MTN-045 – A qualitative study that enrolled 400 couples in Uganda and Zimbabwe to understand their views of and preferences for dual-purpose products that could feasibly prevent both unintended pregnancy and HIV infection. The study, which was conducted in 2020, will help inform the design and delivery of dual-purpose products, and sheds important light on the role male partners play in the decision-making process.
MTN-044/IPM 053/CCN019 – A Phase I study of a 90-day vaginal ring containing the antiretroviral drug dapivirine (200 mg) and the contraceptive hormone levonorgestrel (320 mg). Results, which were reported in 2021, found the ring delivered sustained levels of each drug when used continuously for 90 days – levels likely sufficient to serve its dual purpose for protecting against both HIV and unwanted pregnancy – and no significant safety concerns. Because irregular bleeding is a common side effect of progestin-only contraceptives, the study looked to see if removing the ring for a few days each month, as is commonly done for other contraceptives, would reduce or eliminate irregular bleeding. The study found no differences in bleeding patterns between women who used the ring continuously for 90 days and those who used it cyclically (three cycles during which the ring was used for 28 days and removed for two days). Of concern, however, was that a number of participants reported the ring coming out on its own, either partially or completely, a finding that resulted in the ring being reformulated. (See also MTN-030/IPM 041.) Results and more info…
MTN-042B – Was designed and conducted as sub-study of DELIVER (MTN-042) to provide the basis for comparison needed to evaluate the safety of oral PrEP and the dapivirine ring during pregnancy. MTN-042B involved a review of more than 10,000 medical charts at maternity hospitals and clinics in the same communities where DELIVER is taking place, providing important insight about pregnancy and neonatal outcomes in these communities as well as the frequency with which different complications occur. (See also MTN-042/DELIVER.) Results and more info…
MTN-041 – Also known as MAMMA, a qualitative study that took place in Malawi, South Africa, Uganda and Zimbabwe to understand community belief systems and attitudes that may affect women’s perceptions about and potential interest in using the monthly dapivirine vaginal ring or daily oral PrEP during pregnancy and breastfeeding and to help inform implementation of the DELIVER (MTN-042) and B-PROTECTED (MTN-043) studies of these products in pregnant and breastfeeding women, respectively. The study involved group discussions with pregnant and breastfeeding women, male partners and mothers and mothers-in-law of pregnant and breastfeeding women and interviews with community leaders, healthcare providers, midwives and traditional birth attendants, among others. (See also MTN-042/DELIVER and MTN-043/B-PROTECTED). More info…
MTN-039 – A Phase I study launched in late 2019 that was designed to evaluate the safety and acceptability of a fast-dissolving rectal insert containing the antiretroviral drugs tenofovir and elvitegravir, as well as the degree that each drug concentrates in rectal tissue. The study, the first ever of the tenofovir and elvitegravir insert used rectally, enrolled 23 participants at two sites in the U.S. More info…
MTN-038 – A Phase I study of a 90-day vaginal ring containing tenofovir that was developed to protect women against both HIV and herpes simplex virus type 2 (HSV-2). The study assessed the safety of the ring and drug levels in tissue among 49 women at three U.S. trial sites. Results, reported in early 2022, found the ring was well-tolerated and acceptable but that in a subset of participants there was a more rapid release of tenofovir from the ring. More info…
MTN-037 – A Phase I study that evaluated whether a microbicide gel called PC-1005 is safe for use in the rectum. PC-1005 contains an antiretroviral drug called MIV-150; zinc acetate dihydrate, an agent that acts against HSV type 2 (HSV-2); and carrageenan, a potent anti-HIV agent and gellant. The study, which included 12 HIV-negative cisgender and transgender men and women at two sites in the U.S., found the gel was safe and well-tolerated with low systemic MIV-150 exposure. Through tissue sampling, researchers also concluded that a longer-acting formulation or higher dose of MIV-150 would be required to deliver an adequate amount of the drug for it to be effective at preventing the rectal transmission of HIV. Results and more info…
MTN-036/IPM 047 – A Phase I study that evaluated two formulations of a ring designed to slowly release the antiretroviral drug dapivirine in the vagina over the course of 90 days, one containing 100 mg of dapivirine and the other containing 200 mg. Results, which were reported at the Conference on Retroviruses and Opportunistic Infections in 2021, found both formulations were well-tolerated and delivered target levels of drug throughout the three months of use, suggesting they may have the potential to provide long-acting and sustained HIV protection. More info…
