Abstract
MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, − 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up. A total of 1456 women (median age 31 years) enrolled, 1342 (92.2%) accepted the ring at baseline and 1163 (79.9%) accepted the ring(s) at all visits. Changing ring dispensation from a monthly to a quarterly schedule had no negative effect on acceptance. Having a primary partner and him knowing about the ring being offered in HOPE, use of long-acting contraception (implants, injections, IUDs) or sterilization were associated with ring acceptance, along with prior strong intention to use the ring in the future. Efforts should consider these factors when rolling out the ring for HIV prevention.
Keywords: dapivirine vaginal ring, HIV Pre-Exposure Prophylaxis, microbicide, acceptance, African women, choice
Introduction
Globally, women continue to be disproportionately affected by HIV due to biological, social, cultural and economic factors [1]. Available HIV prevention products such as internal and external condoms and daily oral pre-exposure prophylaxis (PrEP) may not suit all women [2]. Condom use requires negotiation and/or male action [3] and daily oral PrEP can be burdensome, easy to forget, and stigmatizing [4, 5]. Thus, more HIV prevention options that are discreet, controlled by women and user-friendly are still needed [6], and the dapivirine vaginal ring may address some of these needs.
Results from two phase III placebo-controlled clinical trials (the IPM 027/The Ring Study (N = 1959) and MTN-020/ASPIRE (N = 2629)) assessed the safety and effectiveness of the ring among a total of 4,588 African women aged 18–45 years and found it well-tolerated, effective and acceptable, with HIV risk reduced by about 30% overall [7–10]. A post-hoc analysis of ASPIRE data found that consistent use was associated with a risk reduction of over 50% [11]. Two phase IIIb open label studies (IPM 032/DREAM and MTN-025/HOPE) provided former participants from the ASPIRE and Ring Study trials with access to the ring, along with assessing additional safety data, uptake and adherence to the ring in the context of known efficacy [12, 13].
The European Medicines Agency gave a positive opinion on the ring’s use, along with safer sex practices for women who cannot or are unable to use daily oral PrEP in July 2020 and in January 2021, the ring received World Health Organization [WHO] recommendation as an additional HIV prevention choice for women at substantial risk for HIV acquisition[14, 15]. Zimbabwe and South Africa have approved the ring for use, with regulatory reviews pending in additional African countries [16, 17].
As a new PrEP approach, the rollout of the ring will require further insight on the acceptance (or uptake), adherence, along with appropriateness [18], and acceptability [19, 20] of the ring outside of randomized clinical trials, as highlighted by the PrEP end-user journey [21]. In the HOPE open label extension trial, women who previously participated in ASPIRE were offered access to the ring for a year. One secondary objective in HOPE was to better understand initial and continued acceptance of the ring – defined here as a woman’s consent to receive the ring when offered, in a context of choice and demonstrated efficacy [22–24]. We therefore sought to assess trend in ring acceptance and to explore baseline factors associated with uptake of the ring initially as well as continued acceptance in MTN-025/HOPE, an important consideration for future rollout of the ring in African countries.
Methods
Study design and participants
MTN025/HOPE was conducted at 14 sites in Malawi, South Africa, Uganda and Zimbabwe between July 2016 to October 2018 [12]. HOPE was designed to offer access to the ring for 12 months followed by 1 month without product for a total of 13 months. However, participants could be enrolled for a shorter duration, with as little as 3 months of ring use possible (i.e. baseline, month-1 and month-2 follow up visits).
Women had to be former ASPIRE participants, HIV seronegative, not pregnant, not breastfeeding, willing to provide informed consent, willing to use contraceptive methods and generally in good health to be eligible for the HOPE study.
Procedures
Enrollment visit was conducted within 56 days of the screening visit followed by monthly visits for the first 3 months, and thereafter quarterly visits at months 3, 6, 9. The product use end visit (PUEV) was conducted at month-12 and a termination visit was conducted 4 weeks after PUEV. HIV prevention Options Counselling was provided at the HOPE enrollment visit and thereafter at all scheduled follow-up visits (months 1, 2, 3, 6, and 9). This counselling was offered in a standardized manner and supervised across all HOPE sites ensuring that all participants received all information required to make an informed choice on the HIV prevention method to use with minimal bias. Women were offered the ring at every scheduled visit (if there was not a concern warranting the ring being held) and could choose to accept it or not. Unscheduled visits could happen to address different concerns or to continue with procedures that could not take place in a previous scheduled visit, including the resumption of study product if previously held. Women who accepted the ring(s) during a visit were classified as acceptors for the corresponding month (or quarter), while women who declined the ring(s) were classified as non-acceptors. Visits after censoring events (i.e., pregnancy, confirmed HIV seroconversion, relocation/lost to follow-up, or death) were treated as missing values. Conversely, a participant who decided to exit the study early was classified as a non-acceptor, as we considered the participant as no longer interested in using the ring. When a visit was missed for reasons other than the participant’s decision, and there was a ring decision in a subsequent interim visit, this decision was classified as that of the missed visit; if there was no decision at a subsequent interim visit (or no interim visit), then the ring decision was classified as a missing value. When the visit was missed due to the participant refusing to attend the clinic, this was classified as non-acceptance. All participants were educated about the ASPIRE results prior to making a decision to join the HOPE study. We used several resources to educate women about the efficacy such as fact sheets and information in the consent forms. Understanding the ASPIRE efficacy results was also a required point of comprehension prior to consenting to participate in the HOPE study.
Statistical analyses
We assessed three binary outcomes related to ring acceptance: a participant could accept the ring at the enrollment visit, a participant could accept the ring at every visit, and a participant could accept the ring at enrollment but decline the ring in the last scheduled visit. The analyses performed for each of these three binary outcomes are detailed in this section.
First, we explored the association between acceptance of the ring at the enrollment visit (initial acceptance) and participants’ baseline characteristics (i.e. demographics, sexual behavior, HIV risk perception, contraceptive method). A univariate logistic regression and a likelihood ratio test was performed for each covariate to assess potential association with acceptance of the ring. Covariates that were statistically significant (p-value < 0.10) were included in a multivariate logistic regression. Every logistic regression was adjusted by geographical region of the study site: Durban, South Africa; South Africa outside of Durban; and Eastern/Southern Africa (Malawi, Uganda, Zimbabwe). We used robust standard errors for the construction of 95% confidence intervals for the odds ratios estimates.
Next, we defined a consistent acceptor as a participant that accepted the ring at all visits when the choice was available to them. We explored the association between being a consistent acceptor and baseline covariates by comparing the percentages of consistent ring acceptors and non-acceptors in the different categories of each covariate. We also fitted an univariable logistic regression adjusted by region and number of visits per participant, which were treated as potential confounders. Likelihood ratio tests were performed reporting odds ratios estimates with robust 95% confidence intervals and p-values from them. Statistically significant covariates (p-value < 0.10) were included in a multivariable logistic regression adjusted by region and number of visits.
