The Experts below are selected from a list of 3819 Experts worldwide ranked by ideXlab platform
Jeffrey T Jensen - One of the best experts on this subject based on the ideXlab platform.
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a technology evaluation of annovera a segesterone acetate and ethinyl estradiol Vaginal Ring used to prevent pregnancy for up to one year
Expert Opinion on Drug Delivery, 2020Co-Authors: Elizabeth Micks, Jeffrey T JensenAbstract:Introduction: The segesterone acetate and ethinyl estradiol contraceptive Vaginal Ring (SA/EE CVR) was FDA-approved in August 2018 and is now available in the U.S. The CVR is placed Vaginally for 2...
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evaluating the efficacy and safety of a progestin and estrogen releasing ethylene vinyl acetate copolymer contraceptive Vaginal Ring
Expert Opinion on Drug Safety, 2014Co-Authors: Brian T Nguyen, Jeffrey T JensenAbstract:INTRODUCTION: Multiple studies confirm the safety and efficacy of the combined ethinyl estradiol (EE) and etonogestrel contraceptive Vaginal Ring (NuvaRing®). Advantages of continuous drug delivery through the vagina compared to oral administration include stable levels of contraceptive steroids without the need for daily drug administration. Although the combined contraceptive Vaginal Ring (CCVR) avoids the problem of missed pills, clinical data do not support greater efficacy. Vaginal administration avoids first-pass hepatic effects; however, EE is a potent inducer of hepatic globulins regardless of the route of administration. Consequently, thromboembolic risk duRing CCVR use is similar to that with combined oral contraceptives. Some epidemiologic and database studies suggest that the risk of thromboembolism is increased among users of the CCVR compared to levonorgestrel-containing combined pills. AREAS COVERED: This review examined the available literature for level 1 and level 2 evidence of the CCVR and its associated efficacy and safety. Studies are presented in table format with significant findings and conclusions described. EXPERT OPINION: A prospective study with 33,235 woman-years of exposure and with greater ability to control for covariates did not demonstrate an elevation of risk. The safety profile of the CCVR appears to be the same as with other combined hormonal contraceptives.
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Vaginal Ring delivery of selective progesterone receptor modulators for contraception
Contraception, 2013Co-Authors: Jeffrey T JensenAbstract:Abstract Vaginal Ring delivery of selective progesterone receptor modulators (SPRMs) is under development to address the limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive Vaginal Ring (CVR) also eliminates the need for daily dosing and therefore might improve the effectiveness of contraception. The principal contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate (UPA) is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a Ring designed for continuous use over 3 months deliveRing near steady-state drug levels that will suppress ovulation. Results from Phase 1 and 2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL.
Ariane Van Der Straten - One of the best experts on this subject based on the ideXlab platform.
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brief report anal intercourse hiv 1 risk and efficacy in a trial of a dapivirine Vaginal Ring for hiv 1 prevention
Journal of Acquired Immune Deficiency Syndromes, 2020Co-Authors: Kathryn Peebles, Krishnaveni Reddy, Nitesha Jeenarain, Thesla Palaneephillips, Ariane Van Der Straten, Ishana Harkoo, Sharon L Hillier, Craig W Hendrix, Brenda Gati Mirembe, Jared M BaetenAbstract:OBJECTIVES: To describe receptive anal intercourse (RAI) behaviors and correlates in a cohort of sub-Saharan African women, evaluate the association of RAI with HIV-1 risk, and evaluate whether the HIV-1 prevention efficacy of a dapivirine-containing Vaginal Ring differs among women who reported RAI. DESIGN: Secondary analysis of the MTN-020/ASPIRE trial, a randomized, double-blind, placebo-controlled trial evaluating a dapivirine-containing Vaginal Ring for HIV-1 prevention. METHODS: At enrollment and month three, women reported RAI in the prior three months in audio computer-assisted self-interviews. We evaluated associations between RAI and participant characteristics with chi-square and t-tests adjusted for study site. Cox proportional hazards models stratified by study site tested the association of RAI with HIV-1 acquisition and effect modification by RAI. RESULTS: Nineteen percent of women reported any RAI at enrollment and/or month 3, with a median of 2 (IQR: 1, 4) RAI acts in the prior three months, accounting for 1.5% of total sex acts. RAI prevalence was higher among women with lower educational attainment and those reporting transactional sex. In adjusted models, RAI was not associated with HIV-1 acquisition (aHR: 0.93, 95% CI: 0.57, 1.54). The Ring reduced HIV-1 risk by 27% (95% CI: -5, 49) among women reporting no RAI and by 18% (95% CI: -57, 57) among women reporting any RAI (interaction p-value=0.77). CONCLUSIONS: RAI was modestly infrequent and was not associated with reduced HIV-1 protection from the Ring, suggesting that, in populations with rates of RAI similar to this cohort, RAI may not appreciably reduce the population-level impact of the dapivirine Vaginal Ring.