MTN-035/DESIRE (Developing and Evaluating Short-acting Innovations for Rectal Use) – An acceptability, tolerability and adherence study of three placebo products for use in the rectum -- a douche, suppository and fast-dissolving rectal insert – to help answer important questions about preferences for rectal microbicide products for the prevention of HIV from anal sex. The products, which contained no active drugs, were evaluated in 217 HIV-negative cisgender men, transgender men and transgender women who have sex with men at sites in Malawi, Peru, South Africa, Thailand and the U.S. Preliminary results, which were reported in 2021, found all three approaches appealing to participants and fitting into their daily lives, underscoring the importance of developing a range of HIV prevention options for people who practice anal sex. Results and more info…
MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) – A Phase IIa trial that was designed to fill important gaps in information about the safety and acceptability of the monthly dapivirine vaginal ring and Truvada® as daily oral pre-exposure prophylaxis (PrEP) in girls younger than 18 and to supplement existing safety and acceptability data of these products in young women ages 18-21. REACH also sought to understand what kind of support adolescent girls and young women need to use these products as best they can and their preferences for either or both. The study, which took place between February 2019 and September 2021 at four trial sites in South Africa, Uganda and Zimbabwe, found adherence to product use was higher than seen in earlier studies, and that compared to oral PrEP, more participants wanted to use the ring. There were no safety concerns with either product. Results and more info…
MTN-033 – A Phase I study that looked at the safety and distribution of dapivirine gel when administered rectally as a lubricant (without an applicator) to determine whether enough drug is delivered in the tissue to feasibly provide HIV protection. The study was conducted in the U.S. and enrolled 16 cisgender men who have sex with men. Results, which were reported in 2021, found higher than expected levels of drug in rectal tissue, but that dapivirine did not remain in tissue long enough to be able to provide sustained protection. (See also MTN-026). Results and more info…
MTN-032 – A qualitative study to better understand what factors influenced women’s use or nonuse of the dapivirine ring during participation in ASPIRE (MTN-020), a placebo-controlled trial, and HOPE (MTN-025), the follow-on trial to ASPIRE in which women were given the opportunity to use the ring for one year. The study was conducted in two parts. Phase I involved 187 former ASPIRE participants who had been assigned to use the dapivirine ring and who took part in either a focus group or in-depth interview. Phase 2 involved 58 former participants who opted to enroll in HOPE and 55 male partners. Results and more info…
MTN-030/IPM 041 – A Phase I trial of a vaginal ring containing the ARV drug dapivirine and the contraceptive hormone levonorgestrel that assessed the ring’s safety as well as absorption patterns of dapivirine and different dosages of levonorgestrel in vaginal tissue and in blood. MTN-030/IPM 041, which was conducted at two U.S. sites, found the ring was well-tolerated with no safety concerns. The study represented an important first step toward developing a product for women that could both protect against HIV and prevent unintended pregnancy. (See also MTN-044/IPM 053/CCN019 and MTN-038.) Results and more info…
MTN-029/IPM 039 – The first study of its kind involving the dapivirine vaginal ring in breastfeeding women, MTN-029/IPM 039 found that very low concentrations of dapivirine released from the ring into the vagina were absorbed by breastmilk in lactating women. Sixteen women who were no longer breastfeeding but were still producing breast milk were enrolled into the study and used the ring for 14 consecutive days. Results, which were reported at IAS 2017, supported additional studies of the dapivirine ring in breastfeeding women. (See MTN-043/B-PROTECTED.) Results and more info…
MTN-028 – A Phase I trial that evaluated two vaginal rings, each containing a different dose of the same two ARV drugs – a CCR5-receptor antagonist called vicriviroc (MK-4176) and an integrase inhibitor, MK-2048. MTN-028 sought to understand the optimal doses of MK-4176 and MK-2048 needed to achieve concentrations of drug in tissue that could feasibly provide HIV protection. According to results, reported in 2019, both doses of rings were safe and well tolerated. MK-4176 and MK-2048 were detectable in plasma and tissues in higher amounts in the higher dose ring compared to the lower dose ring. MTN-028 and MTN-027 were the first clinical studies of an integrase inhibitor as a potential microbicide.
MTN-027 – A Phase I study, which along with its companion study, MTN-028, was one of the first clinical trials to test a type of ARV called an integrase inhibitor as a potential microbicide. MTN-027 looked at the safety of three vaginal rings: one that contained the integrase inhibitor MK-2048; a second ring containing vicriviroc (MK-4176), which is a CCR5-receptor antagonist; and a third ring that contained both active drugs. Results, reported in 2019, found the rings to be safe and acceptable among the 48 women in the study from two U.S. sites.
