Limited evidence suggests that the non-hormonal contraceptive copper intrauterine device (Cu-IUD) may increase bacterial vaginosis (BV) risk, possibly due to increased volume and duration of menses, ...a common side effect of Cu-IUD use. While increases in bleeding typically resolve within 6-12 months following initiation, evaluations of the association between Cu-IUD and BV have not included more than six months of follow-up.
This secondary analysis of an HIV-1 prevention trial included 2,585 African women ages 18-45 followed for up to 33 months. Women reported contraceptive use each month. BV was evaluated by Nugent score in six-monthly intervals and, if clinically indicated, by Amsel's criteria. Andersen-Gill proportional hazards models were used to (1) evaluate BV risk among Cu-IUD users relative to women using no/another non-hormonal contraceptive and (2) test changes in BV frequency before, while using, and following Cu-IUD discontinuation.
BV frequency was highest among Cu-IUD users at 153.6 episodes per 100 person-years (95% CI: 145.2, 162.4). In adjusted models, Cu-IUD users experienced 1.28-fold (95% CI: 1.12, 1.46) higher BV risk relative to women using no/another non-hormonal contraception. Compared to the six months prior to initiation, BV risk was 1.52-fold (95% CI: 1.16, 2.00) higher in the first six months of Cu-IUD use and remained elevated over eighteen months of use (p<0.05). Among women who discontinued Cu-IUD, BV frequency was similar to pre-initiation rates within one year.
Cu-IUD users experienced elevated BV risk that persisted throughout use. Women and their providers may wish to consider BV risk when discussing contraceptive options.
Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been 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.
BACKGROUND:Long-acting female-initiated methods such as the dapivirine ring may give women greater agency in HIV-1 prevention. However, social harms, defined as nonmedical adverse consequences of ...study participation or dapivirine ring use, may reduce product adherence and consequently HIV-1 protection.
METHODS:We assessed whether experiencing social harms from male partners was associated with lower adherence to the dapivirine ring in the MTN-020/ASPIRE trial. Reports of social harms were solicited quarterly. Low adherence was defined by plasma dapivirine levels ≤95 pg/mL or residual dapivirine levels in returned rings >23.5 mg.
RESULTS:Among 2629 women enrolled in ASPIRE, 85 (3.2%) reported 87 social harms during a median follow-up of 1.6 years. Women were significantly more likely to have low adherence, measured by plasma dapivirine levels, at visits with a social harm in the past month than at visits where no social harm was reported (adjusted risk ratio 2.53, 95% confidence interval1.37 to 4.66, P = 0.003). There was no association for social harms reported ≥1 month prior, suggesting an acute, short-term effect. Women were significantly more likely to not return a ring at visits with a social harm reported (adjusted risk ratio 24.70, 95% confidence interval18.57 to 32.85, P < 0.001). In rings that were returned, social harms were not associated with residual dapivirine levels.
CONCLUSIONS:Although social harms were uncommon (<5% of women with >1 year of use), participants reporting social harms by male partners had lower adherence to the dapivirine ring. Strategies to mitigate nonadherence to product use related to social harms should be evaluated in future studies of female-controlled HIV-1 prevention options.
Purpose of review
Clinical trials have found that the dapivirine vaginal ring (DVR) is safe to use and effective at reducing women’s risk of acquiring HIV infection. As countries prepare for the ...introduction of this novel long-acting, woman-controlled prevention method, an examination of key learnings from oral pre-exposure prophylaxis (PrEP) delivery will help programs leverage successful innovations and approaches to support DVR scale-up and expand the method mix for HIV prevention.
Recent findings
Intensive efforts over the past 5 years have yielded lessons on how to facilitate access to oral PrEP; expand service delivery for PrEP; address the knowledge, attitudes, and skills providers need to support PrEP initiation and effective use; develop messaging that builds community and partner support and combats stigma; and understand the cyclical nature of PrEP use.
Summary
Evidence from oral PrEP introduction and scale-up can help inform and expedite DVR introduction.