Lastly, we further explored change in ring acceptance between enrollment and month 9, the last visit where a ring choice could be made, and whether these changes (from accepting to not-accepting) were related to a change in relationship status (i.e. from having a primary partner to no primary partner) or a change in the type of contraceptive method (i.e. from using a long-acting method to using none or a short-acting method), since these two covariates were associated with ring acceptance at baseline. This sub-analysis was restricted to participants that accepted the ring at enrollment and completed a month 9 visit. We compared the percentage of participants that changed their decision and declined the ring at month 9 (regardless of their ring choice at earlier follow up visits), versus the percentage that accepted the ring at month 9. Using the chi-squared test and a significance level of p-value < 0.10, we assessed if the change in ring choice could be explained by change in either of the two covariates of interest.
Study oversight
The study was funded by the U.S. National Institutes of Health (ClinicalTrials.gov NCT02858037). Written informed consent was obtained from each study participant. Study conduct adhered to international guidelines, and the study was approved initially and annually by an institutional review board or ethics committee at each site and corresponding collaborating institutions in the United States.
Results
Study population and visits
A total of 1456 participants (median age 31 years) enrolled in the HOPE study (Table I). There were 529 (36.3%) participants from Durban, 176 (12.1%) participants from South Africa outside of Durban, and 751 (51.6%) participants from Eastern/Southern Africa (Malawi, Uganda, Zimbabwe). Participants from different regions differed in most of the baseline characteristics considered in this study.
Table I.
HOPE cohort participant’s baseline characteristics overall and by region
| Baseline characteristic | Overall | Durban, SA | Outside Durban, SA | Eastern or Southern Africa | ||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| N | (%) | N | (%) | N | (%) | N | (%) | |
| Total | 1456 | (100) | 529 | (100) | 176 | (100) | 751 | (100) |
| Age < 25 years old | 181 | (12.4) | 117 | (22.1) | 27 | (15.3) | 37 | (4.9) |
| Currently married | 686 | (47.1) | 54 | (10.2) | 34 | (19.3) | 598 | (79.6) |
| Completed secondary school or higher | 1196 | (82.1) | 503 | (95.1) | 171 | (97.2) | 522 | (69.5) |
| ≥ 1 alcoholic drink/week | 278 | (19.1) | 92 | (17.4) | 68 | (38.6) | 118 | (15.7) |
| Smokes ≥ 1 cigarette/day | 68 | (4.7) | 32 | (6.0) | 24 | (13.6) | 12 | (16) |
| Any vaginal sex in last 7 days | 1022 | (70.2) | 319 | (60.3) | 120 | (68.2) | 583 | (77.6) |
| Any unprotected vaginal sex in last 7 days | 676 | (46.4) | 156 | (29.5) | 58 | (33.0) | 462 | (61.5) |
| Has a primary partner | 1399 | (96.1) | 504 | (95.3) | 173 | (98.3) | 722 | (96.1) |
| Primary partner has positive or unknown status | 576 | (39.6) | 165 | (31.2) | 63 | (35.8) | 348 | (46.3) |
| With primary partner who knows participant is taking part in the study | ||||||||
| Yes | 1080 | (74.2) | 389 | (73.5) | 131 | (74.4) | 560 | (74.6) |
| No/not sure | 319 | (21.9) | 115 | (21.7) | 42 | (23.9) | 162 | (21.6) |
| No primary partner | 57 | (3.9) | 25 | (4.7) | 3 | (1.7) | 29 | (3.9) |
| With primary partner who knows participant was offered to use the ring | ||||||||
| Yes | 952 | (65.4) | 342 | (64.7) | 119 | (67.6) | 491 | (65.4) |
| No/not sure | 447 | (30.7) | 162 | (30.6) | 54 | (30.7) | 231 | (30.8) |
| No primary partner | 57 | (3.9) | 25 | (4.7) | 3 | (1.7) | 29 | (3.9) |
| ≥ 1 sexual partner | 272 | (18.7) | 78 | (14.7) | 63 | (35.8) | 131 | (17.4) |
| Anal sex in past 3 months (∞) | ||||||||
| Yes | 99 | (6.8) | 55 | (10.4) | 19 | (10.8) | 25 | (3.3) |
| No | 1348 | (92.6) | 473 | (89.4) | 151 | (85.8) | 724 | (96.4) |
| Current HIV risk perception (∞) | ||||||||
| Not worried | 579 | (39.8) | 217 | (41.0) | 88 | (50.0) | 274 | (36.5) |
| Somewhat worried | 534 | (36.7) | 168 | (31.8) | 55 | (31.2) | 311 | (41.4) |
| Very worried | 342 | (23.5) | 144 | (27.2) | 32 | (18.2) | 166 | (22.1) |
| Contraceptive Method | ||||||||
| Implant | 345 | (23.7) | 94 | (17.8) | 32 | (18.2) | 219 | (29.2) |
| Injectable | 569 | (39.1) | 257 | (48.6) | 85 | (48.3) | 227 | (30.2) |
| Intrauterine device (IUD) | 265 | (18.2) | 59 | (11.2) | 32 | (18.2) | 174 | (23.2) |
| Combined Oral Contraceptive (COC) | 205 | (14.1) | 87 | (16.4) | 21 | (119) | 97 | (12.9) |
| Sterilization | 72 | (4.9) | 32 | (6.0) | 6 | (3.4) | 34 | (4.5) |
| Uses a long-acting contraceptive method or sterilization | 1251 | (85.9) | 442 | (83.6) | 155 | (88.1) | 654 | (87.1) |
| Perceives the ring offers a lot of protection (∞) | ||||||||
| No | 343 | (23.6) | 103 | (19.5) | 39 | (22.2) | 201 | (26.8) |
| Yes | 1110 | (76.2) | 423 | (80.0) | 137 | (77.8) | 550 | (73.2) |
| Very likely to use the ring if it becomes available (*) (∞) (†) | ||||||||
| No | 378 | (26.0) | 153 | (28.9) | 46 | (26.1) | 179 | (23.8) |
| Yes | 931 | (63.9) | 252 | (47.6) | 125 | (71.0) | 554 | (73.8) |
| Willing to participate in a future ring study (*) (∞) | ||||||||
| No | 38 | (2.6) | 6 | (1.1) | 14 | (8.0) | 18 | (2.4) |
| Yes | 1352 | (92.9) | 506 | (95.7) | 157 | (89.2) | 689 | (91.7) |
Question asked at the exit visit from the ASPIRE trial.
The total counts do not add to 100% due to missing values
Missing data largely attributable to transmission errors in ACASI data that occurred at two sites in the Durban area (9)
Due to women enrolling at different calendar times during HOPE, not all of them were followed for all six visits with ring access (enrollment through Month-9 visit): 1419 (97.5%) were expected to complete all six visits, 13 (0.9%) were expected to complete five visits, 9 (0.6%) were expected to complete four, and 15 (1.0%) were expected to complete three visits. Figure 1 shows the flow of the participants through this study, describing at each visit: the number of participants remaining in the study and the number of visits included in the analysis. Overall, a total of 40 participants (2.7%) were eventually excluded from analysis due to pregnancy and 25 (1.7%) HIV seroconverted.