MTN-026 – A Phase I study that evaluated the rectal safety of a gel containing 0.05 percent of the antiretroviral drug dapivirine, which was originally developed for vaginal use, as well as the levels of drug detected in blood, rectal fluid and rectal tissue after use. The study, which enrolled 27 HIV-negative cisgender and transgender men and women at sites in Thailand and the U.S., showed the gel was well-tolerated and acceptable to participants, with tissue concentrations suggesting a longer-acting formulation or a higher-dose gel would be required to provide effective protection from HIV transmission through anal sex. (See also MTN-033.) Results and more info…
MTN-025/HOPE (HIV Open Label Prevention Extension) – An open-label follow-on trial to ASPIRE (MTN-020) in which former ASPIRE participants were offered the opportunity to use the dapivirine ring (there was no placebo) in the context of a study designed to collect additional information about safety and how women would use the ring knowing that it had been shown to reduce the risk of HIV in ASPIRE. HOPE enrolled 1,456 women at 14 sites in Malawi, South Africa, Uganda and Zimbabwe. Women were free to accept the ring or not, and to change their minds at any time during the study. Results, which were presented at IAS 2019, found that ring was well-tolerated, consistent with the safety profile seen in ASPIRE, and the majority of women from ASPIRE chose the ring being offered. Measures of adherence also indicated they were willing to use the ring to protect themselves against HIV. Results and more info…
MTN-024/IPM 31 – A Phase I safety study of the monthly dapivirine ring in 96 post-menopausal women conducted at three sites in the U.S. Results, which were published in 2019, found the ring was safe and well-tolerated.
MTN-023/IPM 30 – A Phase I safety study of the dapivirine vaginal ring in adolescent girls that was conducted at six U.S. research sites from 2013 to 2016 in collaboration with the National Institutes of Health-funded Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions. The study enrolled 96 girls ages 15-17 at six U.S. sites who were randomly assigned to use either the dapivirine ring or a placebo ring each month for six months. Results, which were presented at IAS 2017, found no differences in safety outcomes between the dapivirine ring and the placebo ring. Ring acceptability and adherence to ring use were also high. Results and more info…
MTN-020/ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) – was a Phase III study to determine whether a vaginal ring containing the ARV drug dapivirine is a safe and effective method for protecting against the sexual transmission of HIV when used by women for a month at a time. ASPIRE enrolled 2,629 sexually active HIV-negative women ages 18-45 and was conducted between 2012-2015 at 15 clinical research sites in Malawi, South Africa, Uganda and Zimbabwe. Results, reported in 2016, found HIV risk was reduced by 27 percent overall and no safety concerns. HIV risk was cut by more than half (56 percent) in women older than 21, who also appeared to use the ring most consistently. Results of an exploratory analysis reported at AIDS 2016 found the level of HIV protection for those who used the ring most consistently was at least 56 percent and as high as 75 percent or more with near perfect use. Results and more info…
MTN-017 – A Phase II trial designed to evaluate the rectal safety, drug absorption and acceptability of a reduced glycerin formulation of tenofovir gel, as well as oral Truvada, at sites in Peru, South Africa, Thailand and the U.S., including Puerto Rico. The study enrolled 195 cisgender men and transgender women who have sex with men. Results, which were reported February 2016, found the gel was safe to use, with participants preferring to use the gel around the time of sex as opposed to daily, but that they were also more likely to use daily oral PrEP than a daily gel. Results and more info…
MTN-016/EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) – An observational study and data registry to understand the effects, if any, the use of ARV-based HIV prevention products may have on pregnancy and infant outcomes. The study enrolled women who unintentionally became pregnant while participating in the MTN-003/VOICE, MTN-020/ASPIRE or MTN-025/HOPE studies (and then immediately stopped use of the study product), as well as their babies. Women and their babies from MTN-002 and MTN-008 were also included. In total, MTN-016 has collected data on 460 women and 413 infants. Among the study’s findings, researchers report no significant differences in pregnancy and infant outcomes between women in the ASPIRE study who were using the dapivirine ring at the time they became pregnant and women from the placebo group who became pregnant, supporting additional safety studies of the dapivirine ring throughout pregnancy. (See also MTN-042/DELIVER.) Results and more info…
