Background: Pregnancy represents a period of high HIV acquisition risk. Safety data for the monthly dapivirine vaginal ring (DVR) during pregnancy are limited. Here, we report data from the first 2 cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC).
View Article and Find Full Text PDFJ Int AIDS Soc
November 2023
Introduction: Effective use of pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in sub-Saharan Africa. The MTN-034/REACH trial offered AGYW a menu of adherence support strategies and achieved high adherence to both daily oral PrEP and the monthly dapivirine vaginal ring. Understanding how these strategies promoted product use could inform the design of adherence support systems in programmatic settings.
View Article and Find Full Text PDFBackground: Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women.
View Article and Find Full Text PDFBackground: Clinical trials of dapivirine (DPV) vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for DPV ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network-025/HIV Open-label Prevention Extension (HOPE) study of DPV ring.
View Article and Find Full Text PDFAs part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines.
View Article and Find Full Text PDFIntroduction: Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation.
Methods: AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months.
Antimicrob Agents Chemother
November 2022
Data to inform behaviorally congruent delivery of rectal microbicides as lubricants are scant. Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor which has been demonstrated to be well-tolerated and efficacious in multiple clinical trials when used in a vaginal ring formulation. DPV gel administered rectally with an applicator was found to be well-tolerated in a phase 1 clinical trial.
View Article and Find Full Text PDFThe Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.
View Article and Find Full Text PDFBackground: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.
Methods: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.
Introduction: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV.
Methods: MTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015.
Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen.
View Article and Find Full Text PDFWe triangulated quantitative and qualitative assessments to evaluate participants' acceptability of 0.05% dapivirine rectal microbicide (RM) gel administered via two separate modalities (a rectal applicator and an artificial phallus for use as a coital simulation device) as part of a Phase I trial (N = 14) among men who have sex with men (MSM) randomized using a 1:1 ratio. Overall, participants reported favorable acceptability of the gel (n = 11; 78.
View Article and Find Full Text PDFBackground: Two 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.
Methods: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]).
J Acquir Immune Defic Syndr
February 2020
Background: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence.
View Article and Find Full Text PDFInt Perspect Sex Reprod Health
December 2019
Context: The copper IUD is safe and effective, but underutilized in Sub-Saharan Africa, in part because of a lack of trained providers. The World Health Organization recommends training mid-level providers-including nurses and midwives-to insert IUDs; however, the safety of such task shifting has not been evaluated in Sub-Saharan Africa.
Methods: Data were drawn from baseline surveys and study charts of 535 sexually active women aged 18-45 who used a copper IUD while participating in an HIV-prevention clinical trial conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda and Zimbabwe.
Objective: Observational studies have associated use of intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM) with increased risk of HIV-1 acquisition, but limited data are available to assess HIV-1 risk for alternate contraceptive methods.
Methods: Within a randomized trial of the dapivirine vaginal ring for HIV-1 prevention, we assessed HIV-1 incidence by contraceptive method. We limited analyses to participants from South African sites and to women who used DMPA-IM, the alternative injectable norethisterone enanthate, implants, or copper intrauterine devices (IUDs).
Objective: Long-acting reversible contraceptive (LARC) method uptake has been low within the context of HIV prevention trials. Within a multinational study (MTN-020/ASPIRE), the Contraceptive Action Team improved LARC accessibility and uptake. In this secondary analysis, we determined the rate of contraceptive method continuation among the women enrolled.
View Article and Find Full Text PDFBackground: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.
View Article and Find Full Text PDFObjective: To simplify airway management and minimize cardiopulmonary resuscitation (CPR) chest compression interruptions, some emergency medical services (EMS) practitioners utilize supraglottic airway (SGA) devices instead of endotracheal intubation (ETI) as the primary airway adjunct in out-of-hospital cardiac arrest (OHCA). We compared the outcomes of patients receiving ETI with those receiving SGA following OHCA.
Methods: We performed a secondary analysis of data from the multicenter Resuscitation Outcomes Consortium (ROC) PRIMED trial.
Purpose: To determine whether the Medical Student Well-Being Index (MSWBI) can serve as a brief assessment tool to identify medical students in severe psychological distress.
Method: The authors used data from 2,248 medical students at seven U.S.
Background And Rationale: Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients.
Methods: The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity.
Hot flashes are a complication of androgen deprivation therapy for prostate cancer. A phase III study showed that use of low-dose gabapentin was well tolerated and moderately decreased the frequency of hot flashes due to androgen deprivation therapy when taken for 4 weeks. The current study, an open-label continuation of the randomized study, examined the efficacy and toxicity of gabapentin when taken for (an additional) 8 weeks.
View Article and Find Full Text PDFBackground: Several studies have demonstrated the importance of personality constructs on health behaviors and health status. Having a pessimistic outlook has been related to negative health behaviors and higher mortality. However, the construct has not been well explored in cancer populations.
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