Abstract
Background
Confounding introduced by individuals’ sexual risk behavior is potentially a significant source of bias in HIV-1 prevention intervention studies. To more completely account for ...sexual behaviors when assessing the efficacy of the monthly dapivirine ring, a new longer-acting HIV-1 prevention option for women, we estimated per-sex-act risk reduction associated with product use.
Methods
We conducted a secondary analysis of data from MTN-020/ASPIRE, a phase 3, randomized, placebo-controlled efficacy trial of the dapivirine ring that recruited HIV-uninfected, African women aged 18–45 years. With cumulative sex acts as the time scale, we used multivariable Cox regression with inverse probability of censoring weights to estimate HIV-1 risk reduction associated with a rate of dapivirine release indicative of consistent product use.
Results
Women in the dapivirine ring group (n = 1187) had an estimated incidence rate of 2.3 (95% confidence interval CI, 1.8–3.1) HIV-1 acquisition events per 10 000 sex acts versus 3.6 (95% CI, 2.9–4.4) per 10 000 acts in the placebo group (n = 1187). Dapivirine release indicative of consistent ring use was associated with a 63% (95% CI, 33%–80%) per-sex-act HIV-1 risk reduction.
Conclusions
These results support the efficacy of the dapivirine vaginal ring for HIV-1 prevention and help to inform decision-making for women, providers, and policymakers regarding product use.
Clinical Trials Registration
NCT01617096.
Among cisgender African women using the dapivirine vaginal ring for HIV-1 prevention, drug release rates consistent with continuous product use were associated with a 63% (95% CI, 33%–80%) per-sex-act HIV-1 risk reduction, further supporting the product's efficacy.
Abstract
Background
In Kenya, South Africa, and Zimbabwe, oral pre-exposure prophylaxis (PrEP) is recommended for adolescent girls and young women (AGYW) at high risk of HIV. Health providers play a ...critical role in the uptake and effective use of sexual and reproductive health services; however, few published studies have explored providers’ attitudes toward and experiences delivering PrEP to AGYW.
Methods
We conducted a cross-sectional qualitative study, interviewing 113 providers at 36 public, private, and nongovernmental health facilities in Kenya, South Africa, and Zimbabwe that were offering PrEP during the research period or were likely to offer PrEP in the future. Data were coded in NVivo 11, and an applied thematic analysis was conducted.
Results
Most providers preferred that adolescent girls wait until age 18 to have sex but acknowledged that many girls younger than 18 could benefit from oral PrEP. Their primary concern was whether adolescent girls would be able to take PrEP daily, especially if they do not tell their parents or partners they are using it. Providers reported that it was more challenging to deliver PrEP and other HIV services to girls younger than 18. Those with experience providing PrEP pointed to stigma and lack of PrEP awareness in communities as two primary barriers to PrEP uptake and use.
Conclusions
Providers were generally accepting of oral PrEP as an HIV prevention option for AGYW; however, many had negative attitudes about adolescent girls being sexually active and concerns about whether they could take PrEP daily. Results were used to update national PrEP training materials to address negative provider attitudes about PrEP use by AGYW.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women’s risk of sexually acquiring HIV‐1; however, imperfect ring use likely ...diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use.
Methods
We measured the amount of dapivirine in returned rings from a placebo‐controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non‐use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time‐dependent covariate for HIV‐1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV‐1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence.
Results
Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV‐1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV‐1 acquisition estimated 75% to 91% HIV‐1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall.
Conclusions
Residual dapivirine levels, an objective measure of adherence, were correlated with HIV‐1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long‐acting, woman‐initiated approach for discreet HIV‐1 prevention.
BACKGROUND:Monthly use of the dapivirine vaginal ring has been shown to be safe and effective for HIV-1 prevention in nonpregnant reproductive-aged women. The impact of dapivirine on pregnancy ...outcomes and infant is not known. We compared pregnancy incidence and outcomes by study arm among HIV-1–uninfected women who became pregnant while participating in MTN-020/ASPIRE.
