NRU :: Browsing by Author "Baeten, Jared M."

Browsing by Author "Baeten, Jared M."

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Acceptability and use of a dapivirine vaginal ring in a phase III trial
(AIDS (London, England), 2017) Montgomery, Elizabeth T.; Straten, Ariane van der; Chitukuta, Miria; Reddy, Krishnaveni; Woeber, Kubashni; Atujuna, Millicent; Bekker, Linda-Gail; Etima, Juliane; Nakyanzi, Teopista; Mayo, Ashley J.; Katz, Ariana; Laborde, Nicole; Grossman, Cynthia I.; Soto-Torres, Lydia; Palanee-Phillips, Thesla; Baeten, Jared M.
The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. Method—Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. Results—We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. Conclusion—It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden.
Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples
(Journal of the International AIDS Society, 2019) Nakku-Joloba, Edith; Pisarski, Emily E.; Wyatt, Monique A.; Muwonge, Timothy R.; Asiimwe, Stephen; Celum, Connie L.; Baeten, Jared M.; Katabira, Elly T.; Ware, Norma C.
Pre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users. Methods: The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a “bridge” to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results: Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples’ sense of protection against HIV infection and raising the prospect of a return to “live sex” (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions: The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.
Comparison of short messaging service self-reported adherence with other adherence measures in a demonstration project of HIV preexposure prophylaxis in Kenya and Uganda
(AIDS (London, England), 2018) Musinguzi, Nicholas; Muwonge, Timothy; Ngure, Kenneth; Katabira, Elly; Mugo, Nelly; O’Rourke Burns, Bridget Frances; Baeten, Jared M.; Heffron, Renee; Haberer, Jessica E.
Short messaging service (SMS) can collect adherence data on a frequent basis and is relatively anonymous, and therefore could potentially reduce recall and social desirability biases prevalent in other self-reported measures. Methods: We compared SMS self-reported adherence with three self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and two objective adherence measures [electronic adherence monitoring (EAM) and plasma tenofovir levels] using data from HIV-uninfected members of serodiscordant couples enrolled in a preexposure prophylaxis demonstration project in Kenya and Uganda. Results: Of 373 enrolled participants, 256 (69%) were male and median age at enrolment was 29 years (26, 35). Fifty-two percent were from Kenya and median education at enrolment was 10 years (7,12). Overall, median adherence was 90, 75, 85,94 and 79%, respectively, for self-report by SMS, rating, frequency, percentage and EAM adherence. Spearman’s correlation coefficient between SMS and interviewer- administered self-reported measures was 0.18 for rating and frequency, 0.22 for percentage and 0.14 for EAM (all P< 0.001). The estimated difference in average adherence between SMS and self-reported rating, frequency, percentage adherence and EAM was 8.1 (P < 0.001), 0.3 (P = 0.81), −5.2 (P < 0.001) and 9.5 (P < 0.001), respectively. Area under the receiver-operating curve assessing the ability of SMS self-report to discriminate between detectable and undetectable tenofovir was 0.51. Conclusion: Our study found low correlation between SMS self-report and other self-reported and objective adherence measures and did not discriminate between detectable and undetectable plasma tenofovir levels. Future use of SMS self-report should explore alternative means for reducing potential biases.
Context matters: PrEP adherence is associated with sexual behavior among HIV serodiscordant couples in East Africa
(Journal of acquired immune deficiency syndromes, 2017) Haberer, Jessica E.; Ngure, Kenneth; Muwonge, Timothy; Mugo, Nelly; Katabira, Elly; Heffron, Renee; Musinguzi, Nicholas; Bangsberg, David R.; Celum, Connie; Baeten, Jared M.
