. Strategies to enhance PrEP access such as a reduction in waiting queues, convenient facility operating hours, and making PrEP more widely available and accessible are needed. It is also worth noting that oral PrEP access has expanded in South Africa from 2018 till now and this could improve access to PrEP for participants exiting trials who desire to continue PrEP.
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- 2023
5. Provider perspectives on service delivery modifications to maintain access to HIV pre‐exposure prophylaxis during the COVID‐19 pandemic: qualitative results from a PrEP implementation project in Kenya
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Velloza, Jennifer, Roche, Stephanie D, Owidi, Emmah J, Irungu, Elizabeth M, Dollah, Annabell, Kwach, Benn, Thuo, Nicholas B, Morton, Jennifer F, Mugo, Nelly, Bukusi, Elizabeth A, O'Malley, Gabrielle, Ngure, Kenneth, Baeten, Jared M, Mugwanya, Kenneth K, and Team, for the Partners Scale‐Up Project
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Infectious Diseases ,Health Services ,HIV/AIDS ,Prevention ,Clinical Research ,Infection ,Good Health and Well Being ,Humans ,Female ,Adult ,Male ,HIV Infections ,Pre-Exposure Prophylaxis ,Pandemics ,Kenya ,COVID-19 ,Anti-HIV Agents ,adaptation ,HIV ,pre-exposure prophylaxis ,serodiscordant couples ,Partners Scale-Up Project Team ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionHIV pre-exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID-19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID-19 pandemic.MethodsSince 2017, the Partners Scale-Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May-Aug 2020) and again after some decline in COVID-19 rates (Nov-Jan 2021). We analysed data using inductive memo-writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME).ResultsWe interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29-34) and 2.3 years of experience delivering PrEP (IQR: 2-3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple-month PrEP refills, intensifying phone-based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical-room PrEP dispensing, pre-packing PrEP and task-shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides.ConclusionsCOVID-19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post-pandemic.
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- 2023
6. Oral preexposure prophylaxis uptake, adherence, and persistence during periconception periods among women in South Africa
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Matthews, Lynn T., Jaggernath, Manjeetha, Kriel, Yolandie, Smith, Patricia M., Haberer, Jessica E., Baeten, Jared M., Hendrix, Craig W., Ware, Norma C., Moodley, Pravi, Pillay, Melendhran, Bennett, Kara, Bassler, John, Psaros, Christina, Hurwitz, Kathleen E., Bangsberg, David R., and Smit, Jennifer A.
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- 2024
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7. Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results
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Barnabas, Ruanne V., Brown, Elizabeth R., Onono, Maricianah A., Bukusi, Elizabeth A., Njoroge, Betty, Winer, Rachel L., Galloway, Denise A., Pinder, Leeya F., Donnell, Deborah, N. Wakhungu, Imelda, Biwott, Charlene, Kimanthi, Syovata, Heller, Kate B., Kanjilal, Diane G., Pacella, Daniel, Morrison, Susan, A. Rechkina, Elena, L. Cherne, Stephen, Schaafsma, Torin T., McClelland, R. Scott, Celum, Connie, Baeten, Jared M., and Mugo, Nelly R.
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- 2023
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8. Performance of Multiple Adherence Measures for pre-exposure Prophylaxis (PrEP) Among Young Women in Kenya
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Musinguzi, Nicholas, Ngure, Kenneth, Bukusi, Elizabeth A., Mugo, Nelly R., Baeten, Jared M., Anderson, Peter L., and Haberer, Jessica E.
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- 2023
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9. Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials.
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Garcia-Cremades, Maria, Vučićević, Katarina, Hendrix, Craig W, Jayachandran, Priya, Jarlsberg, Leah, Grant, Robert, Celum, Connie L, Martin, Michael, Baeten, Jared M, Marrazzo, Jeanne, Anderson, Peter, Choopanya, Kachit, Vanichseni, Suphak, Glidden, David V, and Savic, Radojka M
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HIV/AIDS ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Prevention ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Female ,Humans ,Male ,Anti-HIV Agents ,Data Analysis ,Emtricitabine ,HIV ,HIV Infections ,Medication Adherence ,Pre-Exposure Prophylaxis ,Tenofovir ,Clinical Trials ,Phase III as Topic ,preexposure prophylaxis ,drug protective plasma concentration ,HIV outcome ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundDaily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.MethodsParticipant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.ResultsAround 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.ConclusionsUsing the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.
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- 2022
10. High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study
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Beesham, Ivana, Parikh, Urvi M, Mellors, John W, Davey, Dvora L Joseph, Heffron, Renee, Palanee-Phillips, Thesla, Bosman, Shannon L, Beksinska, Mags, Smit, Jennifer, Ahmed, Khatija, Makkan, Heeran, Selepe, Pearl, Louw, Cheryl, Kotze, Philip, Hofmeyr, G Justus, Singata‐Madliki, Mandisa, Rees, Helen, Baeten, Jared M, and Wallis, Carole
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Antimicrobial Resistance ,Clinical Research ,HIV/AIDS ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Genetics ,Development of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Drug Resistance ,Viral ,Female ,Genotype ,HIV Infections ,HIV Seropositivity ,HIV-1 ,Humans ,Mutation ,Prospective Studies ,Reverse Transcriptase Inhibitors ,South Africa ,Young Adult ,antiretroviral resistance ,women ,pretreatment resistance ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundPretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.MethodsHIV-uninfected, sexually active women, aged 18-35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.ResultsWe sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs.ConclusionsThe high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.
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- 2022
11. Exploring adolescent girls and young women's PrEP‐user profiles: qualitative insights into differentiated PrEP delivery platform selection and engagement in Cape Town, South Africa
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Rousseau, Elzette, Sikkema, Kathleen J., Julies, Robin F., Mazer, Katelyn, O'Malley, Gabrielle, Heffron, Renee, Morton, Jennifer F., Johnson, Rachel, Celum, Connie, Baeten, Jared M., and Bekker, Linda‐Gail
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HIV testing -- Usage ,Courier services -- Usage ,Health care industry -- Usage -- Social aspects ,Sexually transmitted diseases -- Prevention ,Young women -- Social aspects -- Usage ,Reproductive health -- Usage -- Social aspects ,Teenage girls -- Usage -- Social aspects ,Health care industry ,Health - Abstract
: Introduction: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre‐exposure prophylaxis (PrEP). With ongoing PrEP scale‐up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. Methods: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16−25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community‐based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light‐touch PrEP refill services incorporating rapid HIV self‐testing. We conducted in‐depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP‐use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision‐making and habits related to PrEP access to inform market segmentation. Results: We interviewed 26 AGYW (median age 20) PrEP‐users between November 2020 and March 2021. AGYW PrEP‐users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The “Social PrEP‐user” preferred PrEP delivery in peer spaces, such as youth clubs or adolescent‐friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The “Convenient PrEP‐user” favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception‐PrEP refill visits (mobile and government clinic). The “Independent PrEP‐user” preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The “Discreet PrEP‐user” highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self‐testing had minimal influence on PrEP delivery choice. Conclusions: Market segmentation of AGYW characterizes different types of PrEP‐users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits., INTRODUCTION The past 5 years have seen the global inclusion of oral pre‐exposure prophylaxis (PrEP) into national guidelines as a key biomedical HIV prevention method, with many countries planning to [...]
