Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Wangisi J[original query] |
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Rapid antiretroviral therapy initiation for women in an HIV-1 prevention clinical trial experiencing primary HIV-1 infection during pregnancy or breastfeeding
Morrison S , John-Stewart G , Egessa JJ , Mubezi S , Kusemererwa S , Bii DK , Bulya N , Mugume F , Campbell JD , Wangisi J , Bukusi EA , Celum C , Baeten JM . PLoS One 2015 10 (10) e0140773 During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting. |
Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial
Baeten JM , Donnell D , Mugo NR , Ndase P , Thomas KK , Campbell JD , Wangisi J , Tappero JW , Bukusi EA , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kidoguchi L , Coombs RW , Hendrix C , Marzinke MA , Frenkel L , Haberer JE , Bangsberg D , Celum C . Lancet Infect Dis 2014 14 (11) 1055-1064 BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. METHODS: We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245. FINDINGS: 4410 (99.6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0.71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0.48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0.67, 95% CI 0.39-1.17; p=0.16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0.15, 95% CI 0.06-0.37; p<0.0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0.07, 0.02-0.23; p<0.0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. INTERPRETATION: These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health. |
Successful discontinuation of the placebo arm and provision of an effective HIV prevention product after a positive interim efficacy result: the Partners PrEP Study experience
Ndase P , Celum C , Campbell J , Bukusi E , Kiarie J , Katabira E , Mugo N , Tumwesigye E , Wangisi J , Were E , Brantley J , Donnell D , Baeten JM . J Acquir Immune Defic Syndr 2014 66 (2) 206-12 BACKGROUND: Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations. METHODS: In July 2011, the independent Data and Safety Monitoring Board of the Partners PrEP Study, a randomized, placebo-controlled efficacy trial of daily oral antiretroviral preexposure prophylaxis (PrEP) for HIV prevention among 4747 African heterosexual HIV serodiscordant couples, recommended discontinuation of the trial's placebo arm due to demonstration of PrEP efficacy. We describe dissemination of results, discontinuation of the placebo arm, and provision of active PrEP to participants' formerly assigned placebo. RESULTS: Within 72 hours, of the Data and Safety Monitoring Board meeting the study results were publicly released and disseminated to stakeholders and study participants. Within 3 months, the study protocol was modified to permit participants initially assigned to the study's placebo arm to be offered active PrEP. Of the 1418 participants initially randomized to placebo who were clinically eligible to receive PrEP, 89.1% (1264/1418) consented. CONCLUSIONS: Prompt dissemination of a positive HIV prevention trial result and subsequent provision of effective product to research participants was feasible and efficient for >4700 HIV serodiscordant couples in East Africa. The extent to which study sponsors can assure continued product access to research participants remains a subject of discussion for future HIV prevention clinical trials. |
An intervention to support HIV pre-exposure prophylaxis (PrEP) adherence in HIV serodiscordant couples in Uganda
Psaros C , Haberer JE , Katabira E , Ronald A , Tumwesigye E , Campbell JD , Wangisi J , Mugwanya K , Kintu A , Enyakoit M , Thomas KK , Donnell D , Krows M , Kidoguchi L , Ware N , Baeten JM , Celum C , Bangsberg DR , Safren SA . J Acquir Immune Defic Syndr 2014 66 (5) 522-9 BACKGROUND: Daily pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This manuscript describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence. METHODS: The Partners PrEP Study was a placebo-controlled efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among uninfected members of HIV serodiscordant couples. An ancillary adherence study was conducted at three study sites in Uganda. Participants with <80% adherence as measured by unannounced pill count received an additional adherence counseling intervention based on Lifesteps, an evidence-based HIV treatment adherence intervention, based on principles of cognitive-behavioral theory. FINDINGS: Of the 1,147 HIV seronegative participants were enrolled in the ancillary adherence study, 168 (14.6%) triggered the adherence intervention. Of participants triggering the intervention, 62% were male; median age was 32.5 years. The median number of adherence counseling sessions was 10. Mean adherence during the month before the intervention was 75.7%, and increased significantly to 84.1% in the month after the first intervention session (p<0.001). The most frequently endorsed adherence barriers at session one were travel and forgetting. INTERPRETATION: A PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda and PrEP adherence increased after the intervention. Future research should identify PrEP users with low adherence for enhanced adherence counseling and determine optimal implementation strategies for interventions to maximize PrEP effectiveness. |
Antiretroviral prophylaxis for HIV prevention in heterosexual men and women
Baeten JM , Donnell D , Ndase P , Mugo NR , Campbell JD , Wangisi J , Tappero JW , Bukusi EA , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kakia A , Odoyo J , Mucunguzi A , Nakku-Joloba E , Twesigye R , Ngure K , Apaka C , Tamooh H , Gabona F , Mujugira A , Panteleeff D , Thomas KK , Kidoguchi L , Krows M , Revall J , Morrison S , Haugen H , Emmanuel-Ogier M , Ondrejcek L , Coombs RW , Frenkel L , Hendrix C , Bumpus NN , Bangsberg D , Haberer JE , Stevens WS , Lingappa JR , Celum C . N Engl J Med 2012 367 (5) 399-410 BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.). |
Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention
Mujugira A , Baeten JM , Donnell D , Ndase P , Mugo NR , Barnes L , Campbell JD , Wangisi J , Tappero JW , Bukusi E , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kidoguchi L , Panteleeff D , Krows M , Shah H , Revall J , Morrison S , Ondrejcek L , Ingram C , Coombs RW , Lingappa JR , Celum C . PLoS One 2011 6 (10) e25828 INTRODUCTION: Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort. METHODS: HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months. RESULTS: From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/microL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease. CONCLUSIONS: Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245). |
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