Short message service (SMS) surveys are a promising tool for understanding whether pre-exposure prophylaxis (PrEP) adherence aligns with risk for HIV acquisition— a concept known as prevention-effective adherence. Methods—The Partners Demonstration Project was an open-label study of integrated PrEP and antiretroviral therapy (ART) delivery among high-risk HIV serodiscordant couples in East Africa. HIV-uninfected partners were offered PrEP until their HIV-infected partner had taken ART for ≥6 months. At 2 study sites, HIV-uninfected partners were offered enrollment into the Partners Mobile Adherence to PrEP (PMAP) sub-study based on ongoing PrEP use, personal cell phone ownership, and ability to use SMS. SMS surveys asked about PrEP adherence and sexual activity in the prior 24 hours; these surveys were sent daily for the 7 days prior and 7 days after routine study visits in the Partners Demonstration Project. Results—The PMAP sub-study enrolled 373 HIV-uninfected partners; 69% were male and mean age was 31 years. Participants completed 17,030 of 23,056 SMS surveys sent (74%) with a mean of 47 surveys per participant over 9.8 months of follow-up. While HIV-infected partner use of ART was <6 months, mean reported PrEP adherence was 92% on surveys concurrently reporting sex within the serodiscordant partnership and 84% on surveys reporting no sex (p<0.001). Discussion—SMS surveys provided daily assessment of concurrent PrEP adherence and sexual behavior. Higher PrEP adherence was temporally associated with increased risk for HIV acquisition.
Dapivirine vaginal ring use does not diminish the effectiveness of hormonal contraception
(Journal of acquired immune deficiency syndromes, 2017) Balkus, Jennifer E.; Palanee-Phillips, Thesla; Reddy, Krishnaveni; Siva, Samantha; Harkoo, Ishana; Nakabiito, Clemensia; Kintu, Kenneth; Nair, Gonasangrie; Chappell, Catherine; Matovu Kiweewa, Flavia; Kabwigu, Samuel; Naidoo, Logashvari; Jeenarain, Nitesha; Marzinke, Mark; Soto-Torres, Lydia; Brown, Elizabeth R.; Baeten, Jared M.
To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use. A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention. Methods: Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection. Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm, 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods. Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially due to poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.
Does Adherence Change When No One is Looking? Comparing Announced and Unannounced Tenofovir Levels in a PrEP Trial
(Journal of acquired immune deficiency syndromes, 2017) Musinguzi, Nicholas; Muwonge, Timothy; Thomas, Katherine; Baeten, Jared M.; Bangsberg, David R.; Haberer, Jessica E.
Differences between unannounced and announced tenofovir levels as measures of PrEP adherence are not well understood. In an ancillary adherence study involving one urban site (Kampala) and two rural sites (Kabwohe and Tororo) from the Partners PrEP study, 268 specimen pairs from chronologically proximal clinic and home visits were tested for plasma tenofovir levels. Comparing clinic and home specimens, 89 versus 89 % were classified as detectable ([0.31 ng/ml; p = 0.77), 87 versus 86 % as recent dosing ([10 ng/ml; p = 0.80), and 82 versus 80 % as steady-state ([40 ng/ml; p = 0.44). Mean difference between announced and unannounced drug levels, adjusted for specimen collection time was 3.2 ng/ml (p = 0.50) for Kabwohe, 23.2 ng/ml (p = 0.003) for Kampala and -3.3 ng/ml p = 0.69) for Tororo. In the setting of high adherence, plasma tenofovir levels tested at the clinic were categorically similar as levels tested at home; however, differences were seen between urban and rural settings.
Effect of HIV Self-Testing on PrEP Adherence Among Gender-Diverse Sex Workers in Uganda: A Randomized Trial
(Journal of acquired immune deficiency syndromes, 2022) Mujugira, Andrew; Nakyanzi, Agnes; Nabaggala, Maria S.; Muwonge, Timothy R.; Ssebuliba, Timothy; Bagaya, Monica; Nampewo, Olivia; Sapiri, Oliver; Nyanzi, Kikulwe R.; Bambia, Felix; Nsubuga, Rogers; Serwadda, David M.; Ware, Norma C.; Baeten, Jared M.; Haberer, Jessica E.
HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) are complementary tools that could empower sex workers to control their HIV protection, but few studies have jointly evaluated PrEP and HIVST in any setting. Methods: The Empower Study was an open-label randomized trial in Uganda. Sex workers were offered F/tenofovir disoproxil fumarate and randomized 1:1 to monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard of care) and followed up for 12 months. PrEP adherence was measured using electronic adherence monitoring and tenofovir diphosphate (TFV-DP) levels in dried blood spots. Adherence outcomes and sexual behaviors were compared by arm using generalized estimating equation models. Results: We enrolled 110 sex workers: 84 cisgender women, 14 transgender women, 10 men who have sex with men, and 2 transgender men. The median age was 23 years. The 12-month retention was 75%. Nearly all (99.4%) used $1 HIVST kit. The proportion with TFV-DP levels $700 fmol/punch in the HIVST and standard of care arms at the 3-, 6-, 9-, and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (P . 0.2). Self-reported condomless sex acts with paying partners was similar by arm [adjusted incidence rate ratio 0.70; 95% confidence interval (CI): 0.42 to 1.17; P = 0.18]. One seroconversion occurred (HIV incidence, 0.9/100 person-years); TFV-DP was not detected at any visit. Conclusions: A gender-diverse sample of sex workers in Uganda used HIVST but not daily oral PrEP for HIV protection. Alternate approaches to promote PrEP use, including long-acting formulations, should be considered in this population.
Health Care Worker Perspectives of HIV Pre-exposure Prophylaxis Service Delivery in Central Uganda
(Frontiers in Public Health, 2022) Muwonge, Timothy R.; Nsubuga, Rogers; Ware, Norma C.; Wyatt, Monique A.; Pisarski, Emily; Kamusiime, Brenda; Kasiita, Vicent; Kakoola Nalukwago, Grace; Brown, Charles; Nakyanzi, Agnes; Bagaya, Monica; Bambia, Felix; Ssebuliba, Timothy; Katabira, Elly; Kyambadde, Peter; Baeten, Jared M.; Heffron, Renee; Celum, Connie; Mujugira, Andrew; Haberer, Jessica E.
Scale-up of HIV pre-exposure prophylaxis (PrEP) services in Uganda is ongoing. However, health care workers (HCWs) may not be aware of PrEP nor what offering this service entails. We explored the impact of standardized HCW training on the knowledge and perspectives of PrEP service delivery in Uganda. Methods: We recruited HCWs from facilities that offered HIV-related services in Central Uganda. Using the Uganda Ministry of Health curriculum, we trained HCWs on PrEP services. We collected data about PrEP knowledge, preparedness, and willingness to deliver PrEP to multiple key populations before the training, immediately after the training, and >6 months later (exit). We additionally conducted 15 qualitative interviews after the exit survey. Quantitative data were analyzed by Fisher exact test, while qualitative interview data were analyzed inductively. Results: We recruited 80 HCWs from 35 facilities in urban (N = 24, 30%), peri-urban (N = 30, 37%), and rural (N = 26, 33%) areas. Most HCWs were nurse counselors (N = 52, 65%) or medical/clinical officers (N = 15, 18%). Surveys indicated that awareness of PrEP increased after the training and remained high. Knowledge of PrEP (i.e., as an effective, short-term antiretroviral medication to use before HIV exposure for people at high risk) generally increased with training, but significant gaps remained, and knowledge decreased with time. Most HCWs recommended PrEP for female sex workers and HIV serodifferent couples, as well as other key populations. We observed increases in the number of HCW who felt their facility was prepared to cater for HIV prevention and provide PrEP, but this view was not universal. HCWs believed in PrEP effectiveness and embraced it as an additional HIV prevention method. Concerns included patient adherence and behavioral risk compensation. HCWs noted challenges in PrEP delivery in terms of inadequate clinic preparedness, infrastructure, staff capacity, and poor attitudes toward key populations by untrained health workers. They felt further training was needed to ensure a smooth scale-up of services without stigmatization. Standardized training improved knowledge, willingness, and preparedness to offer PrEP services among most HCWs in Central Uganda. Ongoing training will be needed to optimize PrEP delivery services and expand delivery to levels needed for population-level impact.
