Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

Nel, Annaléne; Bekker, Linda‐Gail; Bukusi, Elizabeth A.; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth T.; Ndaba, Nelisiwe; Straten, Ariane van der; Niekerk, Neliëtte van; Woodsong, Cynthia

doi:10.1371/journal.pone.0147743

Cited by 100 publications

(102 citation statements)

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“…However, the median residual level of dapivirine that was observed in the phase 1-2 trial and in two phase 1 trials 15,16 as well as in the Ring Study was 21 mg and is, therefore, probably a better indicator of sustained adherence to ring use. An exploratory time-varying productadherence analysis in which adherence was defined as a residual level of 21 mg or less of dapivirine in the ring showed a rate of HIV-1 acquisition that was 44% (95% CI, 7 to 67) lower during adherent periods than during nonadherent periods.…”

Section: Discussionmentioning

confidence: 93%

“…The prespecified residual level of more than 23.5 mg of dapivirine in the ring, which was based on data from a phase 1-2 study conducted in sub-Saharan Africa, 15 was used during the trial to identify the proportion of participants in the dapivirine group who were more than 95% likely to be completely nonadherent to the regimen. However, the median residual level of dapivirine that was observed in the phase 1-2 trial and in two phase 1 trials 15,16 as well as in the Ring Study was 21 mg and is, therefore, probably a better indicator of sustained adherence to ring use.…”

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: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Recent trials show the dapivirine vaginal ring to be an effective female controlled method of HIV prevention [1–3]. Their ease of use, potential for longer acting protection, and discreet use independent of coitus have helped rings become a focus for development of HIV prevention intervention delivery [4, 5].…”

Section: Introductionmentioning

confidence: 99%

“…Previous research on contraceptive and HIV prevention rings indicates that only about a quarter of women and their partners felt the ring during sex [3, 6, 26, 27], however, the impact on relationship dynamics and sexual experiences more specifically have not been reported. An understanding of these dynamics and experiences will be critical in encouraging uptake of the ring and regular ring use, now that it has been proven effective [1, 3, 28]. This paper aims to explore the impact of the vaginal ring on women’s sexual experiences, taking into account the gendered relationship context of sexual experiences.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Because of dapivirine's tight binding and lipophilic characteristics, it may be active against both cell-free and cell-associated HIV [122]. Dapivirine is the only microbicide used in human in the form of vaginal rings and believed to be nontoxic [123]. The phase III clinical trials (the ASPIRE study) showed a 27% reduction in HIV-1 acquisition upon using dapivirine vaginal rings [124].…”

Section: Dapivirinementioning

confidence: 99%

Microbicides for the Prevention of HPV, HIV-1, and HSV-2: Sexually Transmitted Viral Infections

Sattar¹,

.²,

Aslam³

et al. 2017

Fundamentals of Sexually Transmitted Infections

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Sexually transmited diseases (STDs) can be transmited through genital-genital, orogenital, or anogenital contacts and remain to be a public health concern worldwide. Approximately one million people around the world are believed to be newly infected with sexually transmited infections (STIs) each day. Numerous causative agents including bacteria, viruses, protozoa, yeast, and fungi are responsible for STIs; however, viruses exhibit more serious risks, probabilities and outcomes of STDs than other organisms. The most lethal viral STIs are human immunodeiciency virus-1 (HIV), herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), and human papillomavirus (HPV), which are responsible for major sexually transmited viral infections including AIDS, herpes simplex, and genital warts, respectively. Despite the fact that several prevention strategies such as vaccination, abstinence from sex, limiting sex partners, the use of condoms and a range of therapeutic drugs have drastically reduced the risk of contracting STIs, these three infections continue to spread at an alarming rate. The high incidence and lack of efective vaccine, instigated scientists to look for alternate, cheap, and eicient strategies for controlling these deadly viruses. Microbicide are relatively new approach that may be helpful in preventing STIs transmission when applied inside the genitals before intercourse. Like other interventions, microbicides are used as prophylactic measures against STIs. Therefore, an excellent safety and eicacy proile analysis is mandatory before their approval for human use. Although no safe and eicacious microbicide is yet available, many candidates including nonoxynol-9, Savvy, cellulose sulfate, Carraguard, VivaGel, tenofovir gel, and PRO 2000 have shown promising in vitro activity and many more are under development. However, very few of them have moved to large-scale phase III trials. This chapter aims to provide a brief overview of various microbicides along with their mechanism of actions and recent updates on safety and efectiveness trials.

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Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

Cited by 100 publications

References 13 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

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

Microbicides for the Prevention of HPV, HIV-1, and HSV-2: Sexually Transmitted Viral Infections

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