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- 2024
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12. Population-Level Correlation Between Incidence of Curable Sexually Transmitted Infections and Human Immunodeficiency Virus (HIV)-1 Among African Women Participating in HIV-1 Pre-Exposure Prophylaxis Trials.
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Hunidzarira, Portia, Brown, Elizabeth R, Chirenje, Z Mike, Hillier, Sharon L, Marrazzo, Jeanne M, Palanee-Phillips, Thesla, Kiweewa, Flavia M, and Baeten, Jared M
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Biomedical and Clinical Sciences ,Public Health ,Clinical Sciences ,Health Sciences ,Medical Microbiology ,Mental Health ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Clinical Research ,Infectious Diseases ,Prevention ,Sexually Transmitted Infections ,2.2 Factors relating to the physical environment ,Aetiology ,Infection ,Good Health and Well Being ,Chlamydia Infections ,Chlamydia trachomatis ,Female ,HIV Infections ,HIV-1 ,Humans ,Incidence ,Neisseria gonorrhoeae ,Pre-Exposure Prophylaxis ,Prevalence ,Sexually Transmitted Diseases ,clinical trial design ,HIV incidence ,sexually transmitted infections ,women ,MTN-003/VOICE and MTN-020/ASPIRE Study Teams ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundHighly efficacious oral pre-exposure prophylaxis (PrEP) is the global standard for human immunodeficiency virus (HIV)-1 prevention, including in clinical trials of novel PrEP agents using active-comparator designs. The analysis assessed whether incident sexually transmitted infections (STIs) can serve as a surrogate indicator of HIV-1 incidence that might occur in the absence of PrEP.MethodsWe analyzed data from 3256 women randomized to placebo groups of oral and vaginal PrEP trials (MTN-003/VOICE and MTN-020/ASPIRE). Regression modeling assessed the correlation between incident individual STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, each considered separately) and incident HIV-1.ResultsAcross 18 sites in 4 countries (Malawi, South Africa, Uganda, Zimbabwe), STI and HIV-1 incidences were high: HIV-1 4.9, N gonorrhoeae 5.3, C trachomatis 14.5, and T vaginalis 7.1 per 100 person-years. There was limited correlation between HIV-1 incidence and incidence of individual STIs: N gonorrhoeae (r = 0.02, P = .871), C trachomatis (r = 0.49, P =
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- 2022
13. Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial
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Beesham, Ivana, Mansoor, Leila E, Davey, Dvora L Joseph, Palanee-Phillips, Thesla, Smit, Jenni, Ahmed, Khatija, Selepe, Pearl, Louw, Cheryl, Singata-Madliki, Mandisa, Kotze, Philip, Heffron, Renee, Parikh, Urvi M, Wiesner, Lubbe, Rees, Helen, Baeten, Jared M, and Beksinska, Mags
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Public Health ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Clinical Research ,Prevention ,Sexually Transmitted Infections ,Clinical Trials and Supportive Activities ,Infectious Diseases ,HIV/AIDS ,Contraception/Reproduction ,Infection ,Good Health and Well Being ,Acquired Immunodeficiency Syndrome ,Adolescent ,Adult ,Anti-HIV Agents ,Female ,HIV Infections ,Humans ,Medication Adherence ,Pre-Exposure Prophylaxis ,South Africa ,Tenofovir ,Young Adult ,HIV prevention ,women ,plasma tenofovir ,oral PrEP ,clinical trials ,Africa ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundHIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.MethodsECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification.ResultsOf 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83-104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83).ConclusionsOver a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end.Clinical trial numberNCT02550067.
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- 2022
14. Modeling the Probability of HIV Infection over Time in High-Risk Seronegative Participants Receiving Placebo in Five Randomized Double-Blind Placebo-Controlled HIV Pre-Exposure Prophylaxis Trials: A Patient-Level Pooled Analysis.
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Garcia-Cremades, Maria, Hendrix, Craig W, Jayachandran, Priya, Strydom, Natasha, Jarlsberg, Leah, Grant, Robert, Celum, Connie L, Martin, Michael, Baeten, Jared M, Marrazzo, Jeanne, Anderson, Peter, Choopanya, Kachit, Vanichseni, Suphak, Glidden, David V, and Savic, Radojka M
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HIV prevention trials ,key and vulnerable populations ,modeling ,risk factors ,risk phenotypes ,Clinical Research ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Prevention ,Infectious Diseases ,Sexual and Gender Minorities (SGM/LGBT*) ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Pharmacology and Pharmaceutical Sciences - Abstract
The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.
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- 2022
15. HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial
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Wohl, David A, Spinner, Christoph D, Flamm, Jason, Hare, C Bradley, Doblecki-Lewis, Susanne, Ruane, Peter J, Molina, Jean-Michel, Mills, Anthony, Brinson, Cynthia, Ramgopal, Moti, Clarke, Amanda, Crofoot, Gordon, Martorell, Claudia, Carter, Christoph, Cox, Stephanie, Hojilla, J Carlo, Shao, Yongwu, Das, Moupali, Kintu, Alexander, Baeten, Jared M, Grant, Robert M, Mounzer, Karam, and Mayer, Kenneth
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- 2024
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16. Peer PrEP referral + HIV self-test delivery for PrEP initiation among young Kenyan women: study protocol for a hybrid cluster-randomized controlled trial
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Wairimu, Njeri, Malen, Rachel C., Reedy, Adriana M., Mogere, Peter, Njeru, Irene, Culquichicón, Carlos, McGowan, Maureen, Gao, Fei, Baeten, Jared M., Ngure, Kenneth, and Ortblad, Katrina F.
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- 2023
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17. Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial
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Brown, Bryan P., Feng, Colin, Tanko, Ramla F., Jaumdally, Shameem Z., Bunjun, Rubina, Dabee, Smritee, Happel, Anna-Ursula, Gasper, Melanie, Nyangahu, Donald D., Onono, Maricianah, Nair, Gonasagrie, Palanee-Phillips, Thesla, Scoville, Caitlin W., Heller, Kate, Baeten, Jared M., Bosinger, Steven E., Burgener, Adam, Passmore, Jo-Ann S., Heffron, Renee, and Jaspan, Heather B.
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- 2023
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18. Prevalent human papillomavirus infection increases the risk of HIV acquisition in African women: advancing the argument for human papillomavirus immunization
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Liu, Gui, Mugo, Nelly R, Brown, Elizabeth R, Mgodi, Nyaradzo M, Chirenje, Zvavahera M, Marrazzo, Jeanne M, Winer, Rachel L, Mansoor, Leila, Palanee-Phillips, Thesla, Siva, Samantha S, Naidoo, Logashvari, Jeenarain, Nitesha, Gaffoor, Zakir, Nair, Gonasagrie L, Selepe, Pearl, Nakabiito, Clemensia, Mkhize, Baningi, Mirembe, Brenda Gati, Taljaard, Marthinette, Panchia, Ravindre, Baeten, Jared M, Balkus, Jennifer E, Hladik, Florian, Celum, Connie L, and Barnabas, Ruanne V
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Sexually Transmitted Infections ,Infectious Diseases ,Cancer ,Cervical Cancer ,Prevention ,Immunization ,HIV/AIDS ,Adolescent Sexual Activity ,Clinical Research ,HPV and/or Cervical Cancer Vaccines ,Vaccine Related ,Pediatric ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Adult ,Alphapapillomavirus ,Case-Control Studies ,Female ,HIV Infections ,Humans ,Papillomaviridae ,Papillomavirus Infections ,Papillomavirus Vaccines ,Prevalence ,Risk Factors ,Vaccination ,Young Adult ,adolescent girls and young women ,cervical cancer ,HIV acquisition ,human papillomavirus ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveVaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa.DesignA case-control study.MethodsWe matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs.ResultsMean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2).ConclusionHPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence.