HIV self-testing and oral pre-exposure prophylaxis are empowering for sex workers and their intimate partners: a qualitative study in Uganda
(Journal of the International AIDS Society, 2021) Mujugira, Andrew; Nakyanzi, Agnes; Kasiita, Vicent; Kamusiime, Brenda; Nalukwago, Grace K.; Nalumansi, Alisaati; Twesigye, Chris C.; Muwonge, Timothy R.; Baeten, Jared M.; Wyatt, Monique A.; Haberer, Jessica E.; Ware, Norma C.
HIV self-testing (HIVST) and oral pre-exposure prophylaxis (PrEP) are complementary, evidence-based, selfcontrolled HIV prevention tools that may be particularly appealing to sex workers. Understanding how HIVST and PrEP are perceived and used by sex workers and their intimate partners could inform prevention delivery for this population. We conducted qualitative interviews to examine ways in which HIVST and PrEP use influence prevention choices among sex workers in Uganda. Methods: Within a randomized trial of HIVST and PrEP among 110 HIV-negative cisgender women, cisgender men and transgender women sex workers (NCT03426670), we conducted 40 qualitative interviews with 30 sex workers and 10 intimate partners (June 2018 to January 2020). Sex worker interviews explored (a) experiences of using HIVST kits; (b) how HIVST was performed with sexual partners; (c) impact of HIVST on PrEP pill taking; and (d) sexual risk behaviours after HIVST. Partner interviews covered (i) introduction of HIVST; (ii) experiences of using HIVST; (iii) HIV status disclosure; and (iv) HIVST’s effect on sexual behaviours. Data were analysed using an inductive content analytic approach centering on descriptive category development. Together, these categories detail the meaning of HIVST and PrEP for these qualitative participants. Results: Using HIVST and PrEP was empowering for this group of sex workers and their partners. Three types of empowerment were observed: (a) economic; (b) relational; and (c) sexual health. (i) Using HIVST and PrEP made sex without condoms safer. Sex workers could charge more for condomless sex, which was empowering economically. (ii) Self-testing restored trust in partners’ fidelity upon being reunited after a separation. This trust, in combination with condomless sex made possible by PrEP use, restored intimacy, empowering partnered relationships. (iii) HIVST and PrEP enabled sex workers to take control of their HIV prevention efforts and avoid the stigma of public clinic visits. In this way they were empowered to protect their sexual health. Conclusions: In this sample, sex workers’ use of HIVST and PrEP benefitted not only prevention efforts, but also economic and relational empowerment. Understanding these larger benefits and communicating them to stakeholders could strengthen uptake and use of combination prevention interventions in this marginalized population.
HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV- 1-Exposed Seronegative Women on Oral Preexposure Prophylaxis
(Journal of virology, 2016) Lund, Jennifer M.; Broliden, Kristina; Pyra, Maria N.; Thomas, Katherine K.; Donnell, Deborah; Irungu, Elizabeth; Muwonge, Timothy R.; Mugo, Nelly; Manohar, Madhuri; Jansson, Marianne; Mackelprang, Romel; Marzinke, Mark A.; Baeten, Jared M.; Lingappa, Jairam R.
Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P 0.008). Using a cutoff of>90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.