Fig. 1.
Consort diagram detailing the ring decisions of enrolled participants recorded throughout the study. Each month at the beginning of the study and each quarter after the fourth visit (Month-3 visit) participants successfully completed a visit where a ring decision was made, completed an interim visit or declined to do the visit (considered non-acceptors) [middle boxes], whereas some participants either missed the visit or were in clinical hold [right boxes]. The number of participants that were censored from our analysis in between visits are detailed in the hexagons [left of figure]. (*) women enrolled late in HOPE were not expected to complete all follow-up visits, and were offered a tailored schedule with PUEV occurring at a visit earlier than the month-12 visit
Of the total 8660 ring access visits expected, 8364 (96.6%) visits could be classified with a ring acceptance decision. The remaining 296 visits (3.4%) were excluded from analysis because the primary outcome (ring acceptance) could not be assessed due to a missed visit, a product hold while the study team investigated possible pregnancy, incident HIV or adverse events, or early termination from the study. Of the 8364 visits, 7397 (88.4%) were coded as ring acceptance visits and 967 (11.6%) were coded as ring non-acceptance visits.
Ring acceptance
At enrollment, 1342 (92.2%) women accepted the ring as part of their HIV prevention options while 114 (7.8%) declined the ring. Table II shows the association of baseline covariates and participants’ decisions to accept the ring or not at enrollment.
Table II.
Baseline correlates of initial acceptance of the ring in HOPE
| Univariable logistic regressions | Multivariable logistic regression | |||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Ring initial acceptance | Non-acceptors | Acceptors | Odds ratio | p-value | Odds ratio | p-value | ||
| N | (%) | N | (%) | OR (95% CI) | OR (95% CI) | |||
| Total | 114 | (7.8%) | 1342 | (92.2) | ||||
| Baseline Covariates | ||||||||
| Age | 0.403 | |||||||
| < 25 | 23 | (20.2) | 158 | (11.8) | Ref | |||
| ≥ 25 | 91 | (79.8) | 1184 | (88.2) | 1.24 (0.75, 2.06) | |||
| Marital status | 0.674 | |||||||
| Single | 85 | (74.6) | 685 | (51.0) | Ref | |||
| Married | 29 | (25.4) | 657 | (49.0) | 1.13 (0.63, 2.03) | |||
| Education level | 0.265 | |||||||
| < Secondary level | 15 | (13.2) | 245 | (18.3) | Ref | |||
| ≥ Secondary level | 99 | (86.8) | 1097 | (81.7) | 1.44 (0.78, 2.66) | |||
| Alcoholic drinks per week 0 | 91 | (79.8) | 1087 | (81.0) | Ref | 0.961 | ||
| ≥ 1 | 23 | (20.2) | 255 | (19.0) | 0.99 (0.61, 1.61) | |||
| Cigarettes per day | ||||||||
| 0 | 111 | (97.4) | 1277 | (95.2) | Ref | 0.064 | Ref | 0.387 |
| ≥ 1 | 3 | (2.6) | 65 | (4.8) | 2.66 (0.82, 8.64) | 1.64 (0.50, 5.44) | ||
| Vaginal sex acts in the last 7 days | ||||||||
| No | 49 | (43.0) | 385 | (28.7) | Ref | 0.052 | Ref | 0.903 |
| Yes | 65 | (57.0) | 957 | (71.3) | 1.49 (0.996, 2.24) | 1.03 (0.62, 1.70) | ||
| Has a primary partner | ||||||||
| No | 15 | (13.2) | 42 | (3.1) | Ref | < 0.001 | ||
| Yes | 99 | (86.8) | 1300 | (96.9) | 4.92 (2.50, 9.66) | |||
| Primary partner knows participant is taking part in the study | < 0.001 | |||||||
| No/Unsure | 30 | (26.3) | 289 | (21.5) | Ref | |||
| Yes | 69 | (60.5) | 1011 | (75.3) | 1.53 (0.97, 2.41) | |||
| No primary partner | 15 | (13.2) | 42 | (3.1) | 0.28 (0.13, 0.59) | |||
| Primary partner knows participant was offered the ring (*) | < 0.001 | 0.001 | ||||||
| No/Unsure | 48 | (42.1) | 399 | (29.7) | Ref | 2.52 (0.97, 6.53) | ||
| Yes | 51 | (44.7) | 901 | (67.1) | 2.18 (1.43, 3.31) | 4.62 (1.82, 11.77) | ||
| No primary partner | 15 | (13.2) | 42 | ((3.1) | 0.32 (0.16, 0.67) | Ref | ||
| Number of sexual partners other than primary | ||||||||
| 0 | 96 | (84.2) | 1088 | (81.1) | Ref | 0.450 | ||
| ≥ 1 | 18 | (15.8) | 254 | (18.9) | 1.23 (0.71, 2.12) | |||
| Anal sex in past 3 months | 0.788 | |||||||
| No | 103 | (90.4) | 1245 (93.4) | Ref | ||||
| Yes | 11 | (9.6) | 88 (6.6) | 0.91 (0.46, 1.80) | ||||
| HIV risk perception | 0.311 | |||||||
| Not/somewhat worried | 90 (78.9) | 1023 (76.3) | Ref | |||||
| Very worried | 24 (21.1) | 318 (23.7) | 1.27 (0.79, 2.04) | |||||
| Contraceptive method | ||||||||
| Condoms/Combined Oral Contraceptives (COC) | 31 (27.2) | 174 (13.0) | Ref | 0.009 | ||||
| Injectable | 44 (38.6) | 525 (39.1) | 2.36 (1.43, 3.90) | |||||
| Implant | 22 (19.3) | 323 (24.1) | 2.14 (1.18, 3.88) | |||||
| IUD | 13 (11.4) | 252 (18.8) | 2.68 (1.33, 5.41) | |||||
| Sterilization | 4 (3.5) | 68 (5.1) | 3.20 (1.09, 9.36) | |||||
| Type of contraceptive method | ||||||||
| Short-acting (condoms, COC) | 31 (27.2) | 174 (13.0) | Ref | < 0.001 | Ref | 0.01 | ||
| Long-acting + Sterilization | 83 (72.8) | 1168 (87.0) | 2.39(1.51, 3.79) | 2.10 (1.21, 3.63) | ||||
| Perceives the ring offers high protection | ||||||||
| No | 37 (33.3) | 306 (22.8) | Ref | 0.002 | Ref | 0.065 | ||
| Yes | 74 (66.7) | 1036 (77.2) | 1.98 (1.29, 3.05) | 1.62 (0.97, 2.69) | ||||
| Covariates reported at the end of ASPIRE follow-up | ||||||||
| Very likely to use the ring if it becomes available | ||||||||
| No | 39 (44.3) | 339 (27.8) | Ref | 0.011 | Ref | 0.018 | ||
| Yes | 49 (55.7) | 882 (72.2) | 1.8 (1.15, 2.8) | 1.77 (1.11, 2.83) | ||||
| Willing to participate in a future ring study | ||||||||
| No | 3 (2.9) | 35 (2.7) | Ref | 0.749 | ||||
| Yes | 102 (97.1) | 1250 (97.3) | 1.23 (0.37 4.05) | |||||
Comparison of covariates between initial ring acceptors and non-acceptors at baseline; odds ratios estimates and robust 95% confidence intervals from univariate logistic regressions adjusted by region; p-values obtained from likelihood ratio tests; odds ratios estimates and robust 95% confidence intervals from a multivariable logistic regression adjusted by region.
