HIV Prevention

Exploring size, colour and fragrance preferences for vaginal rings

Drug-releasing vaginal rings are currently available for contraception and hormone replacement therapy. The European Medicines Agency (EMA) announced in July 2020 a “positive benefit-risk opinion” on the use of the vaginal ring containing the anti-HIV medication dapivirine. A critical – but neglected – aspect of ring development is assessment of user preferences for product attributes that increase acceptance of the product, and in turn increase adherence and efficacy. In this project, placebo rings having different sizes, colours and fragrances will be developed, and women’s preferences will be assessed.

This study aims to explore women’s preferences and attitudes to different vaginal ring product attributes.  We will conduct three focus group discussions (FGDs)  in eThekwini, with up to 10 women, aged 18–35, per group. Vaginal rings developed in different sizes, colours and fragrances will be shown to women and their opinions on the product attributes and preferences will be discussed. This study will commence in first quarter of 2021.

Funder/Sponsors:           University of the Witwatersrand, Queens University Belfast

Principal Investigator     Mags Beksinska (MRU), Karl Malcolm (QUB)

Site:       MRU, Durban

Pretreatment HIV drug resistance
This study looks at the prevalence and patterns of HIV resistance in women who seroconverted during the ECHO trial by testing stored blood samples. Blood samples were collected for storage in women who tested positive for HIV during the ECHO trial. We are testing samples from 8 of the South African study sites. Testing has commenced and is currently ongoing.

Funder/Sponsors:           GEMS, University of Pittsburgh

Principal Investigator     Dr Ivana Beesham (MRU), Dr Urvi M Parikh (GEMS), Dr John W Mellors (GEMS), Dr Jared Baeten (UW), Dr Carole Wallis (BARC)

Site:       MRU, Durban

Prospective Evaluation of Postpartum Engagement in HIV Care
The PEPEHC study aims to estimate the rate of attrition from HIV care and to identify factors associated with attrition form and retention in HIV care during postpartum period.  This study will enrol 500 pregnant women, living with HIV and diagnosed during the current pregnancy.  Participant will be followed up over a period of two years. Field work  commenced in February 2018 and enrolment will be completed in 2020.

 

 

Funder/Sponsor: NIH – National Institute of Health (R01: MH112385-01)
Principal Investigators: Prof Jenni Smit
Site: PMMH Gateway Clinic
Collaborators Massachusetts General Hospital MGH and Harvard Medical School

 

Safer Conception for Women Study – Understanding use of Periconception PrEP: The ZINK Study “Protect yourself before pregnancy”

Pre-exposure prophylaxis (PreP) use of oral tenofovir/emtricitabine (TDF/FTC) have been shown to offer protection against HIV acquisition in sero-discordant couples. PreP may offer HIV-negative women in endemic settings with an effective risk reduction strategy that will allow them to safely conceive if they are in sero-discordant relationships. Evaluating uptake of and adherence to antiretrovirals as pre-exposure prophylaxis in this population is crucial to understanding whether and how this novel prevention strategy should be incorporated into HIV-risk reduction packages for at- risk women planning or with pregnancy.

The PreP Safer Conception for Women study is a single-arm longitudinal study that will offer daily oral tenforvir/emtricitabine (TDF/FTC) as a pre-exposure prophylaxis for periconception. We enrolled 330 HIV-uninfected women in KwaZulu Natal, South Africa, who reported personal or partner plans for pregnancy with an infected or unknown serostatus partner. PrEP is offered as part of a safer conception package inclusive of couples-based HIV counselling and testing (CHCT), antiretroviral therapy (ART) for the infected partner, treatment for STIs and safer conception strategies, such as, limiting sex without condoms to peak fertility. Women have the option to take PrEP during pregnancy.

This clinical trial commenced in 2017 and completed recruitment in January 2020. The study team is currently conducting follow-up visits, telephonically and in person. In-depth interviews are also underway. The DSMB for this clinical trial have found it to be safe and important to continue until study completion. This clinical trial was audited by SAHPRA in 2019 and found to adhere to satisfactory ethical standards for conducting a clinical trial in South Africa.

 

A sub-study investigating sexually transmitted infections commenced in December 2019. Participants from the main PrEP Safer Conception for Women study were invited to participate, of which 51 participants enrolled.  The sub-study present participants with the opportunity to be tested and treated for active STI infections.