Household-Based HIV Counseling and Testing as a Platform for Referral to HIV Care and Medical Male Circumcision in Uganda: A Pilot Evaluation
(PloS one, 2012) Tumwebaze, Henry; Tumwesigye, Elioda; Baeten, Jared M.; Kurth, Ann E.; Revall, Jennifer; Murnane, Pamela M.; Chang, Larry W.; Celum, Connie
Combination HIV prevention initiatives incorporate evidence-based, biomedical and behavioral interventions appropriate and acceptable to specific populations, aiming to significantly reduce population-level HIV incidence. Knowledge of HIV serostatus is key to linkages to HIV care and prevention. Household-based HIV counseling and testing (HBCT) can achieve high HIV testing rates. We evaluated HBCT as a platform for delivery of combination HIV prevention services in sub-Saharan Africa. Methods: We conducted HBCT in a semi-urban area in southwestern Uganda. All adults received standard HIV prevention messaging. Real-time electronic data collection included a brief risk assessment and prevention triage algorithm for referrals of HIV seropositive persons to HIV care and uncircumcised HIV seronegative men with multiple sex partners to male circumcision. Monthly follow-up visits for 3 months were conducted to promote uptake of HIV care and male circumcision. Results: 855 households received HBCT; 1587 of 1941 (81.8%) adults were present at the HBCT visit, 1557 (98.1% of those present) were tested and received HIV results, of whom, 46.5% were men. A total of 152 (9.8%) were HIV seropositive, for whom the median CD4 count was 456 cells/mL, and 50.7% were newly-identified as HIV seropositive. Three months after HBCT, 88.5% of HIV seropositive persons had attended an HIV care clinic; among those with CD4 counts ,250 cells/mL, 71.4% initiated antiretroviral therapy. Among 123 HIV seronegative men with an HIV+ partner or multiple partners, 62.0% were circumcised by month 3. Conclusions: HBCT achieves high levels of knowledge of HIV serostatus and is an effective platform for identifying at-risk persons and achieving higher uptake of HIV prevention and care services through referrals and targeted follow-up than has been accomplished through other single focus strategies.
Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study
(BMC public health, 2021) Garcia, Morgan; Luecke, Ellen; Mayo, Ashley J.; Scheckter, Rachel; Ndase, Patrick; Matovu Kiweewa, Flavia; Kemigisha, Doreen; Musara, Petina; Singh, Nishanta; Palanee-Phillips, Thesla; Baeten, Jared M.; Torjesen, Kristine; Mansoor, Leila E.
Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebocontrolled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. Methods: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. Results: 2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p <0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52).
The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study
(Critical care medicine, 2012) Jacob, Shevin T; Banura, Patrick; Baeten, Jared M.; Moore, Christopher C.; Meya, David; Nakiyingi, Lydia; Burke, Rebecca; Horton, Cheryl Lynn; Iga, Boaz; Mayanja-Kizza, Harriet; for the Promoting Resource-Limited Interventions for Sepsis Management in Uganda (PRISM-U) Study Group The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study
In sub-Saharan Africa, sepsis is an important cause of mortality but optimal sepsis management including fluid resuscitation, early antibiotic administration and patient monitoring is limited by a lack of supplies and skilled health workers.To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda.A prospective before and after study of an intervention cohort (n=426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n=245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals.Early sepsis management provided by a dedicated study medical officer comprised of fluid resuscitation, early antibiotics and regular monitoring in the first 6 hours of hospitalization.Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006).The majority (86%) of patients in both cohorts were HIV-infected. Median fluid volume provided in the first 6 hours of hospitalization was higher in intervention than observation cohort patients (3000 vs. 500 mL, p<0.001) and a greater proportion of intervention cohort patients received antibacterial therapy in less than one hour (67% vs 30.4%, p<0.001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs 45.7%, log-rank p=0.005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted HR=0.74, 95% CI=0.55–0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered.Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital.
Impact of Male Partner Involvement on Women’s Adherence to the Dapivirine Vaginal Ring During a Phase III HIV Prevention Trial
(AIDS and Behavior, 2020) Roberts, Sarah T.; Nair, Gonasagrie; Baeten, Jared M.; Palanee‑Philips, Thesla; Schwartz, Katie; Reddy, Krishnaveni; Kabwigu, Samuel; Matovu Kiweewa, Flavia; Govender, Vaneshree; Gaffoor, Zakir; Singh, Nishanta; Siva, Samantha; Naidoo, Kalendri; Montgomery, Elizabeth T.
identified as one of the most significant factors impacting women’s willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women’s adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64–80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03–1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38–35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70–6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36–10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.