reference group was changed for multivariable analysis to better illustrate the positive association with both having a primary partner at enrollment, and him knowing about the ring
Significant covariates (p-value < 0.10) in univariable analyses included: being a smoker, engaging in any vaginal sexual act (either unprotected or protected by condom) in the previous 7 days, having a primary partner, using a long-acting contraceptive method (implant, injectable, IUD) or sterilization, perceiving the ring provides a high level of protection and reporting at the end of ASPIRE a strong intention to use the ring if it becomes available in the future.
Having a primary partner had the strongest positive association with initially accepting the ring, adjusting for region [OR: 4.92, 95% CI: 2.50–9.66]. Furthermore, having a primary partner with knowledge of the ring being offered in HOPE increased the odds of initially accepting the ring [OR: 2.18, 95% CI: 1.43–3.31]. Importantly, the association was specifically with the partner’s knowledge of the ring and not with the partner’s knowledge about the participant’s involvement in the HOPE trial.
The type of contraceptive method a woman used was also associated with initially accepting the ring (p-value < 0.10). Compared to using a short-acting contraceptive method (such as condoms or oral pills), each long-acting contraceptive method had a positive association to accepting the ring at baseline. The odds of ring acceptance among women in the same region more than doubled when they used a long-acting contraceptive method or sterilization, rather than a short-acting one (OR: 2.24; 95% CI: 1.41–3.55). Perceiving the ring offered a high level of protection was associated with initial ring acceptance [OR: 1.98, 95% CI: 1.29–3.05), as was reporting to be very likely to use the ring if it ever becomes available [OR:1.80, 95% CI: 1.15–2.80).
Although the odds ratio for smokers was positively associated with initial acceptance of the ring (OR; 2.66, 95% CI: 0.82–8.64), it was not statistically significant (p-value≥ 0.10).
We constructed a multivariable logistic model with all the significant covariates (at p-value < 0.10; see Table II). To avoid collinearities between variables in the model, only one composite variable of primary partner status was included: the primary partner’s knowledge of the participant being offered the ring. Similarly, we dichotomized contraceptive use as either short-acting or long-acting plus sterilization.
In the multivariable logistic model, most variables remained statistically significant (p-value < 0.10), except for being a smoker and having any vaginal sex 7 days prior to the enrollment visit. Under this multivariable model, we found that having a primary partner, this primary partner knowing the ring was offered, using a long-acting contraceptive method or sterilization, perception that the ring offered a high level of protection and being very likely to use the ring if it becomes available were all positively associated with ring initial acceptance. Having a primary partner with knowledge of a participant’s option to use the ring displayed the strongest association: the odds of accepting the ring for women with a primary partner who knew about the ring was 4.62 (95% CI: 1.82–11.77) times the odds for women from the same region without a primary partner, when all other covariates remained the same. The odds ratio for women with a primary partner without knowledge about the ring was also elevated but was not statistically significant [OR: 2.52, 95%CI: 0.97–6.53].
The odds ratio for participants using sterilization or long-acting contraceptive methods was positively associated with ring acceptance compared to women on short-acting contraceptive method, adjusting by region and by other significant covariates. [OR: 2.10, 95%CI: 1.21–3.63].
Overall, 1163 (79.9%) participants were consistent acceptors, meaning they accepted the ring at every ring access visit. Among the 293 (20.1%) non-consistent acceptors, 89 (6.1%) never accepted the ring and 204 (14.0%) had intermittent patterns of ring acceptance.
Table III shows the association of baseline covariates and participants’ consistent ring acceptor status throughout HOPE follow-up.
Table III.
Baseline correlates of consistent acceptance of the ring in HOPE
| Univariable logistic regressions | Multivariable logistic regression | |||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Ring acceptance | Non-consistent acceptors | Consistent acceptors | Odds ratio | p-value | Odds ratio | p-value | ||
| N | (%) | N | (%) | OR (95% CI) | (95% CI) | |||
| Total | 293 | (20.1) | 1163 | (79.9%) | ||||
| Covariates reported at enrollment in HOPE | ||||||||
| Age (years) | 0.982 | |||||||
| < 25 | 49 | (16.7) | 132 | (11.3) | Ref | |||
| ≥ 25 | 0.817 | |||||||
| Marital status | 24 | (83.3) | 1031 | (88.7) | 1.0 (0.69, 1.46) | |||
| Single | 209 | (71.3) | 561 | (48.2) | Ref | |||
| Married | 84 | (28.7) | 602 | (51.8) | 1.05 (0.71, 1.55) | |||
| Education level | 0.027 | 0.058 | ||||||
| < Secondary level | 42 | (14.3) | 218 | (18.7) | Ref | Ref | ||
| ≥ Secondary level | 251 | (85.7) | 945 | (81.3) | 1.60 (1.06, 2.42) | 1.56 (0.99, 2.45) | ||
| Alcoholic drinks per week | 0.318 | |||||||
| 0 | 227 | (77.5) | 951 | (81.8) | Ref | |||
| ≥ 1 | 66 | (22.5) | 212 | (18.2) | 0.84 (0.61, 1.18) | |||
| Cigarettes per day | 0.730 | |||||||
| 0 | 276 | (94.2) | 1112 | (95.6) | Ref | |||
| ≥ 1 | 17 | (5.8) | 51 | (4.4) | 1.11 (0.60, 2.03) | |||
| Vaginal sex acts in the last 7 days | 0.539 | |||||||
| No | 104 | (35.5) | 330 | (28.4) | Ref | |||
| Yes | 189 | (64.5) | 833 | (71.6) | 1.09 (0.82, 1.45) | |||
| Has a primary partner | < 0.001 | |||||||
| No | 25 | (8.5) | 32 | (2.8) | Ref | |||
| Yes | 268 | (91.5) | 1131 | (97.2) | 3.68 (2.12, 6.38) | |||
| Primary partner knows participant is taking part in the study | ||||||||
| No/Unsure | 78 | (26.6) | 241 | (20.7) | Ref | < 0.001 | ||
| Yes | 190 | (64.8) | 890 | (76.5) | 1.54 (1.12, 2.11) | |||
| No primary partner | 25 | (8.5) | 32 | (2.8) | 0.38 (0.21, 0.68) | |||
| Primary partner knows participant was offered the ring (*) | < 0.001 | < 0.001 | ||||||
| No/Unsure | 105 | (35.8) | 342 | (29.4) | Ref | 2.70 (1.39, 5.25) | ||
| Yes | 163 | (55.6) | 789 | (67.8) | 1.53 (1.15, 2.04) | 4.06 (2.14, 7.71) | ||
| No primary partner | 25 | (8.5) | 32 | (2.8) | 0.36 (0.20, 0.64) | Ref | ||