 

Funder/Sponsor: NIH/ Lynn Matthews, The University of Alabama at Birmingham, Department of Medicine.
Principal Investigators: Jenni Smit, (MRU) Lynn Matthews ( University of Alabama)
Site: MRU, Durban

HIV Prevention Completed Studies

Siyaphanta, Siyavimba!
ARV-Based Prevention and Treatment in High-Risk Women in Durban, South Africa

MatCH Research Unit and the HIV Center for Clinical and Behavioral Studies at Columbia University are conducting a study to explore female sex workers’ (FSW) knowledge, attitudes, and experiences with pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP), and other prevention options. No one strategy will likely be effective in eradicating HIV among FSW; rather a combination of context-specific targeted strategies, including ARV-based prevention/treatment and condoms, will be needed to reduce HIV incidence. However, combination prevention models for FSW have not been sufficiently developed and tested. This formative, qualitative research study on ARV-based HIV prevention and treatment for FSW will identify the structural, health system, interpersonal and individual-level barriers and facilitators that influence access to, use of, and adherence to ARV-based prevention and treatment among FSWs.

Funder/Sponsor: U.S. National Institute of Mental Health (R21MH113436).
Principal Investigators/: For further information about this study, please contact Professor Jennifer Smit, MatCH Research Unit at jsmit@mru.co.za or Professor Joanne Mantell, HIV Center for Clinical and Behavioural Studies, Columbia University at jem57@cumc.columbia.edu
Site: MatCH Research Unit Commercial City, Durban
PrEP study

 This ancillary study was conducted among women who initiated PrEP on-site during the ECHO Trial at the MRU, Commercial City site in Durban, South Africa. A questionnaire was administered that explored reasons for initiating and discontinuing PrEP, side effects experienced, perceived HIV risk, disclosure of PrEP use and reported adherence to PrEP.  In addition, women were contacted 4-6 months after exiting the study to explore post-trial access to PrEP.  The study found that PrEP uptake was high (43%), and women who initiated PrEP felt at risk of acquiring HIV. Most women had heard of PrEP for the first time by trial staff (91%) and three-quarters who initiated PrEP on-site continued at trial-exit. PrEP use declined post-trial exit with more than 50% of women discontinuing PrEP, and barriers relating to access emerged.

Manuscript link: Beesham, I., Heffron, R., Evans, S. et al. Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial. AIDS Behav (2020). https://doi.org/10.1007/s10461-020-03072-0

IPM 037B:-A qualitative research study to investigate non-adherence to the use of a vaginal ring as a possible preventative mechanism against HIV-1 uninfected women in the Clermont, KwaDabeka area of KwaZulu-Natal

IPM 037B is a multi-faceted qualitative research study to investigate non-adherence to the use of a vaginal ring as a possible preventative mechanism against HIV-1 among uninfected women in the Clermont/KwaDabeka area of KwaZulu-Natal. This study includes in depth semi-structured interviews (IDIs) with Ring Study participants, trial site staff and possibly male partners of the participants. Focus Group Discussions (FGDs) are also being conducted with community stakeholders, community males, female Ring Study participants, and the Community Advisory Group. Data collection is in progress.

Funder/Sponsor: International Partnership for Microbicides (IPM)
Principal Investigators/: J Smit (MatCH Research Unit)
Site: MatCH Research main office
The Quatro Study: Acceptability study of (placebo) vaginal delivery forms for preventing HIV and unintended pregnancy among young women in Zimbabwe and South Africa
Despite the crucial need, available products to prevent HIV infection and pregnancy, such as male condoms, female condoms, and microbicides, are not under women’s control and are inconsistently used, especially in low resource settings. The purpose of the Quatro study  was  to assess the acceptability, preferences, user experience and effect on sexual behavior of four different vaginal microbicide or MPT delivery forms, using placebo products in 18-30 year old  women: rapidly disintegrating vaginal insert, intravaginal ring (IVR), film and gel. The study also examines adherence to the dosage forms through objective markers, developed for each dosage form prior to the commencement of the study.