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hygiene blood flow and Vaginal overload why women removed an hiv prevention Vaginal Ring duRing menstruation in malawi south africa uganda and zimbabwe
Aids and Behavior, 2020Co-Authors: Zoe Duby, Krishnaveni Reddy, Ariana Katz, Juliane Etima, Erica N Browne, Prisca Mutero, Chifundo Colleta Zimba, Kubashni Woeber, Millicent Atujuna, Ariane Van Der StratenAbstract:: We assessed the interference between Vaginal Ring use and menses among women who participated in the qualitative component of the MTN-020/ASPIRE Vaginal Ring trial in Malawi, South Africa, Uganda and Zimbabwe (N = 214). A common reason for imperfect Ring adherence and premature removal of the Vaginal Ring cited by participants related to Vaginal bleeding or menses. Whereas self-reporting via survey questions suggested that the majority (60%) of women did not mind weaRing the Ring while menstruating, and did not remove it (91%) duRing menses, in the qualitative interviews women frequently described removing the Ring duRing menses. Their reasons included hygiene, beliefs that the Ring blocked the flow of menstrual blood, fears that the Ring would come out with blood or duRing tampon removal, and concerns around an 'overburdened' vagina. Examining women's narratives and subjective experiences related to menstruation helps build a better understanding of factors affecting Ring use and adherence.
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first impressions matter how initial worries influence adherence to the dapivirine Vaginal Ring
Journal of Acquired Immune Deficiency Syndromes, 2019Co-Authors: Ariane Van Der Straten, Krishnaveni Reddy, Elizabeth R Brown, Thesla Palaneephillips, Erica N Browne, Mary Kate Shapleyquinn, Rachel Scheckter, Lydia Sototorres, Jared M Baeten, Barbara S MenschAbstract: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 rin
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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
PLOS ONE, 2016Co-Authors: Lindagail Bekker, Gileard Masenga, Elizabeth T Montgomery, Elizabeth A Bukusi, Elizabeth Hellstrӧm, Philip Kotze, Cheryl Louw, Francis Martinson, Nelisiwe Ndaba, Ariane Van Der StratenAbstract:Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing Vaginal Ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered Vaginal Ring containing the antiretroviral microbicide, dapivirine, with a matching placebo Ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine Vaginal Ring (25 mg) and 140 women to a matching placebo Ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned Rings from dapivirine Ring users were determined post-trial. Participant acceptability and adherence to Ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo Ring groups. Plasma dapivirine concentrations immediately prior to Ring removal were similar after removal of the first and third Ring, suggesting consistent Ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used Rings and corresponding plasma concentrations. Self-reported adherence to daily use of the Vaginal Rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the Ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine Vaginal Ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. Trial Registration ClinicalTrials.gov NCT01071174
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adherence and acceptability of a multidrug Vaginal Ring for hiv prevention in a phase i study in the united states
Aids and Behavior, 2016Co-Authors: Ariane Van Der Straten, Lydia Sototorres, Nicole Laborde, Lori Panther, Craig J Hoesley, Helen Cheng, Marla Husnik, Stephanie Horn, Beatrice A ChenAbstract:We evaluated the adherence and acceptability of a Vaginal Ring containing dapivirine, maraviroc, or both drugs for 28 days duRing a Phase I placebo-controlled trial in 48 HIV-negative sexually abstinent U.S. women aged 18–40. Adherence was assessed weekly by clinical interview and computer-assisted self-interviewing; acceptability assessment occurred at the last product-use visit. Study retention was 98 % (47/48); 94 % (45/48) reported being fully adherent with Ring use duRing the 28-day period. Two participants experienced the Ring partially coming out. Analysis was blinded and behavioral data were combined across study groups. Most women reported being very comfortable having the Ring in their vagina; 44 % preferred continuous use, whereas 51 % had no preference compared to episodic use. Although a range of minor Ring concerns were expressed, few were actually experienced. High adherence to and acceptability of this Vaginal Ring in this Phase I trial contributes to its promise as a sustained mechanism for multidrug Vaginal microbicide delivery.