| Number of sexual partners other than primary | 0.970 | |||||||
| 0 | 237 | (80.9) | 947 | (81.4) | Ref | |||
| ≥ 1 | 56 | (19.1) | 216 | (18.6) | 0.99 (0.70, 1.41) | |||
| Anal sex in past 3 months | 0.582 | |||||||
| No | 265 | (90.4) | 1083 | (93.8) | Ref | |||
| Yes | 28 | (9.6) | 71 | (6.2) | 0.88 (0.54, 1.41) | |||
| HIV risk perception | 0.029 | 0.018 | ||||||
| Not/somewhat worried | 235 | (80.2) | 878 | (75.6) | Ref | Ref | ||
| Very worried | 58 | (19.8) | 284 | (24.4) | 1.43 (1.03, 1.98) | 1.54 (1.08, 2.21) | ||
| Contraceptive method | < 0.001 | |||||||
| Condoms /COC | 73 | (24.9) | 132 | (11.3) | Ref | |||
| Injectable | 115 | (39.2) | 454 | (39.0) | 2.60 (1.79, 3.77) | |||
| Implant | 48 | (16.4) | 297 | (25.5) | 3.01 (1.94, 4.67) | |||
| Intrauterine device | 37 | (12.6) | 228 | (19.6) | 2.88 (1.78, 4.66) | |||
| Sterilization | 20 | (6.8) | 52 | (4.5) | 1.52 (0.81, 2.83) | |||
| Type of contraceptive method | < 0.001 | < 0.001 | ||||||
| Short acting (condom, COC) | 73 | (24.9) | 132 | (11.3) | Ref | Ref | ||
| Long-acting + Sterilization | 220 | (75.1) | 1031 | (88.7) | 2.65 (1.88, 3.73) | 3.03 (2.08, 4.41) | ||
| Perceives the ring offers high protection | 0.124 | |||||||
| No | 73 | (25.2) | 270 | (23.2) | Ref | |||
| Yes | 217 | (74.8) | 893 | (76.8) | 1.28 (0.94, 1.74) | |||
| Covariates reported at the end of ASPIRE follow-up | ||||||||
| Very likely to use the ring if it becomes available | < 0.001 | < 0.001 | ||||||
| No | 101 | (41.6) | 277 | (26.0) | Ref | Ref | ||
| Yes | 142 | (58.4) | 789 | (74.0) | 1.79 (1.33, 2.42) | 1.80 (1.32, 2.46) | ||
| Willing to participate in a future RING study | 0.873 | |||||||
| No | 7 | (2.6) | 31 | (2.8) | Ref | |||
| Yes | 267 | (97.4) | 1085 | (97.2) | 0.93 (0.38, 2.32) | |||
Comparison of covariates between consistent ring acceptors (versus not) throughout HOPE. Odds ratios estimates and robust 95% confidence intervals from univariate logistic regressions adjusted by region and number of visits; p-values obtained from likelihood ratio tests; odds ratios estimates and robust 95% confidence intervals from a multivariable logistic regression.
Reference group was changed for multivariable analysis to better illustrate the positive association with both having a primary partner at enrollment, and him knowing about the ring
In univariable logistic regressions adjusted by region and number of visits, the baseline variables that showed a statistically significant association with being a consistent ring acceptor (at p-value < 0.10) were: higher education level, having a primary partner who knew about the study or about the ring being offered, higher HIV risk perception, type of contraceptive method use, and being very likely to use the ring if it ever becomes available (as reported at the end of ASPIRE). Here, the knowledge of the participant’s primary partner about the study as well as his knowledge about the ring were associated with a higher odd of accepting the ring consistently throughout HOPE. Meanwhile, the odds of being a consistent acceptor for those participants without a primary partner at baseline were significantly smaller than for the participants with primary partner that did not know about the study or didn’t know about the ring.
In the multivariable logistic regression, consistent with all the significant covariates (p-value < 0.10) listed above, we found that the statistically significant associations remained for all the covariates when adjusting for all others, and the size of all the estimated odds ratio slightly increased. Again, the primary partner covariate (a composite of having a primary partner and his knowledge about the ring) held the largest association among all the covariates previously listed. Adjusting for region and number of visits, those with a primary partner at baseline who did not know about the ring were more likely to be consistent acceptors: [OR: 2.70, 95% CI: 1.39–5.25]. Participants with a primary partner who knew about the ring had a much greater association with ring acceptance: [OR: 4.06; 95% CI: 2.14–7.71]. Participants using a long-acting contraceptive method or sterilization at baseline had a significantly elevated odds ratio of being a consistent acceptor, compared to women using a short-acting contraceptive method. [OR:3.03; 95% CI: 2.08–4.41]. Having a secondary level education or higher [OR:1.56; 95% CI: 0.99–2.45] and having a high HIV-risk awareness [OR:1.54; 95% CI: 1.08–2.21] were also associated with being a consistent acceptor, while adjusting for region and number of visits.
Changes in ring acceptance
At enrollment there were 1342 participants that accepted the ring. First, we examined trends in ring acceptance over time. As shown in Fig. 2, the percentage of acceptors decreased linearly over the 9 months of ring dispensation and trends in acceptance did not change when HOPE transitioned from a monthly to a quarterly schedule of ring dispensation.
Fig. 2.
Trends in ring acceptance over time, among women who initially accepted the ring in HOPE (N = 1342 at baseline) Blue vertical arrow indicate Month 3 visit when schedule of ring dispensation transitioned from monthly dispensation of 1 ring (baseline, month 1 and 2) to quarterly dispensation of 3 rings (month 3, 6, 9)
Second, Of the 1342 initial acceptors, 1222 (91.1%) were still in the study at month 9 (the last ring access visit). From these 1222 participants, a total of 148 (12.1%) changed their decision to not accepting the ring at month 9. We explored whether this change was related to change in the primary partner status (from having a primary partner at baseline to not having a primary partner at month 9) and the type of contraceptive method used (from using a long-acting contraceptive method at baseline to a short-lasting or none at month 9).
From the 1222 participants followed until month 9 visit or later, 1175 (96.2%) had a primary partner at baseline and information on their primary partner status at month 9. We based our first sub-analysis on these 1175 women. A total of 27 women reported no primary partner at month 9, seven of whom (25.9%) also changed their ring decision to non-acceptor. Conversely, from the remaining 1148 participants that remained with a primary partner at month 9, only 124 (10.8%) changed their ring decision to non-acceptor. This positive relationship between remaining a ring acceptor at month-9 and having a primary partner was statistically significant (p = 0.031; Table IV).
