Drug Database: Dapivirine

What is dapivirine?What is dapivirine?

What is dapivirine?

Dapivirine is an investigational drug that is being studied as a topical microbicide to prevent sexual transmission of HIV.⁶

Dapivirine belongs to a class of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).⁷ NNRTIs attach to and block an HIV enzyme called reverse transcriptase.

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do topical microbicides work?How do topical microbicides work?

How do topical microbicides work?

Topical microbicides come in many different forms, including gels, creams, films, and vaginal rings (also called intravaginal rings or IVRs). These products are designed to prevent HIV infection during sex, so they are used close to where HIV might enter the body during sexual activities—either the vagina or rectum.^7,8

Researchers have studied several different types of dapivirine-based microbicide products, including gels, vaginal rings, and a vaginal film.^9-14 The monthly dapivirine ring is furthest along in development and has completed Phase 3b clinical trials.^3,4 Regulatory approval of the monthly dapivirine ring has been received in certain countries in Eastern and Southern Africa.²

Select clinical trials of dapivirineSelect clinical trials of dapivirine

Select clinical trials of dapivirine

Dapivirine-Based Vaginal Ring

Study Names: (1) Ring Study; IPM 027; NCT01539226 and (2) DREAM Study; IPM 032; NCT02862171

Phase: The Ring study was a Phase 3 trial, and the DREAM study was a follow-up Phase 3b trial.
Status: The Ring and DREAM studies have both been completed.
Locations: South Africa and Uganda
Purpose: The purpose of the Ring study was to evaluate whether a monthly dapivirine vaginal ring was safe and effective in protecting women against sexually acquired HIV. The DREAM study continued to evaluate the safety of the dapivirine vaginal ring and also looked at participant adherence to the vaginal ring.^3,9
Selected Study Results: Results from the Ring study published in The New England Journal of Medicine (2016) showed that the monthly dapivirine ring was safe and effective. The risk of HIV infection in women was reduced by 31% as compared to placebo. Results from the follow-on DREAM study published in Lancet HIV (2021) revealed no new safety concerns with the dapivirine ring. Participant adherence to monthly ring use was improved in the DREAM study compared to the Ring study.^15,16

Study Names: (1) ASPIRE Study; MTN-020; NCT01617096 and (2) HOPE Study; MTN-025; NCT02858037

Phase: The ASPIRE study was a Phase 3 trial, and the HOPE study was a Phase 3b follow-up trial.
Status: The ASPIRE and HOPE studies have both been completed.
Locations: Malawi, South Africa, Uganda, and Zimbabwe
Purpose: The purpose of the ASPIRE study was to evaluate whether a dapivirine vaginal ring was safe and effective in protecting women against sexually acquired HIV. The HOPE study continued to evaluate the safety of the dapivirine vaginal ring and also looked at participant adherence to the vaginal ring.^4,17
Selected Study Results: Results from the ASPIRE study published in The New England Journal of Medicine (2016) demonstrated that the monthly dapivirine ring was safe and reduced the risk of HIV infection in women by 27% as compared to placebo. Findings from the follow-on HOPE study presented in Lancet HIV (2021) continued to show that the dapivirine ring was well tolerated with a safety profile similar to what was previously seen in other Phase 3 dapivirine ring trials. Adherence to the monthly dapivirine ring among HOPE study participants was good and improved over what was seen among ASPIRE study participants.^18,19

Study Names: DELIVER Study; MTN-042; NCT03965923

Phase: 3b
Status: This study is ongoing, but not recruiting participants
Locations: Malawi, South Africa, Uganda, and Zimbabwe
Purpose: The purpose of this trial is to evaluate the maternal and infant safety of the monthly dapivirine ring and daily oral Truvada in pregnant women and their infants.^20,21
Selected Study Results: Results presented at CROI 2023 and CROI 2024 showed that negative pregnancy outcomes and complications were uncommon in women who used either the monthly dapivirine ring or daily oral Truvada during the second and third trimesters of pregnancy. Negative pregnancy outcome and complication rates were found to be similar to those seen in local communities where the study was being conducted.^21,22