In addition, data collection activities were designed to inform development of product educational messages tailored for young women in these Sub-Saharan African settings. The study was  conducted in Durban, South Africa and Harare, Zimbabwe. The study  has been disseminated and  several key publications are available:

Montgomery, E.T., Beksinska, M., Mgodi, N., Schwartz, J., Weinrib, R., Browne, E.N., Mphili, N., Musara, P., Jaggernath, M., Ju, S., Smit, J.,  Chirenje, M.Z., Doncel, G.F., van der Straten, A. (2019). End-user preference for and choice of four vaginally-delivered HIV prevention methods among young women in Southern Africa: The Quatro Study. Journal of the International AIDS Society (JIAS).
ID:  JIAS-2018-08-0425 https://www.ncbi.nlm.nih.gov/pubmed/31069957

Browne, E.N., Montgomery, E.T., Mansfield, C., Boeri, M., Mange, B., Beksinska, M., Schwartz, J.L., Clark, M.R., Doncel, G.F., Smit, J., Chirenje, Z.M., van der Straten, A. (2019). Efficacy is Not Everything: Eliciting Women’s Preferences for a Vaginal HIV Prevention Product Using a Discrete-Choice Experiment. AIDS and Behaviour. Nov 6, doi: 10.1007/s10461-019-02715-1.

Weinrib, R., Browne, E.N., Shapley‑Quinn, M.K., van der Straten, A., Beksinska, M., Mgodi, N., Musara, P., Mphili, N., Schwartz, J.L, Ju, S., Hanif, H., Montgomery, E.T. (2019). Perspectives from Young South African and Zimbabwean Women on Attributes of Four (Placebo) Vaginal Microbicide Delivery Forms. AIDS and Behaviour.

https://link.springer.com/epdf/10.1007/s10461-019-025768?author_access_token=oAd5fGBOVWcBrP2qvsMSG_e4RwlQNchNByi7wbcMAY6f_jUt1E8UFR4xF-jEFFPBwR0Wsv0-9Laztk7EAK7cfrxKmPUJpW0JVa7zewQ791vAlxs13B6M7Me85U1NpZVQIeGDguv8Z-GBmu9B6qjOlw%3D%3D

Funder/Sponsor: United States Agency for International Development and The Bill & Melinda Gates Foundation via

CONRAD, Arlington, VA, United States and Women’s Global Health Imperative, RTI International, San Francisco, CA, United States

Investigators: WGHI, RTI International

Ariane van der Straten, Elizabeth Montgomery

Principal investigator

CONRAD

Jill Schwartz

MatCH Research Unit

Jenni Smit, Mags Beksinska

UZ-UCSF

Z Mike Chirenje, Nyaradzo Mgodi

Site: MRU Commercial City Clinic Site

Quatro

IPM Socio Behavioural Study

In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted with female participants and IDIs with male partners of the participants in the IPM 027 Ring Study at sites across South Africa. These interviews and discussions explored issues of adherence and acceptability of the vaginal ring.  The MatCH Research Socio-Behavioural Team conducted the analysis of these IDIs and FGDs.

Funder/Sponsor: International Partnership for Microbicides (IPM)
Principal Investigator: Prof J Smit (MatCH Research Unit)
Site: MatCH Research main office
IPM 027:- A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women
IPM 027 was a multi-centred, randomised, double-blind, placebo-controlled Phase II and Phase III trial to evaluate the long-term safety of Dapivirine in a silicone elastomer vaginal matrix ring, inserted once every 4 weeks for 2 years; in healthy, sexually active HIV-negative women, when compared to a placebo vaginal ring.

1959 women were enrolled at 7 research centres in South Africa and Uganda Women were randomly assigned to receive the Dapivirine ring or placebo with no active medication and they also received condoms, prevention counselling and HIV testing. Those who enrolled had average of 26 years, very few (9%) were married, nearly all (98%) reported having a primary sex partner and most (91%) had children.
The results showed that Dapivirine vaginal ring resulted in a 31% reduction in the rate of HIV-1 infection compared to the placebo group. After excluding one research centre with lower adherence, the percentage reduction in rate of HIV-1 infection was similar (30%). Women older than 21 years had a much higher HIV-1 protection rate compared to women 21 years and younger. The highest HIV-1 protection was seen in women aged 22 – 25 years old.

Adherence was measured by testing the amount of Dapivirine in blood samples collected every month and used rings collected every month. Trends indicated that higher levels of product adherence resulted in higher levels of protection against HIV-1 infection( as high as 65% HIV-1 infection reduction).

In summary, Dapivirine vaginal ring was safe when used over 2 years. It reduced the transmission of HIV-1 infection via vaginal intercourse by 31% in women in Sub-Saharan Africa. Potential trends show increased protection with increased ring use and will be evaluated further. The Dapivirine ring may be an important HIV prevention option for women at risk of HIV infection.