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- 2022
19. Provider–client rapport in pre-exposure prophylaxis delivery : a qualitative analysis of provider and client experiences of an implementation science project in Kenya
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Omollo, Victor, Roche, Stephanie D., Mogaka, Felix, Odoyo, Josephine, Barnabee, Gena, Bukusi, Elizabeth A., Katz, Ariana W. K., Morton, Jennifer, Johnson, Rachel, Baeten, Jared M., Celum, Connie, and O’Malley, Gabrielle
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- 2022
20. Effect of differentiated direct‐to‐pharmacy PrEP refill visits supported with client HIV self‐testing on clinic visit time and early PrEP continuation
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Zewdie, Kidist Belay, Ngure, Kenneth, Mwangi, Margaret, Mwangi, Dominic, Maina, Simon, Etyang, Lydia, Maina, Gakuo, Ogello, Vallery, Owidi, Emmah, Mugo, Nelly R., Baeten, Jared M., and Mugwanya, Kenneth K.
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Self-examination, Medical -- Methods ,Patient compliance -- Evaluation ,HIV infection -- Prevention ,Health - Abstract
: Introduction: Delivery of oral pre‐exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic‐level barriers including lengthy clinic visits may threaten client continuation on PrEP. Methods: Between January 2020 and January 2022, we conducted a quasi‐experimental evaluation of differentiated direct‐to‐pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct‐to‐pharmacy for PrEP refill, client HIV self‐testing (HIVST), client navigator, and pharmacist‐led rapid risk assessment and dispensing. Two other clinics with comparable size and client volume served as contemporaneous controls with the usual clinic flow. PrEP continuation was evaluated by visit attendance and pharmacy refill records, and time and motion studies were conducted to determine time spent in the clinics. Dried blood spots were collected to test for tenofovir‐diphosphate (TFV‐DP) at random visits. We used logistic regression to assess the intervention effect on PrEP continuation and the Wilcoxon rank sum test to assess the effect on clinic time. Results: Overall, 746 clients were enrolled, 366 at control clinics (76 during pre‐implementation and 290 during implementation phase), and 380 at direct‐to‐pharmacy clinics (116 during pre‐implementation and 264 during implementation phase). Prior to implementation, the intervention and control clinics were comparable on client characteristics (female: 51% vs. 47%; median age: 33 vs. 33 years) and PrEP continuation (35% vs. 37% at 1 month, and 37% vs. 39% at 3 months). The intervention reduced total time spent at the clinic by 35% (median of 51 minutes at control vs. 33 minutes at intervention clinics; p Conclusions: A client‐centred PrEP delivery approach with direct‐to‐pharmacy PrEP refill visits plus client HIVST significantly reduced clinic visit time by more than one‐third and improved PrEP continuation in public health HIV clinics in Kenya., INTRODUCTION Oral pre‐exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy [1–3]; however, maximizing access and continuation is a key challenge for optimizing the overall public health impact of [...]
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- 2024
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21. My Way: development and preliminary evaluation of a novel delivery system for PrEP and other sexual health needs of young women in Western Kenya
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Haberer, Jessica E., Oware, Kevin, Juma, Lawrence, Nyerere, Bernard, Momanyi, Vincent, Odoyo, Josephine, Garrison, Lindsey, Bhagat, Julita, Musinguzi, Nicholas, Baeten, Jared M., Siegler, Aaron, and Bukusi, Elizabeth A.
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Antiviral agents -- Distribution ,Women's health services -- Management ,HIV infection -- Prevention ,Company business management ,Company distribution practices ,Health - Abstract
: Introduction: Young women in sub‐Saharan Africa are a priority population for HIV prevention, yet challenges with adherence and persistence to HIV pre‐exposure prophylaxis (PrEP) are common. This study involved the development and pilot testing of My Way—a novel delivery system for PrEP and co‐packaged sexual health services. Methods: My Way was developed in Kisumu, Kenya through a user‐centred design process (2020). The intervention involves peer‐delivery and support for HIV testing and PrEP use, self‐collected vaginal swabs for sexually transmitted infection (STI) testing, pregnancy testing, oral contraceptive pills, self‐injectable medroxyprogesterone and/or condoms. My Way was assessed among 16‐ to 24‐year‐old sexually active women in a randomized controlled trial versus standard of care (SoC; 2021–2022). Use of PrEP and other sexual health services were tracked at 1, 3 and 6 months for feasibility. Acceptability was determined by questionnaire. The effect of the intervention on tenofovir diphosphate (TFV‐DP) levels was assessed by chi‐square test (primary outcome); other predictors were explored with regression analysis. Results: Among 150 women, the median age was 22 years and the median number of sexual partners was 2. Moderate/severe depression was common (60%). In the intervention arm, peers made 88% (198/225) of possible kit deliveries (177 with PrEP) and 49 STIs were diagnosed. In the SoC arm, 24% (55/225) of expected clinic visits occurred (53 with PrEP); no STI testing was performed. TVF‐DP was detected in 16 participants at 6 months: 16% (12/75) in the intervention arm versus 5% (4/75) in the SoC arm (p = 0.03). Persistence among those with ongoing HIV prevention needs (i.e. prevention‐effective persistence) was 18% (12/67) versus 7% (4/56; p = 0.08). No women acquired HIV. The intervention was significantly associated with detectable TFV‐DP (OR 3.5, 1.1‐11.4; p = 0.04); moderate/severe depression trended towards an association with TFV‐DP (OR 0.2, 0.03–1.6; p = 0.13). Conclusions: My Way is a promising delivery system for PrEP and other sexual health services among young women in Western Kenya. We found high feasibility and acceptability. PrEP use was modest, but higher with My Way compared to SoC. Long‐acting PrEP formulations may overcome important barriers to PrEP use and should be explored in combination with the My Way delivery model., INTRODUCTION Young women in sub‐Saharan Africa (sSA) are a priority population for HIV prevention, accounting for 63% of all new cases in 2021 [1]. Approximately six of seven new HIV [...]
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- 2024
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22. Examining Associations Between Mental Health, IPV Exposure, HIV Risk Behaviors, and PrEP Use in South African Women: An Analysis of Data from the Charisma Study
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Triplett, Noah S., Roberts, Sarah T., Hartmann, Miriam, Wagner, Danielle, Reddy, Krishnaveni R., Mathebula, Florence, Tolley, Elizabeth E., Baeten, Jared M., Palanee-Phillips, Thesla, and Montgomery, Elizabeth T.