Study Names: B-PROTECTED Study; MTN-043; NCT04140266

Phase: 3b
Status: This study has been completed.
Locations: Malawi, South Africa, Uganda, Zimbabwe
Purpose: The purpose of this trial was to evaluate monthly dapivirine ring and daily oral Truvada safety and drug detection in breastfeeding mother-infant pairs.^23,24 
Selected Study Results: Results presented at CROI 2023 indicate that use of the monthly dapivirine ring in breastfeeding women appears to be safe. Although dapivirine could be detected in breastmilk, dapivirine concentrations in infant plasma were low. In the Truvada arm, drug concentrations in breastfeeding infants of women using daily oral Truvada were also low. There were no serious or severe drug-related side effects in mothers. All side effects in infants were unrelated to study products.²⁴

For more details on the studies listed above, see the Health Professional version of this drug summary.

Additional dapivirine-based vaginal ring studies have also been completed or are ongoing or planned. These include the following trials:

• MTN-036/IPM 047 (NCT03234400) and IPM 054 (NCT05416021): A Phase 1 pharmacokinetic and safety study and a Phase 1 bioavailability study evaluating extended duration (3-month) dapivirine rings. MTN-036/IPM 047 has been completed and results are available from J Int AIDS Soc (2021). IPM 054 is ongoing, but not recruiting participants.^10,25
• MTN-044/IPM 053/CCN019 (NCT03467347) and IPM 056/CCN019B (NCT05041699): Phase 1 and 1b pharmacokinetic and safety studies assessing multipurpose prevention technology (MPT) IVRs containing dapivirine and levonorgestrel. MTN-044/IPM 053/CCN019 has been completed and results were presented at HIVR4P 2021. IPM 056/CCN019B is currently recruiting participants.^11,26
• REACH; MTN-034 (NCT03593655): A completed Phase 2a study that evaluated the safety of and adherence to the monthly dapivirine vaginal ring and oral Truvada in adolescent and young adult female participants.^27,28 Results were presented at IAS 2021 and CROI 2022.

Other Dapivirine-Based Microbicide Formulations

Other dapivirine-based microbicide formulations have been studied in clinical trials. These include Phase 1 trials of a vaginal film (NCT01924091 and NCT01548560), a Phase 1 trial of a rectal gel (NCT03393468), and Phase 1/2 trials of vaginal gels (NCT00799058 and NCT00917891). A combination vaginal gel that contains dapivirine and darunavir has also been studied in a Phase 1 trial (ISRCTN23353517).^12-14,29-31

What side effects might dapivirine cause?What side effects might dapivirine cause?

What side effects might dapivirine cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of dapivirine listed above.

Ring Study (NCT01539226); DREAM Study (NCT02862171)

In the Ring study, the dapivirine ring was reported to be safe, with no difference in safety concerns between the dapivirine ring group and the placebo group. Some of the side effects related to the dapivirine ring included abnormal uterine bleeding, pelvic discomfort or pain, and lower abdominal (suprapubic) pain. All of these side effects were mild in severity.¹⁵

Results from the follow-on DREAM study showed a comparable safety profile to what was seen in the Ring Study. Among 941 participants who enrolled in the DREAM study, approximately 66% experienced a side effect. Only six participants experienced a side effect that was considered to be related to the study product. There were no treatment-related serious side effects.¹⁶

ASPIRE Study (NCT01617096); HOPE Study (NCT02858037)

In the ASPIRE study, the use of the dapivirine ring was reported to be safe. Similar to the Ring study, there was no difference in the occurrence of side effects between the dapivirine ring group and the placebo group. In the study, side effects related to the dapivirine ring included inflammation, reddening, or swelling of the cervix; urinary tract infection; loss of bladder control; headache; pain during sex; and pelvic pain.¹⁸

The follow-on HOPE study demonstrated a safety profile similar to what has been seen in other Phase 3 dapivirine trials. Among 1,456 participants who enrolled in the study, no serious or severe side effects related to dapivirine occurred. Moderate side effects related to dapivirine occurred in just two participants.¹⁹

