An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques

Derby, N., Aravantinou, M., Kenney, J. et al.

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy. Vaginal fluid from treated macaques has in vitro activity against HIV, HSV-2, and HPV. Herein, we assessed the ability of the MZCL IVR to protect macaques against repeated co-challenge with HSV-2 and SHIV-RT (simian immunodeficiency virus [SIV] containing the reverse transcriptase gene from HIV) and prevent hormonal cycling. We evaluated in vivo drug release in co-challenged macaques by measuring drug levels in blood and vaginal fluid and residual drug levels in used IVRs. The MZCL IVR significantly prevented SHIV-RT infection, reduced HSV-2 vaginal shedding, and prevented cycling. No non-nucleoside HIV reverse transcriptase inhibitor (NNRTI)-resistant SHIV was detected in macaques that became infected after continuous exposure to MZC from the IVR. Macaques wearing the MZCL IVR also had carrageenan levels in vaginal fluid expected to protect from HPV (extrapolated from mice) and LNG levels in blood associated with contraceptive efficacy. The MZCL IVR is a promising MPT candidate that warrants further development.

June 19, 2017
Year of publication
Resource types
Journal and research articles
multipurpose prevention technologies, HIV prevention, co-infections, sexually transmitted infections (STIs), unintended pregnancies, human papillomavirus (HPV), herpes simplex virus-2 (HSV-2), intravaginal ring

Similar Resources

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs).

To understand the uptake of HIV services by adolescent women, the authors conducted a retrospective analysis of patient-level data (2011–2013) on services for antenatal care (ANC) and prevention of mother-to-child transmission (PMTCT) in 36 facilities in 5 districts in Zimbabwe.

Remarkable progress is being made on HIV treatment. Ahead of World AIDS Day, UNAIDS has launched a new report showing that access to treatment has risen significantly. In 2000, just 685 000 people living with HIV had access to antiretroviral therapy.

This study aimed to evaluate the impact of clinic-based prevention of mother-to-child transmission (PMTCT) community support by trained lay health workers in addition to standard clinical care on PMTCT infant outcomes.

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women.

Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence.

For persons at risk of HIV infection who practice receptive anal intercourse (RAI), topical rectal microbicides represent a promising option for coitally-dependent protection.

Many countries are working to reduce or eliminate mother-to-child transmission (MTCT) of HIV. Prevention efforts have been conceptualized as steps in a cascade but cascade completion rates during and after pregnancy are low.

This paper documents the development of the global and national monitoring and reporting systems for PMTCT and paediatric HIV care and treatment programmes, achievements and remaining challenges.

The heightened risk of HIV infection among female sex workers (FSWs) has been clearly established across settings. In sub-Saharan Africa (SSA), FSWs have an estimated HIV prevalence of 36.9% as compared to 7.4% in the general adult female population. In the Iringa region of Tanzania, a…