Kenneth F Schulz - One of the best experts on this subject based on the ideXlab platform.
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skin patch and Vaginal Ring versus combined oral contraceptives for contraception
Cochrane Database of Systematic Reviews, 2013Co-Authors: Laureen M Lopez, David A Grimes, Maria F Gallo, Laurie L Stockton, Kenneth F SchulzAbstract:BACKGROUND: The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive Vaginal Ring offers potential advantages over the traditional oral route. The transdermal patch and Vaginal Ring could require a lower dose due to increased bioavailability and improved user compliance. OBJECTIVES: To compare the contraceptive effectiveness cycle control compliance (adherence) and safety of the contraceptive patch or the Vaginal Ring versus combination oral contraceptives (COCs). SEARCH METHODS: Through February 2013 we searched MEDLINE POPLINE CENTRAL LILACS ClinicalTrials.gov and ICTRP for trials of the contraceptive patch or the Vaginal Ring. Earlier searches also included EMBASE. For the initial review we contacted known researchers and manufacturers to identify other trials. SELECTION CRITERIA: We considered randomized controlled trials compaRing a transdermal contraceptive patch or a contraceptive Vaginal Ring with a COC. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. For dichotomous variables the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables the mean difference was computed. We also assessed the quality of evidence for this review. MAIN RESULTS: We found 18 trials that met our inclusion criteria. Of six patch studies five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 Vaginal Ring trials 11 examined the same marketing Ring containing etonogestrel plus EE; one studied a Ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or Ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four Vaginal Ring trials one found Ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52) while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort dysmenorrhea nausea and vomiting. In the levonorgestrel-containing patch trial patch users reported less vomiting headaches and fatigue.Of 11 Ring trials with discontinuation data two showed the Ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users Ring users had more vaginitis and leukorrhea but less Vaginal dryness. Ring users also reported less nausea acne irritability depression and emotional lability than COC users.For cycle control only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven Ring studies had bleeding data; four trials showed the Ring group generally had better cycle control than the COC group. AUTHORS CONCLUSIONS: Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of Ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the Ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more Vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the Ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment the outcome assessment methods high losses to follow up and exclusions after randomization.
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Skin patch and Vaginal Ring versus combined oral contraceptives for contraception.
The Cochrane database of systematic reviews, 2010Co-Authors: Laureen M Lopez, David A Grimes, Maria F Gallo, Kenneth F SchulzAbstract:The delivery of combination contraceptive steroids from a skin patch or Vaginal Ring offers potential advantages over the traditional oral route. The skin patch and Vaginal Ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, adherence (compliance), and safety of the skin patch or the Vaginal Ring versus combination oral contraceptives (COCs). For trials of the contraceptive patch or the Vaginal Ring, we searched MEDLINE, POPLINE, CENTRAL, EMBASE, LILACS, ClinicalTrials.gov, and ICTRP. We contacted manufacturers and researchers to identify other trials. All randomized controlled trials compaRing the skin patch or Vaginal Ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We found 5 trials of the skin patch and 10 of the Vaginal Ring. Contraceptive effectiveness was similar for the patch or Ring versus the comparison COC. More patch users discontinued early than COC users: ORs were 1.59 (95% CI 1.26 to 2.00), 1.56 (95% CI 1.18 to 2.06), and 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events. Compared to COC users, patch users reported more breast discomfort, dysmenorrhea, nausea, and vomiting. Patch users reported more compliant cycles than the COC users in two trials: ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). The Ring trials generally showed similar discontinuation for Ring and COC users. Ring users reported less nausea, acne, irritability, and depression than COC users. Ring users had more vaginitis and leukorrhea but less Vaginal dryness. Ring users had similar adherence to COC users in two trials but less adherence in one. Cycle control was generally similar for the patch and COC, and was similar or better for the Ring versus COC. Effectiveness was similar for the methods compared. The patch could lead to more discontinuation while the Vaginal Ring showed little difference. The patch group had better compliance than the COC group but more side effects. Ring users generally had fewer adverse events than COC users but more Vaginal irritation and discharge. High losses to follow up can affect the validity of the results.
Krishnaveni Reddy - One of the best experts on this subject based on the ideXlab platform.