Impact of the Dapivirine Vaginal Ring on Sexual Experiences and Intimate Partnerships of Women in an HIV Prevention Clinical Trial: Managing Ring Detection and Hot Sex
(AIDS and Behavior, 2018) Laborde, Nicole D.; Pleasants, Elizabeth; Reddy, Krishnaveni; Atujuna, Millicent; Nakyanzi, Teopista; Chitukuta, Miria; Naidoo, Sarita; Palanee-Phillips, Thesla; Baeten, Jared M.; Montgomery, Elizabeth T.
Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants’ sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners’ interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners’ discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves
Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1 serodiscordant couples in East Africa: a qualitative evaluation study in Uganda
(Journal of the International AIDS Society, 2018) Ware, Norma C.; Pisarski, Emily E.; Nakku-Joloba, Edith; Wyatt, Monique A.; Muwonge, Timothy R.; Turyameeba, Bosco; Asiimwe, Stephen B.; Heffron, Renee A.; Baeten, Jared M.; Celum, Connie L.; Katabira, Elly T.
Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. Methods: Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples’ experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain “why the integrated strategy worked.” Results: Couples found “couples-focused” services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for “getting help” to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a “couples orientation” to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. Conclusions: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples’ experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out.
Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score
(PloS one, 2013) Jacob, Shevin T.; Pavlinac, Patricia B.; Nakiyingi, Lydia; Banura, Patrick; Baeten, Jared M.; Morgan, Karen; Magaret, Amalia; Manabe, Yuka; Reynolds, Steven J.; Liles, W. Conrad; Wald, Anna; Joloba, Moses L.; Mayanja-Kizza, Harriet; Michael Scheld, W.
When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.
Pre-exposure prophylaxis differentially alters circulating and mucosal immune cell activation in HSV-2 seropositive women
(AIDS (London, England), 2019) Richert-Spuhler, Laura E.; Pattacini, Laura; Plews, Margot; Irungu, Elizabeth; Muwonge, Timothy R.; Katabira, Elly; Mugo, Nelly; Meyers, Adrienne F.A.; Celum, Connie; Baeten, Jared M.; Lingappa, Jairam R.; Lund, Jennifer M.
Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an important tool for prevention of new HIV infections, which also reduces subclinical HSV-2 shedding and symptomatic lesions in HIV-negative, HSV-2-seropositive individuals. However, the impact of PrEP on mucosal immunity has not been examined in detail. Design: Here we evaluate paired genital tissue and systemic immune profiles to characterize the immunological effects of PrEP in HIV-negative, HSV-2-seropositive African women sexually exposed to HIV. Methods: We compared local and systemic innate and T-cell characteristics in samples collected during PrEP usage and two months after PrEP discontinuation. Results: We found that frequencies of cervical CCR5+CD4+ cells, regulatory T-cells, and tissue macrophages were significantly reduced during PrEP use compared to after PrEP discontinuation. In contrast, peripheral blood CD4+ and CD8+ T-cells expressing markers of activation and trafficking were increased during PrEP usage. Conclusions: Together, our data are consistent with PrEP altering immunity differentially in the female genital tract compared to circulation in HSV-2+ women. Further study including comparison to HSV-2 negative women is needed to define the overall impact and mechanisms underlying these effects. These results point to the critical need to study the human mucosal compartment to characterize immune responses to mucosal infections
PrEP Discontinuation and Prevention-Effective Adherence: Experiences of PrEP Users in Ugandan HIV Serodiscordant Couples
(Journal of acquired immune deficiency syndromes, 2019) Gilbert, Hannah N.; Wyatt, Monique A.; Pisarski, Emily E.; Muwonge, Timothy R.; Heffron, Renee; Katabira, Elly T.; Celum, Connie L.; Baeten, Jared M.; Haberer, Jessica E.; Ware, Norma C.