DELIVER Study (NCT03965923)

Results from the DELIVER study showed that negative pregnancy outcomes and complications were uncommon in women who used either the monthly dapivirine ring or daily oral Truvada during the second and third trimesters of pregnancy. Negative pregnancy outcome and complication rates were found to be similar to those seen in local communities where the study was being conducted. The most common pregnancy complications reported in both groups were disorders associated with hypertension.^20-22

B-PROTECTED Study (NCT04140266)

In the B-PROTECTED study evaluating monthly dapivirine ring and daily oral Truvada use in breastfeeding mother-infant pairs, most side effects were mild or moderate in severity. Among mothers, there were no serious or severe side effects related to the study product. Among infants, all of the side effects that occurred were unrelated to the study product.^23,24

Because dapivirine-based vaginal rings are still being studied, information on possible side effects of the drug products is not complete. As testing of dapivirine-based vaginal rings continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying dapivirine?Where can I get more information about clinical trials studying dapivirine?

Where can I get more information about clinical trials studying dapivirine?

More information about dapivirine-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem compound summary for CID 214347, dapivirine. Accessed March 26, 2024
2. Population Council: press release, dated October 4, 2022. Population Council completes asset purchase agreement from the International Partnership for Microbicides. Accessed March 26, 2024
3. International Partnership for Microbicides, Inc. A follow-on, open-label trial to assess continued safety of and adherence to the dapivirine (25 mg) vaginal Ring-004 in healthy, HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 25, 2016. NLM Identifier: NCT02862171. Accessed March 26, 2024
4. International Partnership for Microbicides, Inc. A Phase 3B open-label follow-on trial to assess the continued safety of and adherence to a vaginal ring containing dapivirine in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 18, 2016. NLM Identifier: NCT02858037. Accessed March 26, 2024
5. International Partnership for Microbicides (IPM): press release, dated December 9, 2021. IPM statement on US Food and Drug Administration review of dapivirine vaginal ring. Accessed March 26, 2024
6. Jefferys R. The PrEP and microbicides pipeline 2022. Treatment Action Group Pipeline Report 2022. Accessed March 26, 2024
7. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385. Accessed March 26, 2024
8. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. Accessed March 26, 2024
9. International Partnership for Microbicides, Inc. A multi-centre, randomised, double-blind, placebo-controlled safety and efficacy trial of a dapivirine vaginal matrix ring in healthy HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 21, 2012. NLM Identifier: NCT01539226. Accessed March 26, 2024
10. International Partnership for Microbicides, Inc. A Phase 1, randomized pharmacokinetics and safety study of extended duration dapivirine vaginal rings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 25, 2017. NLM Identifier: NCT03234400. Accessed March 26, 2024
11. International Partnership for Microbicides, Inc. A randomized, Phase 1, open-label study in healthy HIV-negative women to evaluate the pharmacokinetics, safety and bleeding patterns associated with 90-day use of matrix vaginal rings containing 200 mg dapivirine and 320 mg levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 9, 2018. NLM Identifier: NCT03467347. Accessed March 26, 2024
12. International Partnership for Microbicides, Inc. Comparison of the pharmacokinetics and pharmacodynamics of single dose dapivirine vaginal gel and film formulation. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 13, 2013. NLM Identifier: NCT01924091. Accessed March 26, 2024
13. National Institute of Allergy and Infectious Diseases (NIAID). An open label randomized Phase 1 pharmacokinetic study of dapivirine gel administered rectally to HIV-1 seronegative adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 2, 2018. NLM Identifier: NCT03393468. Accessed March 26, 2024
14. International Partnership for Microbicides, Inc. A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine gel 4759, 0.05% 2.5g and dapivirine gel 4789, 0.05% 2.5g formulations as compared to the vaginal HEC-based universal placebo gel, 2.5g in healthy HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 26, 2008. NLM Identifier: NCT00799058. Accessed March 26, 2024
15. Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016;375(22):2133-2143. doi:10.1056/NEJMoa1602046. Accessed March 26, 2024
16. Nel A, Niekerk N van, Baelen BV, 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-e86. doi:10.1016/S2352-3018(20)30300-3. Accessed March 26, 2024
17. International Partnership for Microbicides, Inc. A multi-center, randomized, double-blind, placebo-controlled Phase 3 safety and effectiveness trial of a vaginal matrix ring containing dapivirine for the prevention of HIV-1 infection in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 8, 2012. NLM Identifier: NCT01617096. Accessed March 26, 2024
18. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375(22):2121-2132. doi:10.1056/NEJMoa1506110. Accessed July 11, 2023
19. Baeten JM, Palanee-Phillips T, Mgodi NM, et al. Uptake and use of a vaginal ring containing dapivirine for HIV-1 prevention in African women: an open-label extension study. Lancet HIV. 2021;8(2):e87-e95. doi:10.1016/S2352-3018(20)30304-0. Accessed March 26, 2024
20. National Institute of Allergy and Infectious Diseases (NIAID). Phase 3b, randomized, open label safety trial of dapivirine vaginal ring and oral Truvada® use in pregnancy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 24, 2019. NLM Identifier: NCT03965923. Accessed March 26, 2024
21. Bunge KE, Balkus J, Mhlanga F, et al. DELIVER: a safety study of a dapivirine vaginal ring and oral PrEP during pregnancy. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Accessed March 26, 2024
22. Mhlanga F, Bunge KE, Fairlie L, et al. Safety of dapivirine vaginal ring and oral PrEP for HIV prevention in the second trimester. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Abstract 168. Accessed March 26, 2024. Accessed March 26, 2024
23. National Institute of Allergy and Infectious Diseases (NIAID). Phase 3B, randomized, open-label, safety, and drug detection study of dapivirine vaginal ring and oral Truvada® in breastfeeding mother-infant pairs. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2019. NLM Identifier: NCT04140266. Accessed March 26, 2024
24. Owor M, Noguchi L, Horne E, et al. Dapivirine vaginal ring safety and drug detection in breastfeeding mother-infant pairs. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Accessed March 26, 2024
25. International Partnership for Microbicides, Inc. A Phase I, open-label, randomized, crossover trial to investigate the relative bioavailability of the 25 mg dapivirine vaginal Ring-004 inserted every 30 days and 100 mg DPV Ring-008 inserted for 90 days in healthy female participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 14, 2022. NLM Identifier: NCT05416021. Accessed March 26, 2024
26. International Partnership for Microbicides, Inc. A randomized, double-blind, Phase 1b study in healthy HIV-negative women to evaluate the pharmacokinetics, safety, and bleeding patterns associated with 90-day use of core-sheath vaginal rings releasing dapivirine and levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 24, 2021. NLM Identifier: NCT05041699. Accessed March 26, 2024
27. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2a crossover trial evaluating the safety of and adherence to a vaginal matrix ring containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate in an adolescent and young adult female population. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 10, 2018. NLM Identifier: NCT03593655. Accessed March 26, 2024
28. Microbicide Trials Network (MTN) website. About the REACH Study (MTN-034). Accessed March 26, 2024
29. International Partnership for Microbicides, Inc. Assessing the Safety of Dapivirine Gel and Film Formulations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01548560. Accessed March 26, 2024
30. International Partnership for Microbicides, Inc. A double-blind, randomized, placebo-controlled Phase I/II study to evaluate the safety and acceptability of dapivirine gel 4759, 0.05%, 2.5g, a vaginal microbicide, conducted using daily monitored adherence in healthy, HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 8, 2009. NLM Identifier: NCT00917891. Accessed March 26, 2024
31. ISRCTN Registry. ISRCTN number: ISRCTN23353517; Assessing the safety, pharmacokinetics and pharmacodynamics of single and 14 days dosing with two vaginal microbicide formulations containing either darunavir, or dapivirine and darunavir. Accessed March 26, 2024