Table IV.
2 × 2 table describing the association between the change in ring acceptance (from acceptor at baseline to non-acceptor at month 9) and any change in primary partner status and in type of contraceptive method
| Remains ring acceptor at month 9 | Changed to non-acceptor at month 9 | Total | |||
|---|---|---|---|---|---|
|
| |||||
| N | (%) | N | (%) | ||
| Baseline acceptors | 1074 | (87.9) | 148 | (12.1) | 1222 |
| Participants who have a primary partner at baseline | |||||
| Does not have primary partner at month 9 | 20 | (74.1) | 7 | (25.9) | 27 |
| Still has a primary partner at month 9 | 1024 | (89.2) | 124 | (10.8) | 1148 |
| Total | 1044 | (88.9) | 131 | (111) | 1175 |
| Participants who used long-acting contraceptive methods other than sterilization at baseline | |||||
| Uses short-acting (none, condoms, Oral pills) at month 9 | 65 | (75.6) | 21 | (24.4) | 86 |
| Still uses long-acting (implants, IUD, injectable) at month 9 | 849 | (91.5) | 79 | (8.5) | 928 |
| Total | 914 | (90.1) | 100 | (9.9) | 1014 |
Similarly, we included the 1014 (83.0%) participants, from the original 1222, that used a long-acting contraceptive method (excluding sterilization) at baseline and for whom we could determine the contraceptive method used at month 9 in a second sub-analysis. From the 86 participants that changed to a short-acting contraceptive method (or nothing) at month 9 in comparison to baseline, 21 (24.4%) changed their ring decision to non-acceptor; and from the 928 participants that maintained the same type of contraceptive method at both time points, ring decision changed for 79 (8.5%). Here too, we found a significant positive association between participants remaining on long-acting contraceptive methods and ring acceptance at month 9 (p < 0.001, see Table IV).
Discussion
In HOPE, an open-label, prospective trial among ring-experienced women who were offered access to the ring for one additional year, we found that the overwhelming majority (92.2%) accepted the ring at baseline and most (79.9%) consistently accepted the ring(s) at all visits. Furthermore, transitioning from a monthly dispensation to a quarterly dispensation schedule didn’t negatively affect ring acceptance trends.
Participants reporting at baseline of having a primary partner who knew of the ring being offered in HOPE, those using a long-acting contraceptive method/sterilization, and those indicating a higher likelihood of using the ring if it becomes available in the future were more likely to initially accept the ring and to consistently accept it throughout the study. In addition, perception that the ring offers high protection from HIV was associated with initial ring acceptance and high HIV risk perception and higher educational attainment were associated with consistent acceptance of the ring.
Although women in HOPE were experienced ring users (from their prior participation in ASPIRE), our findings provide important insight to future programmatic rollout of the ring since the HOPE study assessed ring uptake in the context of choice of other HIV prevention methods and with known efficacy of the ring. Acceptance was defined here as women’s consent to receive the ring (an observable and measurable behavior). Our definition of acceptance -or uptake- aligns with the PrEP “end-user journey” perspective [23, 24], and is narrower than how uptake is typically defined in contraceptive research, as we sought to conceptually separate acceptance (consent, choice or decision to use) from adherence to product use (which include initiation -starting to use-, execution and persistence, as described by Blashke et al.,2012 [25]. Thus, acceptance is a pre-requisite step in the user journey before initiating use and adhering to an intervention. Importantly, when health interventions are not well aligned with users preferences and needs, this can result in poor uptake and low adherence [26]. Since most women consented to receive the ring in HOPE when offered in the context of combination prevention, and the ring was used with higher adherence than in ASPIRE[12], the ring may effectively contribute to decreasing the incidence of HIV through increased overall prevention coverage in the future [27]. Notably, in the crossover MTN034/REACH trial, of the 227(92%) young women who reached the choice period, more than two thirds chose to use the ring[28]. Other acceptability and preference studies for HIV prevention or multipurpose prevention (against HIV and unintended pregnancy), found that rings were an acceptable option that some women were interested in using in the future [29–32].
The high, consistent acceptance of the ring in this analysis aligns well with reported high ring use and persistence in HOPE [12] and compares favorably to acceptance (and persistence) among oral PrEP users in other settings [33, 34]. We observed modest linear decline in ring acceptance over time, but no negative effect from changing from a monthly to a quarterly ring dispensation schedule. This has important implications for future programmatic rollout as less frequent product resupply may minimize burden on the health care system and on the users. Our findings suggest a considerable difference in the probability of acceptance of the ring both initially and consistently over time, between women with a primary partner, particularly when the primary partner was aware of the option to use the ring by participants. We also found a positive relationship between remaining a ring acceptor and not changing the primary partner status. Our results align with those from the ASPIRE trial that found that primary partner knowledge of ring use and keeping a primary partner over time had a positive association with ring adherence [35]. This association could imply that women in committed relationships may feel more stability and security in their sexual encounters to allow for disclosure of ring use to their partner, and thus were able to use the product without fear of social harm [36]. From previous studies, we know that partner awareness of HIV prevention method use, like oral PrEP, is a facilitator to oral PrEP acceptance and persistence [36]. Our findings suggest that the ring could be a preferred preventive method for those in committed relationships where prevention method disclosure can be supported and encouraged.
The use of long-acting contraceptive methods (such as implant, IUD, injectable) and being sterilized was also associated with a higher probability of ring acceptance at baseline and being a consistent acceptor throughout the study[35]. Since HOPE required women to not be pregnant at enrolment and discontinue the ring if confirmed to be pregnant during the study, participants who had intentions to get pregnant may have opted for short-acting contraceptive methods and at the same time decided to stop using the ring in case of pregnancy. The ongoing MTN-042/DELIVER trial may provide more information on safety and acceptability of use of the ring among pregnant women.
Perceived high protection from the ring was associated with initial acceptance of the ring but not consistent acceptance. Notably, many HOPE participants did not remember exact efficacy level either due to lack of memory or comprehension and thus there is a need to find better ways to communicate about partial efficacy of HIV prevention products to women in sub-Saharan Africa [37].
The estimated odds of both accepting the ring at enrollment and being a consistent acceptor for women who reported to be very likely to use the ring in the future, as reported at the exit of the ASPIRE trial, were almost double the odds among women who expressed less certainty about future ring use. The HOPE study provided choice for women to use the ring and data on ring efficacy was available to participants when they enrolled. This knowledge may have facilitated ring acceptance for those who had reported intention for future use in ASPIRE [9]. The link between intentions and actual behavior has been criticized as somewhat tenuous; however, in this study, prior strong intentions to use the ring clearly predicted ring acceptance in HOPE. This was the case despite the 12 months between the end of ASPIRE and enrollment in HOPE [12]. This finding may encourage interventionists to retain questions about intention to use in future studies, as a way to predict both uptake of and engagement with (in the sense of acceptance of the product) a biomedical prevention strategy. Our findings also enhance the credibility of questions related to future intention to use.