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- 2023
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23. Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study
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Eron, Joseph J, Little, Susan J, Crofoot, Gordon, Cook, Paul, Ruane, Peter J, Jayaweera, Dushyantha, VanderVeen, Laurie A, DeJesus, Edwin, Zheng, Yanan, Mills, Anthony, Huang, Hailin, Waldman, Sarah E, Ramgopal, Moti, Gorgos, Linda, Collins, Sean E, Baeten, Jared M, and Caskey, Marina
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- 2024
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24. Correlates of Dapivirine Vaginal Ring Acceptance among Women Participating in an Open Label Extension Trial
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Mirembe, Brenda Gati, Cabrera, Maria Valdez, van der Straten, Ariane, Nakalega, Rita, Cobbing, Mandy, Mgodi, Nyaradzo M., Palanee-Phillips, Thesla, Mayo, Ashley J., Dadabhai, Sufia, Mansoor, Leila E., Siva, Samantha, Nair, Gonasagrie, Chinula, Lameck, Akello, Carolyne A., Nakabiito, Clemensia, Soto-Torres, Lydia E., Baeten, Jared M., and Brown, Elizabeth R.
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- 2023
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25. Multi-level Factors Driving Pre-exposure Prophylaxis Non-initiation Among Young Women at High Risk for HIV in Kenya
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Katz, Ingrid T., Ngure, Kenneth, Kamolloh, Kevin, Ogello, Vallery, Okombo, Moses, Thuo, Nicholas B., Owino, Esther, Garrison, Lindsey E., Lee, Yeonsoo S., Nardell, Maria F., Anyacheblu, Chiemelie, Bukusi, Elizabeth, Mugo, Nelly, Baeten, Jared M., and Haberer, Jessica E.
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- 2023
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26. “Yes, I’m reminded, but it doesn’t mean I’m taking them”: Experiences with Short Message Service Reminder Use in Real-time Monitoring of HIV PrEP among Young Women in Kenya
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Ogello, Vallery, Ngure, Kenneth, Thuo, Nicholas, Burns, Bridget, Rono, Bernard, Oware, Kevin, Kiptiness, Catherine, Mugo, Nelly, Bukusi, Elizabeth, Garrison, Lindsey, Baeten, Jared M., and Haberer, Jessica E.
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- 2023
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27. Trajectories of Oral PrEP Adherence Among Young Kenyan Women: Implications for Promoting Effective PrEP Use
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Musinguzi, Nicholas, Pyra, Maria, Bukusi, Elizabeth A., Mugo, Nelly R., Baeten, Jared M., and Haberer, Jessica E.
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- 2023
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28. A novel “HIV salience and Perception” scale is associated with PrEP dispensing and adherence among adolescent girls and young women in Kampala, Uganda
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Velloza, Jennifer, Mujugira, Andrew, Muwonge, Timothy, Boyer, Jade, Nampewo, Olivia, Badaru, Josephine, Ssebuliba, Timothy, Stalter, Randy M., Stein, Gabrielle, Baeten, Jared M., Celum, Connie, and Heffron, Renee
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- 2023
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29. CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions.
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Richert-Spuhler, Laura E, Mar, Corinne M, Shinde, Paurvi, Wu, Feinan, Hong, Ting, Greene, Evan, Hou, Sharon, Thomas, Katherine, Gottardo, Raphael, Mugo, Nelly, de Bruyn, Guy, Celum, Connie, Baeten, Jared M, Lingappa, Jairam R, Lund, Jennifer M, Partners in Prevention HSV/HIV Transmission Study, and and the Partners PrEP Study Teams
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Partners in Prevention HSV/HIV Transmission Study ,and the Partners PrEP Study Teams ,CD101 ,HIV acquisition ,T cell ,host genetic variation ,immune quiescence ,inflammation ,inflammatory homeostasis - Abstract
We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.
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- 2021
30. Using the adherence‐efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background HIV incidence: a secondary analysis of a randomized, controlled trial
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Glidden, David V, Das, Moupali, Dunn, David T, Ebrahimi, Ramin, Zhao, Yongwu, Stirrup, Oliver T, Baeten, Jared M, and Anderson, Peter L
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HIV/AIDS ,Sexual and Gender Minorities (SGM/LGBT*) ,Prevention ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Bayes Theorem ,Emtricitabine ,Female ,HIV Infections ,Homosexuality ,Male ,Humans ,Male ,Pre-Exposure Prophylaxis ,Sexual and Gender Minorities ,Tenofovir ,counterfactual ,PrEP ,clinical trial design ,tenofovir alafenamide ,tenofovir disoproxil fumarate ,Bayesian inference ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Abstract
IntroductionRandomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).MethodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.ResultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.ConclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.
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- 2021
31. Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial
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Nair, Gonasagrie, Celum, Connie, Szydlo, Daniel, Brown, Elizabeth R, Akello, Carolyne A, Nakalega, Rita, Macdonald, Pippa, Milan, Gakiema, Palanee-Phillips, Thesla, Reddy, Krishnaveni, Tahuringana, Eunice, Muhlanga, Felix, Nakabiito, Clemensia, Bekker, Linda-Gail, Siziba, Bekezela, Hillier, Sharon L, Baeten, Jared M, Garcia, Morgan, Johnson, Sherri, McClure, Tara, Levy, Lisa, Livant, Edward, Jacobson, Cindy, Soto-Torres, Lydia, van der Straten, Ariane, Hosek, Sybil, Rooney, James F, Steytler, John, Bunge, Katherine, Parikh, Urvi, Hendrix, Craig, Anderson, Peter, and Ngure, Kenneth
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- 2023
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32. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial
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Avihingsanon, Anchalee, Lu, Hongzhou, Leong, Chee Loon, Hung, Chien-Ching, Koenig, Ellen, Kiertiburanakul, Sasisopin, Lee, Man-Po, Supparatpinyo, Khuanchai, Zhang, Fujie, Rahman, Sophia, D'Antoni, Michelle L, Wang, Hongyuan, Hindman, Jason T, Martin, Hal, Baeten, Jared M, and Li, Taisheng
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- 2023
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33. Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection
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Barnabas, Ruanne V, Brown, Elizabeth R, Bershteyn, Anna, Stankiewicz Karita, Helen C, Johnston, Christine, Thorpe, Lorna E, Kottkamp, Angelica, Neuzil, Kathleen M, Laufer, Miriam K, Deming, Meagan, Paasche-Orlow, Michael K, Kissinger, Patricia J, Luk, Alfred, Paolino, Kristopher, Landovitz, Raphael J, Hoffman, Risa, Schaafsma, Torin T, Krows, Meighan L, Thomas, Katherine K, Morrison, Susan, Haugen, Harald S, Kidoguchi, Lara, Wener, Mark, Greninger, Alexander L, Huang, Meei-Li, Jerome, Keith R, Wald, Anna, Celum, Connie, Chu, Helen Y, and Baeten, Jared M
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Clinical Trials and Supportive Activities ,Clinical Research ,Vaccine Related ,Pneumonia ,Emerging Infectious Diseases ,Prevention ,Lung ,Infectious Diseases ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Antiviral Agents ,COVID-19 ,COVID-19 Nucleic Acid Testing ,Double-Blind Method ,Female ,Humans ,Hydroxychloroquine ,Male ,Middle Aged ,Post-Exposure Prophylaxis ,SARS-CoV-2 ,Time Factors ,Treatment Outcome ,United States ,Young Adult ,COVID-19 Drug Treatment ,Hydroxychloroquine COVID-19 PEP Study Team ,Clinical Sciences ,Public Health and Health Services - Abstract
BackgroundEffective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.ObjectiveTo test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.DesignHousehold-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).SettingNational U.S. multicenter study.ParticipantsClose contacts recently exposed ( 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026).LimitationThe delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.ConclusionThis rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.Primary funding sourceBill & Melinda Gates Foundation.