MTN-015 – A long-term, observational study that was designed to track the nature of HIV progression and treatment response among women who acquired HIV while taking part in an MTN “parent study” of an ARV-based HIV prevention product. In total, MTN-015 enrolled 479 women from one of four MTN studies (HPTN-035, MTN-003/VOICE, MTN-020/ASPIRE and MTN-025/HOPE), beginning in 2013. Results suggest there are no differences in the progression of HIV or in response to treatment (e.g., development of drug resistance) among women who received an ARV-based prevention product and those who received a placebo. Results and more info…
MTN-014 – A Phase I study that examined drug absorption patterns in both rectal and vaginal tissue when a reduced glycerin formulation of tenofovir gel was applied either vaginally or rectally. The study enrolled 14 women at a U.S.-based clinical research site. Results, reported in 2015, demonstrated that when tenofovir gel was applied into the vagina, a low amount of active drug was distributed to the rectum and, similarly, when the gel was applied into the rectum, a low amount of active drug was distributed to the vagina. Results and more info…
MTN-013/IPM 026 – A Phase I safety and drug absorption study that tested 28-day use of vaginal rings containing either dapivirine, maraviroc, or the two ARVs combined, and was conducted among 48 women at three U.S. sites. The study was the first clinical trial of a vaginal ring containing maraviroc, and the first to test a vaginal ring with two active drugs. Results, reported in 2014, found the ring was safe in women and evidence of dapivirine in cervical tissue and blood. In addition, laboratory tests of tissues samples showed that dapivirine was able to block HIV infection, though levels of maraviroc were not sufficient to have a similar effect. Results and more info…
MTN-012/IPM 010 – A Phase I study that assessed the safety and tolerance of a vaginal microbicide containing the ARV drug dapivirine when applied topically to the penis of sexually abstinent men. Results, which were reported in 2012, found the gel safe and well-tolerated.
MTN-011 – A Phase I study that aimed to determine the effect vaginal sex may have on drug absorption and activity of tenofovir gel. The study, which was conducted at two sites in the U.S., enrolled 24 couples. Study results, presented in 2014, showed that drug levels were highest when tenofovir gel was used one hour before and one hour after sex, suggesting that the timing of gel use relative to sex impacts the drug’s absorption and activity.
MTN-009 – Also called the HIV Drug Resistance Study, MTN-009 assessed the prevalence of HIV drug resistance in KwaZulu-Natal, South Africa. Results, published in 2013, found the prevalence of HIV drug resistance was 7.4 percent, with the majority of women with resistance having virus with the K103N mutation that confers resistance to most drugs in the class of ARVs called non-nucleoside reverse transcriptase inhibitors. Results and more info…
MTN-008 – An expanded Phase I safety and drug absorption study of tenofovir gel used daily for seven consecutive days in women in their third trimester of pregnancy, and women who were breastfeeding. The study enrolled 90 pregnant women – 45 women at 37 weeks gestation and 45 women at 34 weeks gestation; and 16 women who were breastfeeding. MTN-008 was a follow-up study to MTN-002 and was conducted at two U.S. sites. Results, first presented in 2013, indicated daily use of tenofovir gel in the third trimester of pregnancy was safe and well-tolerated, tenofovir did not accumulate in breast milk, and absorption of the drug in breastfeeding infants was low. (See also MTN-002.) Results and more info…
MTN-007 – A Phase I follow-up study to RMP-02/MTN-006 that found rectal use of a reduced glycerin formulation of tenofovir gel safe and acceptable among the 60 men and women who took part in the study at three U.S. sites. Based on results, which were first reported in 2012, researchers proceeded with a Phase II trial of reduced glycerin tenofovir gel, MTN-017. (See also MTN-006 and MTN-017.) Results and more info…
MTN-006 (RMP-02/MTN-006) – A Phase I study involving 18 HIV-negative men and women designed to determine whether the vaginal formulation of tenofovir gel is safe to use in the rectum, and through novel laboratory studies, if the gel prevents HIV infection in rectal tissue sampled from study participants. Results, reported in 2011, found HIV infection was significantly inhibited in rectal tissue sampled from participants who used tenofovir gel daily for one week. Because some participants experienced gastrointestinal side effects, researchers subsequently reformulated the gel to include less glycerin. The study was conducted in collaboration with the Division of AIDS Integrated Pre-Clinical/Clinical Program for HIV Topical Microbicides of the National Institute of Allergy and Infectious Diseases. (See also MTN-007 and MTN-017.) Results and more info…
MTN-005 – An expanded safety and acceptability study of a non-medicated vaginal ring made of a silicone elastomer that enrolled 195 sexually active, HIV-negative women. The study was conducted at three sites – one in India and two in the United States.