Additionally, we found evidence that women who initially accepted the ring, but at month 9 changed either the type of contraceptive method or their relationship status, were significantly more likely to decline the ring at month 9. A woman that was in a committed relationship and is now single might not feel the same need to use a continuous method like the ring as they may no longer perceive themselves be at risk of HIV infection. Also, women changing from a long-acting contraceptive method to a short-acting contraceptive method might intend to get pregnant, and therefore might prefer to stop using the ring. These results suggest that in the future, when the ring becomes available for use in the general population, it might be important for providers to reassess the level of interest with ring use for clients who experience a change in intimate relationships or who decide to change their contraceptive method, until information on safety of ring use during pregnancy becomes available.
The strengths of our study include a multisite design and a large sample size from different geographic, social and economic backgrounds.
Our study had a number of limitations. By design, HOPE enrolled women who were ring-experienced through participation in the ASPIRE trial and therefore the results cannot be generalized to a ring-naïve population. Indeed, initial interest tends to be low for unfamiliar methods like the ring, but there is a learning curve and ring acceptability increases with familiarity and use experience [38, 39]. Also, there could be some self-selection bias—women who joined HOPE may have been more likely to be interested in the ring and to think of it as highly effective. Importantly, HOPE participants were counselled regularly on available and effective HIV prevention options using a standardized “options” counseling approach, but we cannot totally rule out this bias[22]. Also, we do not know if acceptance meant the ring was actually and correctly used, but as a simple observable behavior, acceptance is a reasonable proxy, especially when considering that the objective measure of adherence, residual drug levels in used rings, was high in HOPE [40]. We found that primary partners played a role in women’s likelihood of accepting the ring. However, the partner’s knowledge of woman’s ring use was based off participant self-report; the study did not interview the male partners directly. Finally, while HOPE provided important insights outside of a RCT on ring acceptance and use, we need to further understand ring uptake/acceptance and use in a real world setting among ring naïve women, which can be done through future demonstration projects.
Conclusion
Initial and consistent acceptance of the dapivirine vaginal ring was high in HOPE, and this was not impacted by transitioning to less frequent clinic visits and quarterly dispensation of rings. Being in a stable relationship with a primary partner aware of a woman’s option to use the ring was a strong predictor of initial and consistent ring acceptance, highlighting the key influencing role of intimate partners in HIV prevention. Conversely, short acting contraception was correlated with non-acceptance of the ring, suggesting that declining the ring may be associated with fertility intentions. Future efforts should consider these factors when targeting populations for ring rollout and in designing counseling messages.
Acknowledgments
The authors would like to acknowledge the full MTN-025/HOPE study team and HOPE study participants, without which this work would not have been possible. The vaginal rings used in this study were developed and supplied by the International Partnership for Microbicides (IPM). Data management was provided by the Statistical Center for HIV/AIDS Research & Prevention (Fred Hutchinson Cancer Research Center, Seattle, WA). Site laboratory oversight was provided by the Microbicide Trials Network Laboratory Center (Pittsburgh, PA). Study Team Leadership: Jared Baeten, University of Washington (Protocol Chair); Thesla Palanee-Phillips, Wits Reproductive Health and HIV Institute (Protocol Co-chair); Nyaradzo Mgodi, Zimbabwe, Harare, University of Zimbabwe College of Health Sciences Clinical Trials Unit(Protocol Co-chair) Elizabeth Brown, Fred Hutchinson Cancer Research Center (Protocol Statistician); Lydia Soto-Torres, US National Institute of Allergy and Infectious Diseases (Medical Officer); Ashley Mayo, FHI 360 (Clinical Research Manager). Study sites and site Investigators of Record: Malawi, Blantyre site (Johns Hopkins University, Queen Elizabeth Hospital): Bonus Makanani; Malawi, Lilongwe site (University of North Carolina, Chapel Hill): Lameck Chinula; South Africa, Cape Town site (University of Cape Town): Gonasagrie Nair; South Africa, Durban – Botha’s Hill, Chatsworth, Isipingo, Tongaat, Umkomaas, Verulam sites (South African Medical Research Council): Gita Ramjee, Logashvari Naidoo, Dishiki Kalonji, Samantha Siva, Nishanta Singh; South Africa, Durban, eThekwini site (Center for the AIDS Programme for Research in South Africa):Leila Mansoor; South Africa, Johannesburg site (Wits RHI): Thesla Palanee-Phillips; Uganda, Kampala site (John Hopkins University, Makerere University): Brenda Mirembe; Zimbabwe, Chitungwiza and Harare—Zengeza, Seke South and Splihaus sites (University of Zimbabwe Clinical Trials Research Centre (UZ-CTRC): Nyaradzo Mgodi, Portia Hunidzarira, and Felix Mhlanga.
Funding
The study was designed and implemented by the Microbicide Trials Network (MTN) and funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The vaginal rings used in this study were supplied by the International Partnership for Microbicides (IPM).
Footnotes
Declarations
Conflicts of interest/Competing interests The authors have no relevant financial or non-financial interests to disclose.
Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the following Institutional Review Boards/Ethics Committees and Drug Regulatory Authorities: Prevention Sciences Research Committee of the US National Institute of Allergy and Infectious Diseases; US Food and Drug Administration; National Health Sciences Research Committee of Malawi; Johns Hopkins University Bloomberg School of Public Health Institutional Review Board; University of North Carolina at Chapel Hill Institutional Review Board; Pharmacy, Medicines and Poisons Board of Malawi; University of Cape Town: Human Research Ethics Committee; Biomedical Research Ethics Committee University of KwaZulu-Natal; South African Medical Research Council Ethics Committee; Human Research Ethics Committee: (Medical), University of Witwatersrand, Johannesburg; Medicines Control Council of South Africa; Joint Clinical Research Centre Institutional Review Board; Uganda National Council for Science and Technology; Johns Hopkins University School of Medicine Institutional Review Board; National Drug Authority of Uganda; Medical Research Council of Zimbabwe; Committee on Human Research, University of California - San Francisco; Joint Parirenyatwa Hospital and College of Health Sciences Research Ethics; Research Council of Zimbabwe; Medicines Control Authority of Zimbabwe.
Consent to participate Informed consent was obtained from all individual participants included in the study.
Consent for publication Not applicable.
Code Availability Not applicable.
Data Availability
Not applicable.
References
- 1.UNAIDS. Women and HIV. A spotlight on adolescent girls and young women. 2019.