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- 2021
34. Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study
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Baeten, Jared M, Palanee-Phillips, Thesla, Mgodi, Nyaradzo M, Mayo, Ashley J, Szydlo, Daniel W, Ramjee, Gita, Mirembe, Brenda Gati, Mhlanga, Felix, Hunidzarira, Portia, Mansoor, Leila E, Siva, Samantha, Govender, Vaneshree, Makanani, Bonus, Naidoo, Logashvari, Singh, Nishanta, Nair, Gonasagrie, Chinula, Lameck, Parikh, Urvi M, Mellors, John W, Balán, Iván C, Ngure, Kenneth, van der Straten, Ariane, Scheckter, Rachel, Garcia, Morgan, Peda, Melissa, Patterson, Karen, Livant, Edward, Bunge, Katherine, Singh, Devika, Jacobson, Cindy, Jiao, Yuqing, Hendrix, Craig W, Chirenje, Zvavahera M, Nakabiito, Clemensia, Taha, Taha E, Jones, Judith, Torjesen, Kristine, Nel, Annalene, Rosenberg, Zeda, Soto-Torres, Lydia E, Hillier, Sharon L, Brown, Elizabeth R, Aanyu, Dorothy, Abima, John, Abullarade, Janne, Agarwal, Priyanka, Ahluwalia, Surabhi, Akasiima, Simon Africa, Akello, Carolyne Agwau, Albert, Samuel, Alphale, Motsamai, Alphonse, Calins, Apeduno, Lucy, Aranda, Sara, Aridor, Orly, Arnolds, Shakeera, Asiimwe, Prossy, Atujuna, Millicent, Atwebembere, Didas, Baboolall, Lakshmi, Badana, Kiran, Balamusani, David, Banda, Gabriel, Banda, Towera Whitney, Baugh, Jennifer, Baziira, James Amos, Beamer, May, Bebeza, Sivuyisiwe Asanda, Bekker, Linda-Gail, Bell, Ian, Bemer, Meagan, Berman, Richard, Berthiaume, Jennifer, Bezak, Linda, Bhagwandin, Yashveer, Bhayat, Hassen Anwar, Bhengu, Nokulunga, Bhengu, Sonto, Bhoola, Aruna, Biira, Florence Asiimwe, Bittoni, Daniel, Black, Roberta, Blose, Nombuso Jacqueline, Boks, Pearl, Bolton, Stephen Gordon, Botya, Phathiswa, Brown, Amanda, Brown, Elizabeth, Brown, Helen, Bruce, Robyn Helen, Bukenya, Luke Erismus, Bukirwa, Aidah, Bunts, Lisa, Buthelezi, Fezile, Buthelezi, Mbongeleni William, Buthelezi, Samkelisiwe Dumisile, and Byogero, Rose
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Prevention ,HIV/AIDS ,Mental Health ,Infectious Diseases ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Administration ,Intravaginal ,Adult ,Anti-HIV Agents ,Contraceptive Devices ,Female ,Female ,HIV Infections ,HIV-1 ,Humans ,Malawi ,Patient Compliance ,Patient Safety ,Pyrimidines ,Seroconversion ,South Africa ,Tenofovir ,Treatment Outcome ,Uganda ,Zimbabwe ,MTN-025/HOPE Study Team ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundTwo phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.MethodsWe did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037.FindingsBetween July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p
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- 2021
35. Urine Tenofovir Levels Measured Using a Novel Immunoassay Predict Human Immunodeficiency Virus Protection
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Stalter, Randy M, Baeten, Jared M, Donnell, Deborah, Spinelli, Matthew A, Glidden, David V, Rodrigues, Warren C, Wang, Guohong, Vincent, Michael, Mugo, Nelly, Mujugira, Andrew, Marzinke, Mark, Hendrix, Craig, Gandhi, Monica, Celum, Connie, Coombs, Robert W, Lingappa, Jairam R, McElrath, M Juliana, Fife, Kenneth H, Were, Edwin, Tumwesigye, Elioda, Ndase, Patrick, Katabira, Elly, Ronald, Allan, Bukusi, Elizabeth, Cohen, Craig R, Wangisi, Jonathan, Campbell, James D, Tappero, Jordan W, Kiarie, James, Farquhar, Carey, John-Stewart, Grace, Mugo, Nelly R, and Ngure, Kenneth
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,HIV/AIDS ,Sexually Transmitted Infections ,Prevention ,Clinical Research ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Emtricitabine ,HIV ,HIV Infections ,Humans ,Immunoassay ,Medication Adherence ,Pre-Exposure Prophylaxis ,Tenofovir ,PrEP ,HIV prevention ,urine ,immunoassay ,ELISA ,Partners PrEP Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
New tools are needed to support PrEP adherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.
