Tenofovir-Based Preexposure Prophylaxis for HIV Infection Among African Women

Marrazzo, Jeanne M.; Ramjee, Gita; Richardson, Barbra A.; Gomez, Kailazarid; Mgodi, Nyaradzo; Nair, Gonasagrie; Palanee, Thesla; Nakabiito, Clemensia; Straten, Ariane van der; Noguchi, Lisa; Hendrix, Craig W.; Dai, James Y.; Ganesh, Sri; Mkhize, Baningi; Taljaard, Marthinette; Parikh, Urvi M.; Piper, Jeanna; Mâsse, Benoı̂t; Grossman, Cynthia; Rooney, James F.; Schwartz, Jill L.; Watts, Heather; Marzinke, Mark A.; Hillier, Sharon L.; McGowan, Ian; Chirenje, Zvavahera M.

doi:10.1097/01.ogx.0000466878.37011.6f

Cited by 210 publications

(368 citation statements)

References 11 publications

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“…Although the overall protective effect that was observed with the dapivirine vaginal ring was significant, prespecified adherence analyses that were based on a cutoff of 23.5 mg or less in the residual level of dapivirine in used rings and a concentration of 95 pg or more of dapivirine per milliliter of plasma did not show increased protection. Previous trials investigating HIV prevention have shown relationships between adherence to the regimen and HIV-1 protection, [11][12][13] and a similar outcome was anticipated in this trial. However, the prespecified criteria that were based on plasma concentrations and residual levels of dapivirine in the used rings may not be the most appropriate criteria for assessment of adherence.…”

Section: Discussionsupporting

confidence: 79%

“…20 However, in two clinical trials of tenofovir and of tenofovir or tenofovir-emtricitabine oral prophylaxis in participants who are similar to those enrolled in our trial, no protection against HIV-1 infection was observed, because of poor adherence to the daily use of the trial drugs. 11,12 Similarly, in studies that evaluated microbicides, one study of a vaginal gel containing tenofovir showed evidence of protection from HIV-1 infection, 21 but this result was not confirmed in subsequent studies. 12,13 The dapivirine vaginal ring was developed to provide discreet, self-initiated, monthly use with the potential for high adherence.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Similarly, in studies that evaluated microbicides, one study of a vaginal gel containing tenofovir showed evidence of protection from HIV-1 infection, 21 but this result was not confirmed in subsequent studies. 12,13 The dapivirine vaginal ring was developed to provide discreet, self-initiated, monthly use with the potential for high adherence. Most participants were able to use the ring for some time of each month, as shown by the residual levels in the used rings and by the plasma concentrations.…”

Section: Discussionmentioning

confidence: 99%

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Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

et al. 2016

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BACKGROUNDThe incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODSIn this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTSA total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONSAmong women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226.)

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

et al. 2016

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“…This may be important given that detection of study drugs in the samples of completed clinical trials suggests that the majority of participants use PrEP inconsistently. [1,51] The elevated projections associated with the simulation set V4 are results of the rapid emergence of ADR combined with the lowest reversion rates and the worst PrEP protection against resistant HIV assumed (see Fig 2A and 2E). …”

Section: Survey Results: How Virologists Describe Drug-resistance Duementioning

confidence: 99%

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact

DimitrovDobromir

BoilyMarie-Claude

Hallett

2014

AIDS Research and Human Retroviruses

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“…Effective PrEP requires high adherence in MSM [13]. However, PrEP has significantly lower efficacy in women, and requires long-term adherent dosing before any protective efficacy is achieved [14].…”

Section: Introductionmentioning

confidence: 99%

Broad Neutralizing Antibodies to HIV Env and Other Complex Viral Antigens from Vaccinated Cows

Heydarchi¹,

Quiroz²,

Purcell³

2016

J Vaccines Vaccin

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The idea of using antibodies to restrain HIV viral replication has been a growing interest since many years ago. HIV-patient serum with elite virus-neutralizing breadth has led to the preparation of broadly neutralizing antibodies (BrNAbs) with long and highly mutated CDRH3 domains that can neutralize a broad array of viral strains and prevent transmission in animal models. Recent advances have resulted in the discovery of BrNAbs that are more potent and can neutralize many HIV-1 subtypes. However, elicitation of these antibodies in infected individuals usually requires a long time of antigen exposure. Though BrNAbs are shown to be successful either therapeutically or prophylactically against HIV-1, production of these antibodies in bulk, commercial-sized batches are expensive and non-affordable particularly for poor countries. Therefore, more durable preventative or therapeutic strategies are required. Immunization of the cows with HIV Env is shown to be capable of producing 20 kg purified anti-HIV-1 BrNAbs and this amount could be sufficient for 2 million × 10 mg doses for formulation and pre-clinical testing as an HIV microbicide. In addition, bovine immunoglobulins typically have variable third heavy complementarity determining regions (CDRH3) that may potentially facilitate access to antigenic epitopes that are very difficult for other species to engage. Thus, cows could be engaged to elicit anti-HIV antibodies with the features of human BrNAbs and bovine colostrum could be a promising and cheap resource for the development of combination microbicides.

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Tenofovir-Based Preexposure Prophylaxis for HIV Infection Among African Women

Abstract: BACKGROUND-Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

Cited by 210 publications

References 11 publications

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact

Broad Neutralizing Antibodies to HIV Env and Other Complex Viral Antigens from Vaccinated Cows

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