- 2.Sahay S, et al. , Understanding Issues Around Use of Oral Pre-Exposure Prophylaxis Among Female Sex Workers in India. 2021. [DOI] [PMC free article] [PubMed]
- 3.Gambir K, et al. Opportunities and challenges for the introduction of a new female condom among young adults in urban Zambia. Reproductive health. 2019;16(1):1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Koechlin FM, et al. Values and preferences on the use of oral pre-exposure prophylaxis (PrEP) for HIV prevention among multiple populations: a systematic review of the literature. AIDS Behav. 2017;21(5):1325–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Celum CL, et al. HIV pre-exposure prophylaxis for adolescent girls and young women in Africa: from efficacy trials to delivery. J Int AIDS Soc. 2019;22:e25298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Quaife M, et al. Divergent preferences for HIV prevention: a discrete choice experiment for multipurpose HIV prevention products in South Africa. Med Decis Making. 2018;38(1):120–33. [DOI] [PubMed] [Google Scholar]
- 7.Nel A, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016;375(22):2133–43. [DOI] [PubMed] [Google Scholar]
- 8.Baeten JM, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375(22):2121–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Mayo AJ, et al. , Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial. AIDS and Behavior, 2021: p. 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Montgomery ET, et al. Acceptability and use of a dapivirine vaginal ring in a phase III trial. AIDS. 2017;31(8):1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Brown ER, et al. Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo‐controlled trial. J Int AIDS Soc. 2020;23(11):e25634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Baeten JM, et al. Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study. The Lancet HIV. 2021;8(2):e87–95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Nel A, et al. Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study. The Lancet HIV. 2021;8(2):e77–86. [DOI] [PubMed] [Google Scholar]
- 14.World Health Organisation. European Medicines Agency (EMA) approval of the dapivirine ring for HIV prevention for women in high HIV burden settings. 2021; Available from: https://www.who.int/news/item/24-07-2020-european-medicines-agency-(ema)-approval-of-the-dapivirine-ring-for-hiv-prevention-for-women-in-high-hiv-burden-settings.
- 15.World Health Organisation. WHO recommends the dapivirine vaginal ring as a new choice for HIV prevention for women at substantial risk of HIV infection. 2021; Available from: https://www.who.int/news/item/26-01-2021-who-recommends-the-dapivirine-vaginal-ring-as-a-new-choice-for-hiv-prevention-for-women-at-substantial-risk-of-hiv-infection.
- 16.Fokazi S. More HIV prevention options for SA women as vaginal ring is approved. 2022; Available from: https://www.timeslive.co.za/news/south-africa/2022-03-16-more-hiv-prevention-options-for-sa-women-as-vaginal-ring-approved/.
- 17.Gwarisa M. #BREAKING:Dapivirine, Vaginal Ring approved for use in Zimbabwe. 2021. [cited 2021 27 July]; Available from: https://healthtimes.co.zw/2021/07/14/breaking-dapivirine-vaginal-ring-approved-for-use-in-zimbabwe/.
- 18.Proctor E, et al. Outcomes for implementation research: conceptual distinctions, measurement challenges, and research agenda. Adm policy mental health mental health Serv Res. 2011;38(2):65–76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017;17(1):1–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sekhon M, van der Straten A, Team M-MS. Pregnant and breastfeeding women’s prospective acceptability of two biomedical HIV prevention approaches in Sub Saharan Africa: A multisite qualitative analysis using the Theoretical Framework of Acceptability. PLoS ONE. 2021;16(11):e0259779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Shannon K, Csete J. Violence, condom negotiation, and HIV/STI risk among sex workers. JAMA. 2010;304(5):573–4. [DOI] [PubMed] [Google Scholar]
- 22.Balán IC, et al. Client-centered adherence counseling with adherence measurement feedback to support use of the dapivirine ring in MTN-025 (The HOPE Study). AIDS Behav. 2021;25(2):447–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.O’Rourke S, et al. The PrEP journey: Understanding how internal drivers and external circumstances impact the PrEP trajectory of adolescent girls and young women in Cape Town, South Africa. AIDS Behav. 2021;25(7):2154–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Rousseau E, et al. Novel Platforms for Biomedical HIV Prevention Delivery to Key Populations — Community Mobile Clinics, Peer-Supported, Pharmacy-Led PrEP Delivery, and the Use of Telemedicine. Curr HIV/AIDS Rep. 2021;18(6):500–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Blaschke TF, et al. Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev Pharmacol Toxicol. 2012;52:275–301. [DOI] [PubMed] [Google Scholar]
- 26.Ostermann J, et al. Preferences for health interventions: improving uptake, adherence, and efficiency. The Patient-Patient-Centered Outcomes Research. 2017;10(4):511–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Guest G, et al. Acceptability of PrEP for HIV prevention among women at high risk for HIV. J Women’s Health. 2010;19(4):791–8. [DOI] [PubMed] [Google Scholar]
- 28.Ngure K Choice and Adherence to Dapivirine Ring or Oral PrEP by Young African Women in REACH. 2022; Available from: https://www.natap.org/2022/CROI/croi_90.htm.
- 29.Minnis AM, et al. , Young women’s stated preferences for biomedical HIV prevention: results of a discrete choice experiment in Kenya and South Africa. Journal of acquired immune deficiency syndromes (1999), 2019. 80(4): p. 394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.van der Straten A, et al. The Tablets, Ring, Injections as Options (TRIO) study: what young African women chose and used for future HIV and pregnancy prevention. J Int AIDS Soc. 2018;21(3):e25094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Donnell D, et al. Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study. The Lancet HIV; 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Montgomery ET, et al. End-user preference for and choice of four vaginally delivered HIV prevention methods among young women in South Africa and Zimbabwe: the Quatro Clinical Crossover Study. J Int AIDS Soc. 2019;22(5):e25283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Celum C, et al. PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial. PLoS Med. 2021;18(6):e1003670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Celum CL, et al. Incentives conditioned on tenofovir levels to support PrEP adherence among young South African women: a randomized trial. J Int AIDS Soc. 2020;23(11):e25636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Husnik MJ, et al. Correlates of Adherence to the Dapivirine Vaginal Ring for HIV-1 Prevention. AIDS and Behavior; 2021. pp. 1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Jackson-Gibson M, et al. Facilitators and barriers to HIV pre-exposure prophylaxis (PrEP) uptake through a community-based intervention strategy among adolescent girls and young women in Seme Sub-County, Kisumu, Kenya. BMC Public Health. 2021;21(1):1–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Etima J, et al. , Does the Ring Work? Perceptions and Understanding of the Efficacy of a Dapivirine Vaginal Ring for HIV Prevention Amongst Women in a Placebo-Controlled Trial. AIDS and Behavior, 2021: p. 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Griffin JB, et al. Vaginal ring acceptability and related preferences among women in low-and middle-income countries: a systematic review and narrative synthesis. PLoS ONE. 2019;14(11):e0224898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Ridgeway K, et al. , Vaginal ring acceptability: a systematic review and meta-analysis of vaginal ring experiences from around the world. Contraception, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Bekker L-G, et al. HPTN 067/ADAPT Cape Town: a comparison of daily and nondaily PrEP dosing in African women. in Conference on Retroviruses and Opportunistic Infections. 2015. [Google Scholar]
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Data Availability Statement
Not applicable.