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- 2021
36. Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial
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DeJesus, Edwin, Richmond, Gary J., Berhe, Mezgebe, Ruane, Peter J., Sinclair, Gary Ian, Lichtenstein, Kenneth, Ramgopal, Moti N., Wiznia, Andrew, Workowski, Kimberly, Sanchez, William, Brinson, Cynthia, McGowan, Joseph P., Creticos, Catherine M., Berger, Daniel S., Wheeler, David A., Hagins, Debbie, Crofoot, Gordon E., Sims, James, Osiyemi, Olayemi, Hodge, Theo, Zurawski, Christine, Ogbuagu, Onyema, Segal-Maurer, Sorana, Ratanasuwan, Winai, Avihingsanon, Anchalee, Siripassorn, Krittaecho, Chetchotisakd, Ploenchan, Castagna, Antonella, Antinori, Andrea, Castelli, Francesco, Ronot-Bregigeon, Sylvie, Molina, Jean-Michel, Yazdanpanah, Yazdan, Trottier, Benoit, Brunetta, Jason, Shirasaka, Takuma, Yokomaku, Yoshiyuki, Koenig, Ellen, Mallolas, Josep, Stellbrink, Hans-Jurgen, Hung, Chien-Ching, Rassool, Mohammed, Wang, Hui, Margot, Nicolas, Dvory-Sobol, Hadas, Rhee, Martin S, and Baeten, Jared M
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- 2023
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37. Brief Report: Bacterial Vaginosis and Risk of HIV Infection in the Context of CD101 Gene Variation
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Wanga, Valentine, Mackelprang, Romel D, Thomas, Katherine K, Donnell, Deborah, Cohen, Craig R, Mugo, Nelly R, Bukusi, Elizabeth A, de Bruyn, Guy, Irungu, Elizabeth, Celum, Connie, Baeten, Jared M, and Lingappa, Jairam R
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Medical Microbiology ,Biomedical and Clinical Sciences ,Prevention ,Clinical Research ,Infectious Diseases ,Genetics ,HIV/AIDS ,Infection ,Adult ,Africa South of the Sahara ,Antigens ,CD ,Coinfection ,Female ,Genetic Predisposition to Disease ,Genetic Variation ,HIV Infections ,Humans ,Longitudinal Studies ,Male ,Membrane Glycoproteins ,Risk Factors ,Vaginosis ,Bacterial ,Young Adult ,BV ,CD101 ,inflammation ,HIV ,Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundWhether bacterial vaginosis (BV) and CD101 immunoglobulin-like (Ig-like) variants independently increase HIV risk through mucosal inflammation is not well understood. We evaluated whether the impact of BV on HIV acquisition in women differs by the presence or absence of candidate CD101 Ig-like variants.MethodsWe used data from 2 studies of HIV serodiscordant couples in east (Kenya, Tanzania, and Uganda) and southern (Botswana, South Africa, and Zambia) Africa, which longitudinally assessed HIV acquisition (by ELISA) and BV (by Nugent score ≥7). We used previously generated CD101 sequence data for each case and control participant to create a binary variable indicating the presence/absence of any of 5 CD101 Ig-like variants.ResultsConfirming previously shown results in this cohort, Ig-like variants increased HIV-infection risk (adjusted hazard ratio [aHR], = 2.63; 95% confidence interval [CI], 1.41 to 4.89). BV was associated with 2.5-fold higher HIV-infection risk only in the absence of Ig-like variants (aHR = 2.47; 95% CI, 0.99 to 6.15; P = 0.052), whereas in the presence of Ig-like variants, BV was not associated with higher HIV-infection risk (aHR = 0.87; 95% CI, 0.35 to 2.15; P = 0.765); however, a test for interaction was nonsignificant (P = 0.116).ConclusionsWe hypothesized that both BV and CD101 Ig-like variants facilitate HIV acquisition by augmenting similar genital inflammation pathways. Our findings indicate that inflammatory mucosal effects of Ig-like variants may influence the impact of BV on HIV risk. Host-defined inflammatory pathways may be useful targets for HIV prevention.
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- 2020
38. Women’s experience receiving drug feedback and adherence counseling in MTN-025/HOPE - an HIV Prevention open-label trial of the Dapivirine Vaginal Ring
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Katz, Ariana Wendy Keel, Balán, Iván C., Reddy, Krishnaveni, Etima, Juliane, Weber, Kubashni, Tauya, Thelma, Atujuna, Millicent, Scheckter, Rachel, Ngure, Kenneth, Soto-Torres, Lydia, Mgodi, Nyaradzo, Palanee-Phillips, Thesla, Baeten, Jared M., and van der Straten, Ariane
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- 2022
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39. Effects of the Waya Intervention on Marital Satisfaction and HIV Risk Behaviors in Western Kenya: A Pre–Post Study Design
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Kwena, Zachary Arochi, Bukusi, Elizabeth A., Turan, Janet M., Darbes, Lynae, Farquhar, Carey, Makokha, Catherine, and Baeten, Jared M.
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- 2022
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40. Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling
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Berard, Alicia R., Brubaker, Douglas K., Birse, Kenzie, Lamont, Alana, Mackelprang, Romel D., Noël-Romas, Laura, Perner, Michelle, Hou, Xuanlin, Irungu, Elizabeth, Mugo, Nelly, Knodel, Samantha, Muwonge, Timothy R., Katabira, Elly, Hughes, Sean M., Levy, Claire, Calienes, Fernanda L., Lauffenburger, Douglas A., Baeten, Jared M., Celum, Connie, Hladik, Florian, Lingappa, Jairam, and Burgener, Adam D.
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- 2023
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41. Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials
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Sax, Paul E., Arribas, José R., Orkin, Chloe, Lazzarin, Adriano, Pozniak, Anton, DeJesus, Edwin, Maggiolo, Franco, Stellbrink, Hans-Jürgen, Yazdanpanah, Yazdan, Acosta, Rima, Huang, Hailin, Hindman, Jason T., Martin, Hal, Baeten, Jared M., and Wohl, David
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- 2023
- Full Text
- View/download PDF
42. Defining gaps in pre-exposure prophylaxis delivery for pregnant and post-partum women in high-burden settings using an implementation science framework
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Pintye, Jillian, Davey, Dvora L Joseph, Wagner, Anjuli D, John-Stewart, Grace, Baggaley, Rachel, Bekker, Linda-Gail, Celum, Connie, Chi, Benjamin H, Coates, Thomas J, Groves, Allison K, Haberer, Jessica E, Heffron, Renee, Kinuthia, John, Matthews, Lynn T, McIntyre, James A, Moodley, Dhayendre, Mofenson, Lynne M, Mugo, Nelly, Mujugira, Andrew, Myer, Landon, Shoptaw, Steven, Stranix-Chibanda, Lynda, Baeten, Jared M, and Group, for the PrEP in Pregnancy Working
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Behavioral and Social Science ,Infectious Diseases ,Prevention ,Pediatric AIDS ,Clinical Research ,Pediatric ,HIV/AIDS ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Anti-HIV Agents ,Female ,HIV Infections ,Health Plan Implementation ,Humans ,Infectious Disease Transmission ,Vertical ,Male ,Postnatal Care ,Pre-Exposure Prophylaxis ,Pregnancy ,PrEP in Pregnancy Working Group ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context.
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- 2020
43. Brief Report: High Accuracy of a Real-Time Urine Antibody-Based Tenofovir Point-of-Care Test Compared With Laboratory-Based ELISA in Diverse Populations.
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Spinelli, Matthew A, Rodrigues, Warren C, Wang, Guohong, Vincent, Michael, Glidden, David V, Okochi, Hideaki, Stalter, Randy, Defechereux, Patricia, Deutsch, Madeline, Grant, Robert M, Ngure, Kenneth, Mugo, Nelly R, Baeten, Jared M, and Gandhi, Monica
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Antibodies ,Drug Combinations ,Drug Monitoring ,Emtricitabine ,Enzyme-Linked Immunosorbent Assay ,Female ,HIV Infections ,Humans ,Kenya ,Laboratories ,Male ,Patient Compliance ,Point-of-Care Testing ,Sensitivity and Specificity ,Tenofovir ,Uganda ,pre-exposure prophylaxis ,point-of-care ,adherence ,real-time ,antiretroviral therapy ,Partners PrEP Study Team ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundTherapeutic drug monitoring measures antiretroviral adherence more accurately than self-report but has not been available at the point-of-care (POC) until now. We compare a novel POC test for urine tenofovir to laboratory-based enzyme-linked immunosorbent assay (ELISA) testing in diverse patient populations urine pre-exposure prophylaxis (PrEP).SettingUrine samples were analyzed using ELISA and the POC lateral flow immunoassay (LFA) test from 2 cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited Kenyan and Ugandan heterosexual men and women, and the IBrEATHe Study, which recruited US transgender women and men using gender-affirming hormone therapy.MethodsWe calculated the sensitivity, specificity, and accuracy of the POC test compared with ELISA at a cutoff of 1500 ng/mL.ResultsOverall, 684 urine samples were tested from 324 participants in the 2 cohorts. In Partners PrEP, 454 samples from 278 participants (41% women) were tested with a median age of 33 years. In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested with a median age of 31 years. Comparison of the LFA read-out to ELISA yielded 100% sensitivity [97.5% one-sided confidence interval (CI) = 99.3%], 98.3% specificity (95% CI = 95.2% to 99.7%), and 99.6% accuracy (95% CI = 98.7% to 99.9%).ConclusionThe sensitivity, specificity, and accuracy of a novel POC test for urine tenofovir all exceeded 98% when compared with a laboratory-based ELISA method when tested in diverse patient populations. Given the LFA's high accuracy and expected low cost, this POC test is a promising tool to support antiretroviral adherence that could be widely scalable to real-world clinical settings.