MTN-004 – A Phase I study that tested the safety and acceptability of VivaGel® (SPL7013 Gel) in HIV-negative women ages 18 to 24. The study, a collaboration with the NIH’s Adolescent Trials Network (ATN) for HIV/AIDS Interventions, was conducted at two U.S. sites and one in Puerto Rico. Results, reported in May 2010, found VivaGel generally well-tolerated but less acceptable to use than the two placebo gels studied. Results and more info…
MTN-003/VOICE (Vaginal and Oral Interventions to Control the Epidemic) – A Phase IIb study that tested the safety and effectiveness of two different HIV prevention approaches among 5,029 women in South Africa, Uganda and Zimbabwe: daily use of an ARV tablet (tenofovir or Truvada) or daily use of a vaginal gel (tenofovir gel). The study was conducted from 2009 to 2012. Results, first reported in 2013, found all three products were safe but none was effective; most participants did not use them daily as recommended. Young, unmarried women were least likely to use study products and the most likely to acquire HIV. Results and more info…
MTN-003B/VOICE B – Also known as the Bone Mineral Density Sub-study, VOICE B was an observational study in a subset of participants in VOICE designed to explore the potential effects, if any, that daily use of oral ARVs may have on bone health in HIV-negative women, and in particular, pre-menopausal women in Africa. VOICE B involved 518 women from Uganda and Zimbabwe who were assigned to one of the oral tablet regimens (oral tenofovir, oral Truvada or oral placebo) in VOICE. VOICE B found small decreases in bone mineral density among young women with higher adherence to the oral tablet tenofovir, findings that are consistent with previous studies, which resolved after stopping its use. Results and more info…
MTN-003C/VOICE C – Also known as the Community and Adherence Sub-study, VOICE C was designed to identify community-based factors and beliefs that may have influenced women’s ability and willingness to use the products being tested in VOICE and was conducted in parallel with VOICE at a single site. Participants included 102 women enrolled in VOICE, as well as male partners, members of the site’s Community Advisory Board (CAB) and community stakeholders. Results suggest women didn’t use the products because of worries about side effects and the stigma associated with ARVs, which are used for treating people with HIV; and not knowing if they’d been assigned to use an active product or placebo. Results and more info…
MTN-003D/VOICE D – A behavioral sub-study of VOICE that aimed to understand women’s actual and reported use of study products and sexual behavior during their participation in VOICE. Stage 1 involved 88 women who took part in individual in-depth interviews after exiting VOICE and before the trial’s results were publicly reported. Stage 2 was implemented in response to VOICE results and involved 127 former participants who took part in in-depth interviews and/or focus group discussions after learning the results of blood tests indicating their actual patterns of product use during the trial. The most common themes that emerged were fears about the products and their side effects, which were primarily fueled by other participants, relatives and community members’ negative attitudes about the products. Results and more info…
MTN-002 – The first study of a candidate topical microbicide to be conducted in pregnant women, and importantly, served as both a platform and blueprint for ensuing studies of microbicide safety in pregnancy. MTN-002 sought to understand whether tenofovir gel, which was being evaluated in trials to support its potential licensure, would be safe to use during pregnancy. The Phase I study involved giving a single dose of tenofovir gel to 16 healthy, HIV-negative women hours before they gave birth by scheduled Cesarean section. Results, reported in 2010, found only small amounts of drug were absorbed into the mother’s bloodstream, amniotic fluid and umbilical cord (fetal) blood; and no serious side effects in either the mothers or their newborns. (See also MTN-008.) Results and more info…
MTN-001 – A Phase II trial that looked at how tenofovir is absorbed in the body as either an oral tablet or a vaginal gel, as well as women’s preferences for and ability to adhere to the daily regimens of each approach. The study involved 144 women in South Africa, Uganda and the U.S., who used each product daily for six weeks, as well as the two together. The results of drug absorption studies, published in 2013, found the gel was associated with vaginal tissue drug levels more than 130-times higher than the oral tablet; the tablet was associated with a 56-times higher concentration of active drug in blood compared to the gel. Although self-reported adherence was very high (94 percent) and most women said they liked both products, drug serum concentrations indicated only 64 percent of the women took the tablets consistently. Results and more info…
See also information on these completed trials:
HPTN 035 - A multi-center clinical trial that evaluated the safety and effectiveness of two different candidate microbicides, BufferGel® and PRO 2000, in 3,100 sexually active HIV-negative women at seven sites in Africa and the U.S. Results and more info…
HPTN 059 - A trial that assessed the safety and acceptability of tenofovir gel used either daily or before each act of sex in 200 HIV-negative women at three sites in India and the U.S. Results and more info…