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use of the dapivirine Vaginal Ring and effect on cervical cytology abnormalities
AIDS, 2020Co-Authors: Krishnaveni Reddy, Cliff Kelly, Elizabeth R Brown, Nitesha Jeenarain, Logashvari Naidoo, Samantha Siva, Lindagail Bekker, Gonasagrie Nair, Bonus MakananiAbstract:Objective We aimed to determine if the dapivirine Vaginal Ring and the Ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities. Design Secondary analysis compaRing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE). Methods Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine Vaginal Ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo Vaginal Ring. We further assessed for the effect of the Vaginal Ring device on cervical cytology by compaRing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population. Results Cervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo Vaginal Ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo Vaginal Ring arms (P = 0.24). Conclusion These findings indicate that neither use of the dapivirine Vaginal Ring nor the Vaginal Ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.
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brief report anal intercourse hiv 1 risk and efficacy in a trial of a dapivirine Vaginal Ring for hiv 1 prevention
Journal of Acquired Immune Deficiency Syndromes, 2020Co-Authors: Kathryn Peebles, Krishnaveni Reddy, Nitesha Jeenarain, Thesla Palaneephillips, Ariane Van Der Straten, Ishana Harkoo, Sharon L Hillier, Craig W Hendrix, Brenda Gati Mirembe, Jared M BaetenAbstract:OBJECTIVES: To describe receptive anal intercourse (RAI) behaviors and correlates in a cohort of sub-Saharan African women, evaluate the association of RAI with HIV-1 risk, and evaluate whether the HIV-1 prevention efficacy of a dapivirine-containing Vaginal Ring differs among women who reported RAI. DESIGN: Secondary analysis of the MTN-020/ASPIRE trial, a randomized, double-blind, placebo-controlled trial evaluating a dapivirine-containing Vaginal Ring for HIV-1 prevention. METHODS: At enrollment and month three, women reported RAI in the prior three months in audio computer-assisted self-interviews. We evaluated associations between RAI and participant characteristics with chi-square and t-tests adjusted for study site. Cox proportional hazards models stratified by study site tested the association of RAI with HIV-1 acquisition and effect modification by RAI. RESULTS: Nineteen percent of women reported any RAI at enrollment and/or month 3, with a median of 2 (IQR: 1, 4) RAI acts in the prior three months, accounting for 1.5% of total sex acts. RAI prevalence was higher among women with lower educational attainment and those reporting transactional sex. In adjusted models, RAI was not associated with HIV-1 acquisition (aHR: 0.93, 95% CI: 0.57, 1.54). The Ring reduced HIV-1 risk by 27% (95% CI: -5, 49) among women reporting no RAI and by 18% (95% CI: -57, 57) among women reporting any RAI (interaction p-value=0.77). CONCLUSIONS: RAI was modestly infrequent and was not associated with reduced HIV-1 protection from the Ring, suggesting that, in populations with rates of RAI similar to this cohort, RAI may not appreciably reduce the population-level impact of the dapivirine Vaginal Ring.
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hygiene blood flow and Vaginal overload why women removed an hiv prevention Vaginal Ring duRing menstruation in malawi south africa uganda and zimbabwe
Aids and Behavior, 2020Co-Authors: Zoe Duby, Krishnaveni Reddy, Ariana Katz, Juliane Etima, Erica N Browne, Prisca Mutero, Chifundo Colleta Zimba, Kubashni Woeber, Millicent Atujuna, Ariane Van Der StratenAbstract:: We assessed the interference between Vaginal Ring use and menses among women who participated in the qualitative component of the MTN-020/ASPIRE Vaginal Ring trial in Malawi, South Africa, Uganda and Zimbabwe (N = 214). A common reason for imperfect Ring adherence and premature removal of the Vaginal Ring cited by participants related to Vaginal bleeding or menses. Whereas self-reporting via survey questions suggested that the majority (60%) of women did not mind weaRing the Ring while menstruating, and did not remove it (91%) duRing menses, in the qualitative interviews women frequently described removing the Ring duRing menses. Their reasons included hygiene, beliefs that the Ring blocked the flow of menstrual blood, fears that the Ring would come out with blood or duRing tampon removal, and concerns around an 'overburdened' vagina. Examining women's narratives and subjective experiences related to menstruation helps build a better understanding of factors affecting Ring use and adherence.