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- 2020
44. Urine Tenofovir Concentrations Correlate With Plasma and Relate to Tenofovir Disoproxil Fumarate Adherence: A Randomized, Directly Observed Pharmacokinetic Trial (TARGET Study)
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Drain, Paul K, Kubiak, Rachel W, Siriprakaisil, Oraphan, Klinbuayaem, Virat, Quame-Amaglo, Justice, Sukrakanchana, Pra-Ornsuda, Tanasri, Suriyan, Punyati, Pimpinun, Sirirungsi, Wasna, Cressey, Ratchada, Bacchetti, Peter, Okochi, Hideaki, Baeten, Jared M, Gandhi, Monica, and Cressey, Tim R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Emtricitabine ,HIV Infections ,Humans ,Male ,Pharmaceutical Preparations ,Plasma ,Pre-Exposure Prophylaxis ,Tenofovir ,HIV ,preexposure prophylaxis ,antiretroviral treatment ,tenofovir ,directly observed therapy ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundDirect measurement of tenofovir (TFV) in urine could be an objective measure to monitor adherence to preexposure prophylaxis (PrEP) or TFV-based antiretroviral therapy (ART).MethodsWe conducted a 3-arm randomized, pharmacokinetic study of tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg among adults living with human immunodeficiency virus. Participants were randomized to receive controlled TDF/FTC dosing as (1) "perfect" adherence (daily); (2) "moderate" adherence (4 doses/week); or (3) "low" adherence (2 doses/week). We obtained trough spot urine and plasma samples during a 6-week directly observed therapy period and a 4-week washout period. TFV concentrations were compared between adherence arms using 1-way analysis of variance.ResultsAmong 28 participants, the median age was 33 years and 16 (57%) were male. Correlation between TFV plasma and urine concentrations was strong (ρ = 0.78; P < .0001). Median (interquartile range) steady-state trough TFV concentrations (ng/mL) for perfect, moderate, and low TDF adherence were 41 (26-52), 16 (14-19), and 4 (3-5) in plasma; and 6480 (3940-14 300), 3405 (2210-5020), and 448 (228-675) in urine. Trough TFV concentrations at steady state were significantly different between the 3 adherence arms for plasma (P < .0001) and urine (P = .0002). Following drug cessation, TFV concentrations persisted longer in urine than plasma samples. Washout urine TFV concentrations and time to undetectable concentrations did not differ between the 3 randomized adherence groups.ConclusionsUrine TFV concentrations can inform interpretation of novel point-of-care urine-based TFV assays to assess recent TDF adherence.Clinical trials registrationNCT03012607
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- 2020
45. Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.
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Reddy, Krishnaveni, Kelly, Cliff, Brown, Elizabeth R, Jeenarain, Nitesha, Naidoo, Logashvari, Siva, Samantha, Bekker, Linda-Gail, Nair, Gonasagrie, Makanani, Bonus, Chinula, Lameck, Mgodi, Nyaradzo, Chirenje, Zvavahera, Kiweewa, Flavia Matovu, Marrazzo, Jeanne, Bunge, Katherine, Soto-Torres, Lydia, Piper, Jeanna, Baeten, Jared M, and Palanee-Phillips, Thesla
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Topical Microbicides ,Prevention ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Anti-HIV Agents ,Contraceptive Devices ,Female ,Double-Blind Method ,Female ,HIV Infections ,HIV Seropositivity ,HIV-1 ,Humans ,Pyrimidines ,Vagina ,Young Adult ,cytology ,dapivirine ,preexposure prophylaxis ,vaginal ring ,MTN-020/ASPIRE and MTN-003/VOICE Study Teams ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveWe aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities.DesignSecondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE).MethodsData from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population.ResultsCervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24).ConclusionThese findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.
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- 2020
46. Development and validation of the first point-of-care assay to objectively monitor adherence to HIV treatment and prevention in real-time in routine settings.
- Author
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Gandhi, Monica, Wang, Guohong, King, Roger, Rodrigues, Warren C, Vincent, Michael, Glidden, David V, Cressey, Tim R, Bacchetti, Peter, Spinelli, Matthew A, Okochi, Hideaki, Siriprakaisil, Oraphan, Klinbuayaem, Virat, Mugo, Nelly R, Ngure, Kenneth, Drain, Paul K, and Baeten, Jared M
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Biomedical and Clinical Sciences ,Sexually Transmitted Infections ,HIV/AIDS ,Bioengineering ,Clinical Research ,Clinical Trials and Supportive Activities ,Prevention ,Infectious Diseases ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Chromatography ,Liquid ,Gold ,HIV Infections ,Humans ,Medication Adherence ,Metal Nanoparticles ,Point-of-Care Testing ,Pre-Exposure Prophylaxis ,Tandem Mass Spectrometry ,Tenofovir ,adherence ,antiretroviral treatment ,lateral flow assay ,point-of-care ,preexposure prophylaxis ,tenofovir ,urine ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveHIV prevention and treatment studies demonstrate that pharmacologic adherence metrics are more accurate than self-report. Currently available metrics use liquid-chromatography/tandem-mass-spectrometry (LC-MS/MS), which is expensive and laboratory-based. We developed a specific and sensitive antibody against tenofovir, the backbone of treatment and prevention, but conversion to a lateral flow assay (LFA) - analogous to a urine pregnancy test - is required for point-of-care testing. We describe the development of the first LFA to measure antiretroviral adherence in real-time.MethodsPrevious work in a directly observed therapy study of providing tenofovir disoproxil fumarate (TDF) to HIV-noninfected volunteers at various simulated adherence patterns defined the appropriate cut-off for the LFA (1500 ng tenofovir/ml urine). We developed the LFA using a sample pad for urine; a conjugate pad coated with TFV-specific antibodies conjugated to colloidal gold nanoparticles; a nitrocellulose membrane striped with tenofovir-antigen (test line) and a control line; with an absorbent pad to draw urine across the reaction membrane.ResultsWe tested 300 urine samples collected from the directly observed therapy study by this LFA and the gold-standard method of LC-MS/MS. The LFA demonstrated 97% specificity (95% CI 93-99%) and 99% sensitivity (94-100%) compared with LC-MS/MS. The LFA accurately classified 98% of patients who took a dose within 24 h as adherent.ConclusionWe describe the development and validation of the first point-of-care assay to measure short-term adherence to HIV prevention and treatment in routine settings. The assay is low-cost, easy-to-perform and measures the breakdown product (tenofovir) of both TDF and tenofovir alafenamide (TAF). This assay has the potential to improve HIV and PrEP outcomes worldwide by triggering differentiated service delivery with further study merited.