 

Funder/Sponsor: International Partnership for Microbicides (IPM)
Principal Investigator: Dr C Gama (MatCH Research Unit)
Site: MatCH Research Edendale Site
IPM 032:- A Follow on, Open-Label trial to assess continued Safety of and Adherence to the Dapivirine (25mg) Vaginal Ring-004 in Healthy HIV Negative Women
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been designed as an open-label clinical trial to collect additional safety data and establish adherence to ring use of the Dapivirine (25mg) Vaginal Ring -004 in healthy, HIV-negative women with monthly (at least one to a maximum of three months) followed by 3-monthly research centre follow-up visits over 12 months. The safety results and the level of efficacy observed in IPM 027 and MTN-020 has been communicated to the relevant local and international regulatory authorities, IRBs/IECs, community representatives, participants and key stakeholders, as appropriate before activation of IPM 032. Data collection commenced in August 2016 and will be completed at the end of 2018.

Funder/Sponsor: International Partnership for Microbicides (IPM)
Principal Investigator: Dr C Gama (MatCH Research Unit)
Site: MatCH Research Edendale Site
FACTS 001: A Phase III, Multi-Centre, Randomised Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Human Immunodeficiency Virus Type 1 Infection in Young Women, and to Examine Effects of the Microbicide on the Incidence of HSV-2 Infection
This study (FACTS 001) was designed to confirm the results of the CAPRISA 004 study, which was conducted at two sites in KwaZulu-Natal, South Africa, using a coitally linked regimen, and which demonstrated an overall effectiveness of 39% in preventing HIV-1 infection. This multi-centred study included sexually active women, and was conducted at nine sites in South Africa.   Findings of the study, were reported at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, United States at the end of February 2015. The study enrolled 2 059 sexually-active HIV-negative women, aged 18 – 30 years. The main findings of the study showed that there was no difference in the rate of new HIV infections occurring in the vaginal Tenofovir gel group compared with the placebo group (i.e. there was no evidence that Tenofovir gel was effective in preventing HIV in this population).

Funder/Sponsor: South African Department of Science and Technology, USAID, Bill and Melinda Gates Foundation via Wits Reproductive Health Institute (WRHI)
Site Principal Investigator: Dr D Ntshangase (MatCH Research Unit)
Site: Match Research Edendale Research Site
SILCS Diaphragm: A Randomized Cross-over Study Evaluating the Use and Acceptability of SILCS Diaphragm Compared to Vaginal Applicators for Placebo Gel Delivery
The SILCS Diaphragm is a new single-size, reusable cervical barrier (Fig 1). Since diaphragms are used with contraceptive gel to improve effectiveness, researchers are interested in assessing the SILCS Diaphragm as a delivery system for microbicide gel. The SILCS diaphragm has regulatory approval in Europe, and applications for regulatory approval are underway in the United States and Canada.

 

This study evaluated use and acceptability of the SILCS Diaphragm compared to standard vaginal applicators for delivery of a placebo vaginal gel.  In this randomized crossover study, 115 female participants were randomized to use the SILCS Diaphragm with placebo gel  followed by use of vaginal applicators to deliver placebo gel directly into the vagina, or vice versa. The use and acceptability of both methods of gel delivery was assessed. A sub-sample of male partners were recruited to gather issues of partner acceptability. Fieldwork is now complete and data analysis is in progress.

 

Funder/Sponsor: USAID via Program for Appropriate Technology in Health (PATH)
Principal Investigators: M Beksinska and Prof J Smit (MatCH Research Unit)
Site: MatCH Research Commercial City Site

 

Pubic hair grooming practices: safety issues, association with STIs
Pubic hair grooming, defined as partial or full removal of pubic hair is gaining popularity globally and It is now a common practice among men and women. Recent studies have examined the relationship between demographic and behavioral risk factors associated with pubic hair grooming-related injuries with some finding ever having groomed was positively associated with a history of self-reported STIs.
There is limited information on pubic grooming (hair removal) practice in Africa. This  study aimed to investigate pubic hair grooming practices and the association with pubic hair grooming injuries, with STIs. The results of this analysis were published in 2020.

 

Beksinska, M., Lulie, B., Beesham, I., Smit, J. (2020). Pubic hair grooming practices in KwaZulu-Natal, South Africa: Prevalence, side effects and association with sexually transmitted infections. International Journal of STD and AIDS. 31(11), 1034-1039. https://doi.org/10.1177/0956462420941709 [published online ahead of print, 2020 Aug 4].