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first impressions matter how initial worries influence adherence to the dapivirine Vaginal Ring
Journal of Acquired Immune Deficiency Syndromes, 2019Co-Authors: Ariane Van Der Straten, Krishnaveni Reddy, Elizabeth R Brown, Thesla Palaneephillips, Erica N Browne, Mary Kate Shapleyquinn, Rachel Scheckter, Lydia Sototorres, Jared M Baeten, Barbara S MenschAbstract: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 rin
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negative rumours about a Vaginal Ring for hiv 1 prevention in sub saharan africa
Culture Health & Sexuality, 2019Co-Authors: Miria Chitukuta, Krishnaveni Reddy, Zoe Duby, Ariana Katz, Teopista Nakyanzi, Thesla Palaneephillips, Tchangani Tembo, Juliane Etima, Petina Musara, Nyaradzo MgodiAbstract:Rumours may influence health-related behaviours, including the uptake of and adherence to HIV prevention products. This study assessed the safety and effectiveness of a Vaginal Ring deliveRing the ...
Lindagail Bekker - One of the best experts on this subject based on the ideXlab platform.
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use of the dapivirine Vaginal Ring and effect on cervical cytology abnormalities
AIDS, 2020Co-Authors: Krishnaveni Reddy, Cliff Kelly, Elizabeth R Brown, Nitesha Jeenarain, Logashvari Naidoo, Samantha Siva, Lindagail Bekker, Gonasagrie Nair, Bonus MakananiAbstract:Objective We aimed to determine if the dapivirine Vaginal Ring and the Ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities. Design Secondary analysis compaRing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE). Methods Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine Vaginal Ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo Vaginal Ring. We further assessed for the effect of the Vaginal Ring device on cervical cytology by compaRing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population. Results Cervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo Vaginal Ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo Vaginal Ring arms (P = 0.24). Conclusion These findings indicate that neither use of the dapivirine Vaginal Ring nor the Vaginal Ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.
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safety of a silicone elastomer Vaginal Ring as potential microbicide delivery method in african women a phase 1 randomized trial
PLOS ONE, 2018Co-Authors: Janine Martins, Lindagail Bekker, Gita Ramjee, Gileard Masenga, Helen Rees, Neliëtte Van NiekerkAbstract:Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal Rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with Vaginal Rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo Vaginal Ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo Vaginal Ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo Vaginal Ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuRing no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed duRing the trial. No serious adverse events were reported considered related to the placebo Vaginal Ring. Vaginal candidiasis was the most common adverse event occurRing in 11% of participants duRing each trial period. Vaginal discharge (2%), Vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the Vaginal Ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive duRing the trial. Conclusions The silicone elastomer Vaginal Ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.
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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
PLOS ONE, 2016Co-Authors: Lindagail Bekker, Gileard Masenga, Elizabeth T Montgomery, Elizabeth A Bukusi, Elizabeth Hellstrӧm, Philip Kotze, Cheryl Louw, Francis Martinson, Nelisiwe Ndaba, Ariane Van Der StratenAbstract:Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing Vaginal Ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered Vaginal Ring containing the antiretroviral microbicide, dapivirine, with a matching placebo Ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine Vaginal Ring (25 mg) and 140 women to a matching placebo Ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned Rings from dapivirine Ring users were determined post-trial. Participant acceptability and adherence to Ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo Ring groups. Plasma dapivirine concentrations immediately prior to Ring removal were similar after removal of the first and third Ring, suggesting consistent Ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used Rings and corresponding plasma concentrations. Self-reported adherence to daily use of the Vaginal Rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the Ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine Vaginal Ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. Trial Registration ClinicalTrials.gov NCT01071174
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characteristics of women enrolled into a randomized clinical trial of dapivirine Vaginal Ring for hiv 1 prevention
PLOS ONE, 2015Co-Authors: Thesla Palaneephillips, Elizabeth R Brown, Samantha Siva, Gonasagrie Nair, Nyaradzo Mgodi, Flavia Matovu Kiweewa, Katie Schwartz, Vaneshree Govender, Felix Mhlanga, Lindagail BekkerAbstract:INTRODUCTION: Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing Vaginal microbicide Rings which release medication over a month or longer may reduce these adherence challenges. METHODS: ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III randomized double-blind placebo-controlled trial testing the safety and effectiveness of a Vaginal Ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. RESULTS: Between August 2012 and June 2014 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi South Africa Uganda and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned Vaginal Ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis 7% Trichomonas Vaginalis 4% Neisseria gonorrhoeae and 1% syphilis. CONCLUSIONS: African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine Vaginal Ring for HIV-1 prevention.