METHODS:ASPIRE was a randomized, double-blind, placebo-controlled phase III safety and effectiveness study of the dapivirine ring for HIV-1 prevention. Sexually active women aged 18–45 years from Malawi, South Africa, Uganda, and Zimbabwe were enrolled. Urine pregnancy tests were performed monthly, and, if positive, study product was withheld during pregnancy and breastfeeding. Pregnancy-related outcomes included the followingpregnancy incidence, pregnancy outcomes (live birth, preterm birth, pregnancy loss, and congenital anomalies), and infant growth.
RESULTS:Of 2629 women enrolled in ASPIRE, 169 became pregnant during follow-up, resulting in 179 incident pregnancies and 181 pregnancy outcomes. No difference in pregnancy incidence by study arm was observed (hazard ratio = 0.93; 95% confidence interval0.68 to 1.26). The distribution of pregnancy outcomes was similar by study arm, and no difference was noted in the frequency or pattern of congenital anomalies or infant growth parameters by study arm.
CONCLUSIONS:Dapivirine use in the periconception period does not seem to be associated with adverse effects on pregnancy or infant outcomes. Our findings provide support for additional safety studies of the dapivirine ring throughout pregnancy.
The dapivirine vaginal ring reduces the risk of HIV-1 acquisition in acts of vaginal intercourse (VI), and although it does not offer HIV-1 protection in acts of anal intercourse (AI), it may provide ...some overall risk reduction for women for whom most sex acts are vaginal. We estimated the protective effect of the ring among women with high ring adherence engaged in both VI and AI.
We developed a microsimulation model using data from the MTN-020/ASPIRE trial. Among women who reported any AI, we estimated the proportion of all sex acts that were AI. Model scenarios varied this proportion among women engaged in both VI and AI from 5% to 30%, including the trial-observed median proportion of 6.3% of all acts being AI. In primary analyses, dapivirine ring efficacy was model-calibrated at 70% for vaginal exposures and assumed to be 0% for anal exposures.
Among highly adherent women for whom 6.3% of sex acts were AI, the ring reduced HIV-1 risk by 53% (interquartile range: 44, 60), with a decline to 26% (interquartile range: 16, 36) among women for whom 30% of acts were AI. Ring effectiveness was less than 40% among women for whom AI accounted for greater than 16% of all sex acts, although this represented less than 5% of all women in the ASPIRE trial.
For most women, including those who engage in AI, because most HIV-1 risk occurs in acts of vaginal sex, the dapivirine vaginal ring can provide important HIV-1 protection.
BACKGROUND:In MTN-020/ASPIRE, a dapivirine vaginal ring effectiveness trial in sub-Saharan Africa, we assessed whether worries about ring use changed over time and were associated with adherence.
...METHODS:Participants (N = 2585) were surveyed at baseline and follow-up about worries regarding daily ring use. First, they answered a question about general worries and then responded to 15 items covering specific worries. From a nested qualitative component (N = 214), we extracted themes related to ring worries and adherence. Seven months into the trial, aggregate adherence data were shared with study sites as part of an intervention that included counseling and social support. Nonadherence was defined as dapivirine plasma levels of ≤95 pg/mL. Mixed-effect logistic regression models were used to assess changes in ring worries and nonadherence from baseline to month 3 and later.
RESULTS:Worry about wearing the ring decreased from 29% at baseline to 4% at month 3 (P < 0.001), while having a specific worry decreased from 47% to 16% (P < 0.001). Among those enrolled before intervention, 29% with baseline worries were nonadherent at month 3 (95% confidence interval19% to 39%) compared to 14% without worries (95% confidence interval9% to 19%; P = 0.005); the difference persisted through month 6. There was no difference in nonadherence by baseline worry for those enrolled after intervention (P = 0.40). In the qualitative subset, initial ring anxieties reportedly subsided with self-experimentation and practice and the beneficial influence of the intervention.
CONCLUSIONS:Although worries may be an initial deterrent to correct ring use, intervening early by leveraging social influences from peers and clinicians should facilitate successful adoption and correct ring use.
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