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- 2020
47. Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?
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Joseph Davey, Dvora L, Pintye, Jillian, Baeten, Jared M, Aldrovandi, Grace, Baggaley, Rachel, Bekker, Linda-Gail, Celum, Connie, Chi, Benjamin H, Coates, Thomas J, Haberer, Jessica E, Heffron, Renee, Kinuthia, John, Matthews, Lynn T, McIntyre, James, Moodley, Dhayendre, Mofenson, Lynne M, Mugo, Nelly, Myer, Landon, Mujugira, Andrew, Shoptaw, Steven, Stranix-Chibanda, Lynda, John-Stewart, Grace, and PrEP in Pregnancy Working Group
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PrEP in Pregnancy Working Group ,Humans ,HIV-1 ,Pregnancy Complications ,Infectious ,HIV Infections ,Anti-HIV Agents ,Postnatal Care ,Breast Feeding ,Pregnancy ,Adult ,Female ,Young Adult ,Pre-Exposure Prophylaxis ,Tenofovir ,HIV ,PMTCT ,PrEP ,breastfeeding ,preexposure prophylaxis ,pregnancy ,prevention of mother to child transmission ,Pregnancy Complications ,Infectious ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Abstract
IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.
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- 2020
48. Emerging evidence from a systematic review of safety of pre‐exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?
- Author
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Davey, Dvora L Joseph, Pintye, Jillian, Baeten, Jared M, Aldrovandi, Grace, Baggaley, Rachel, Bekker, Linda‐Gail, Celum, Connie, H, Benjamin, Coates, Thomas J, Haberer, Jessica E, Heffron, Renee, Kinuthia, John, Matthews, Lynn T, McIntyre, James, Moodley, Dhayendre, Mofenson, Lynne M, Mugo, Nelly, Myer, Landon, Mujugira, Andrew, Shoptaw, Steven, Stranix‐Chibanda, Lynda, John‐Stewart, Grace, and Group, for the PrEP in Pregnancy Working
- Subjects
Biomedical and Clinical Sciences ,Midwifery ,Public Health ,Health Sciences ,Reproductive Medicine ,Breastfeeding ,Lactation and Breast Milk ,HIV/AIDS ,Sexually Transmitted Infections ,Prevention ,Pregnancy ,Maternal Health ,Infectious Diseases ,Maternal Morbidity and Mortality ,Pediatric ,Women's Health ,Perinatal Period - Conditions Originating in Perinatal Period ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Breast Feeding ,Female ,HIV Infections ,HIV-1 ,Humans ,Postnatal Care ,Pre-Exposure Prophylaxis ,Pregnancy Complications ,Infectious ,Tenofovir ,Young Adult ,preexposure prophylaxis ,PrEP ,pregnancy ,breastfeeding ,PMTCT ,prevention of mother to child transmission ,HIV ,PrEP in Pregnancy Working Group ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.
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- 2020
49. Social harms in female-initiated HIV prevention method research: state of the evidence.
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Montgomery, Elizabeth T, Roberts, Sarah T, Nel, Annalene, Malherbe, Mariette, Torjesen, Kristine, Bunge, Katherine, Singh, Devika, Baeten, Jared M, Marrazzo, Jeanne, Chirenje, Z Mike, Kabwigu, Samuel, Beigi, Richard, Riddler, Sharon A, Gaffour, Zakir, Reddy, Krishnaveni, Mansoor, Leila E, Nair, Gonasagrie, Woeber, Kusbashni, Moodley, Jayajothi, Jeenarain, Nitesha, Siva, Samantha, Naidoo, Logashvari, Govender, Vaneshree, and Palanee-Phillips, Thesla
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Biomedical and Clinical Sciences ,Health Services and Systems ,Public Health ,Health Sciences ,Clinical Sciences ,Topical Microbicides ,Behavioral and Social Science ,HIV/AIDS ,Prevention ,Clinical Research ,Infectious Diseases ,Mental Health ,Patient Safety ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Africa South of the Sahara ,Anti-HIV Agents ,Double-Blind Method ,Ethics ,Research ,Female ,HIV Infections ,Humans ,Intimate Partner Violence ,Male ,Patient Participation ,Prospective Studies ,Safety ,Vaginal Creams ,Foams ,and Jellies ,Africa ,HIV ,microbicide ,social harms ,women ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectivesAssessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for 'social harms', generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on social harms within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts.MethodsSecondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials.ResultsSocial harms reporting was low across the largest and most recent microbicide studies. Social harm incidence per 100 person-years ranged from 1.10 (95% CI 0.78-1.52) to 3.25 (95% CI 2.83-3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. Social harms were most frequently associated with male partners, rather than, for example, experiences of stigma in the community.ConclusionMeasurement and screening for social harms is an important component of conducting ethical research of novel HIV prevention methods. To date, social harm incidence reported in microbicide trials has been relatively low (
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- 2019
50. A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda.
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Patel, Rena C, Stalter, Randy M, Thomas, Katherine K, Tamraz, Bani, Blue, Steven W, Erikson, David W, Kim, Christina J, Kelly, Edward J, Nanda, Kavita, Kourtis, Athena P, Lingappa, Jairam R, Mugo, Nelly, Baeten, Jared M, and Scarsi, Kimberly K
- Subjects
Genetics ,Clinical Research ,Contraception/Reproduction ,Patient Safety ,HIV/AIDS ,Infectious Diseases ,Good Health and Well Being ,Adult ,Alkynes ,Anti-HIV Agents ,Benzoxazines ,Contraceptive Agents ,Female ,Cyclopropanes ,Desogestrel ,Drug Antagonism ,Female ,HIV Infections ,Humans ,Kenya ,Levonorgestrel ,Linear Models ,Nevirapine ,Pharmacogenomic Testing ,Uganda ,antiretroviral therapy ,efavirenz ,etonogestrel ,hormonal contraception ,implants ,levonorgestrel ,pharmacogenetic ,pharmacokinetic ,Partners PrEP Study Team ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology - Abstract
ObjectivesTo evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz (EFV)-containing or nevirapine (NVP)-containing antiretroviral therapy (ART).DesignWe analyzed stored samples from women self-reporting implant use in the Partners PrEP Study.MethodsPlasma samples collected every 6 months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from samples collected after ART initiation were compared with pre-ART concentrations for intraindividual comparisons. We used adjusted linear mixed models to compare hormone concentrations between individuals on EFV and NVP to a no ART group. We then evaluated whether possessing certain alleles with known or possible influences on EFV, NVP, or progestin metabolism were associated with changes in progestin concentrations or modified the association between ART use and progestin concentrations.ResultsOur analysis included 11 women who initiated EFV, 13 who initiated NVP, and 36 who remained ART-naive. In the EFV group, the adjusted geometric mean ratio (aGMR) of levonorgestrel was 0.39 [90% confidence intervals (0.31, 0.49); P
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- 2019
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