Optimal adherence to oral pre-exposure prophylaxis (PrEP) for HIV prevention involves aligning consistent PrEP use with periods of risk to achieve prevention-effective adherence. Prevention-effective adherence is predicated on individuals discontinuing PrEP during periods without expected risk. For stable, serodiscordant couples, ART adherence by the HIV-positive partner markedly decreases HIV transmission risk, potentially obviating the need for continued PrEP use; yet little is known about actual lived experiences of discontinuing PrEP. Methods: In-depth qualitative interviews were carried out with HIV-uninfected PrEP users in serodiscordant couples taking part in the Partners Demonstration Project at IDI-Kasangati, Kampala, Uganda. Open-ended interviews elicited information on the partnered relationship; understandings of PrEP; prevention strategies; and experiences of PrEP discontinuation. An inductive, thematic, content-analytic approach was used to analyze study data. Results: Uninfected partners experienced PrEP as a valued resource for preventing HIV acquisition. Despite ongoing ART use by HIV-positive partners for a period of time consistent with viral suppression, discontinuation of PrEP was experienced as a loss of protection and a corresponding increase in risk of HIV acquisition. Uninfected partners responded with strategies aimed at offsetting this subjective sense of increased risk, specifically: (1) changing sexual practices; (2) prioritizing fidelity in the relationship; (3) increasing reliance on condoms; and (4) seeking evidence of partners’ ART adherence. Conclusions: These experiences highlight the challenges PrEP users in serodiscordant couples face in discontinuing PrEP for prevention-effective adherence. Flexible interventions that support individuals during this transition may increase comfort with discontinuing PrEP when alternative prevention strategies provide protection, such as a partner’s consistent adherence to ART.
PrEP uptake and HIV viral suppression when PrEP is integrated into Ugandan ART clinics for HIV-negative members of HIV-serodifferent couples: A stepped wedge cluster randomized trial
(EClinicalMedicine, 2022) Heffron, Renee; Muwonge, Timothy R.; Thomas, Katherine K.; Nambi, Florence; Nakabugo, Lylianne; Kibuuka, Joseph; Thomas, Dorothy; Feutz, Erika; Meisner, Allison; Ware, Norma C.; Wyatt, Monique A.; Simoni, Jane M.; Katz, Ingrid T.; Kadama, Herbert; Baeten, Jared M.; Mujugira, Andrew
Global scale-up of HIV pre-exposure prophylaxis (PrEP) includes services to HIV-negative people in partnerships with people living with HIV (serodifferent couples). Data are needed on HIV outcomes, including uptake and adherence to PrEP and antiretroviral treatment (ART), to describe the impact of integrating PrEP into an existing HIV program. Methods Using a stepped-wedge cluster randomized trial design, we launched PrEP delivery for HIV-negative members of serodifferent couples in Uganda by integrating PrEP into existing ART programs for people living with HIV. The program provided PrEP training for ART providers, ongoing technical assistance, and a provisional supply chain mechanism for PrEP medication. Primary data on PrEP initiation, PrEP refills, ART initiation, and HIV viremia at 6 months (measured at 42-270 days) were collected through data abstraction of medical records from HIV-serodifferent couples sequentially enrolling at the ART clinics. Modified Poisson regression models, controlling for time and cluster, compared viral suppression (<1000 copies/ml) before and after launch of the PrEP program. This trial was registered at ClinicalTrials.gov, NCT03586128. Findings From June 1, 2018-December 15, 2020, 1,381 HIV-serodifferent couples were enrolled across 12 ART clinics in Kampala and Wakiso, Uganda, including 730 enrolled before and 651 after the launch of PrEP delivery. During the baseline period, 99.4% of partners living with HIV initiated ART and 85.0% were virally suppressed at 6 months. Among HIV-negative partners enrolled after PrEP launched, 81.0% (527/651) initiated PrEP within 90 days of enrolling; among these 527, 11.2% sought a refill 6 months later. In our powered intent-to-treat analysis, 82.1% and 76.7% of partners living with HIV were virally suppressed, respectively, which was not a statistically significant difference (RR=0.94, 95% CI: 0.82-1.07) and was stable across sensitivity analyses. Interpretation Integration of PrEP into ART clinics reached a high proportion of people in HIV-serodifferent relationships and did not improve the already high frequency of HIV viral suppression among partners living with HIV.

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