The purpose of this study is to refine the content of a combination intervention to promote HIVST for Partners and PrEP uptake for HIV-uninfected Postpartum Women via two focus group discussions (FGDs) conducted with individuals in SA who have had a child in the past year (N = up to 10 women and 10 men).

 

After adapting the intervention, we will conduct a randomized pilot trial of the H4P intervention to evaluate the feasibility, acceptability, and preliminary effectiveness of a multi-step PrEP uptake and HIVST kit intervention for postpartum women who report a partner of unknown serostatus, and their partners, in the province of KZN, SA (which will be submitted as a separate protocol, Phase II).

Study title	Ukubandakanya abesilisisa: HIV self-testing for Partners of HIV-uninfected Postpartum Women to facilitate PrEP and ART uptake to promote HIV treatment and prevention (Aim I)
Funder	National Institutes of Health (US)
Principal and Co-Principal investigators	Dr Christina Psaros – Massachusetts General Hospital  Prof Jenni Smit – Wits MRU  Dr Lynn Mathews – University of Alabama Birmingham
Site	National / Provincial

 

This study aims to identify implementation gaps and challenges related to integration of PrEP for HIV prevention in services where contraception is delivered and develop a strategy on how to address these challenges and enhance scale up.

The study will:- 1. Explore the coverage and readiness of PrEP delivery where contraceptive services are provided. 2. Identify feasibility, facilitating and impeding factors that influence the integration of contraception and PrEP services and sustainability at all levels of care. 3. Explore stakeholders’ knowledge and perceptions towards the integration of contraception and PrEP services. 4. Identify clients’ acceptability, perceived barriers and enablers of receiving PrEP where contraceptive services are provided, in order to understand factors that influence clients’ decision making about PrEP initiation and continuation in the context of integrated service delivery. 5. Draw upon findings to develop a strategy with stakeholders that addresses implementation gaps and challenges and the development of indicators to measure integration of PrEP and contraceptive services.

This study will be conducted in South Africa at multiple levels of organization: national, provincial, district (eThekwini District, KwaZulu-Natal [KZN] Province), primary health facilities, and community.

Study title	Implementation Research on Introducing and Scaling Up Pre-Exposure Prophylaxis Prevention of HIV Infection within Family Planning/Contraceptive Services in South Africa
Funder	WHO
Principal and Co-Principal investigators	Prof Jenni Smit (PI)  Mags Beksinska (Co-PI) Nzwakie Mosery (Co-PI)
Site	National / Provincial

 

 

Study title	Developing a resiliency intervention to support nurses engaged in the provision of HIV care (Phase I)
Study design	This study will adapt, refine, and pilot test an existing stress management and resiliency-enhancing intervention (the Relaxation Response Resiliency Program; 3RP) for nurses providing HIV care in the public sector in SA. We will identify the ways in which the 3RP requires adaptation to meet the needs of nurses based on data collected from focus group discussions (FGDs) and adapt the intervention accordingly. We will enroll N=15-21 nurses to participate in FGDs (up to 3 groups of 5-7 nurses).
Funder	NIH –
Principal investigators	Dr Christina Psaros – Massachusetts General Hospital, Prof Jenni Smit – Wits Maternal Adolescent and Child Health Research
Site	EThekwini clinics providing HIV care

 

This NIH funded  projects is analysing samples collected during the ECHO study. The following aims are:-

 

Aim 1: Analyze the vaginal microbiome of women by 16S rRNA gene survey and metagenomic sequencing.

Aim 2: Evaluate levels of vaginal cytokines and antimicrobial proteins.

Aim 3: Evaluate changes in the frequency and activation of cervical Th17-like and α4β7 CD4+ T cells.

Aim 4: Conduct a discovery metaproteomics analysis, followed by a targeted validation analysis to evaluate alterations in human and microbial proteins.

Aim 5: Evaluate the MPA dose-dependency of changes in the microbiome, cytokines, antimicrobial proteins and target cells, and the effect of systemic and genital hormone levels

 

Data is now in the write up phase.

 

Funder/Sponsors:	NIH via FHI360
Principal Investigator	J.Deese, K.Nanda, C.Morrison, MRU PI Jenni Smit
MRU Sub-Investigators
Site:	Setshaba Research Centre Match Research Unit Commercial City

 

 

This study is being conducted to learn more about young women’s experience using a daily oral pre-exposure prophylaxis or PrEP for the prevention of HIV.   There are two PrEP medications being used in this study. One is called Truvada or F/TDF and has been approved for PrEP by the United States Food and Drug Administration (FDA), and the South African Health Products Regulatory Authority (SAHPRA). Truvada or F/TDF is available as PrEP in South Africa. The other medication is called Descovy or F/TAF and has been approved by the FDA for treatment and as daily PrEP for men but not yet women. It is hoped that, if approved by SAHPRA women will, in the future, be able to use Descovy (F/TAF) as PrEP to prevent HIV transmission. Some participants participating in this study will be asked to use Truvada, others will be asked to use Discovy. Up to  330 adolescent girls and young women in total at three clinical research sites (two in South Africa and one in Zimbabwe)  are expected to enroll. MRU will enrol up  to 110 women will complete the study at this site.

 

Funder/Sponsor:	CONRAD/EVMS
Principal Investigators:	Jenni Smit, Thando Gwetu (MRU)
Site:	MRU, Durban

 

The primary objective of this study is to evaluate the efficacy of lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF) in preventing the risk of human immunodeficiency virus (HIV) infection relative to the background HIV incidence rate.

The study will be conducted in 2 parts: a cross-sectional study (Incidence Phase) and a double-blind, randomized study (Randomized Phase). The Incidence Phase will include initial assessments that will provide an estimate of the concurrent background HIV incidence rate. The Randomized Phase of the study will have a Blinded Phase, a LEN Open-label Extension (OLE) Phase, and a Pharmacokinetic (PK) Tail Coverage Phase.

The primary objective for the Incidence Phase of this study is to estimate the HIV background incidence rate. The primary objectives of the Randomized Phase of this study are to evaluate the efficacy of LEN and F/TAF for HIV pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) at risk of HIV infection.

 

MRU is on of the 18 South African sites taking part in this study which is due to commence enrolment in 2021.

 

Funder/Sponsor:	GILEAD Sciences
Principal Investigator:	Dr Manjeetha Jaggernath
Site:	MRU Commercial City

 

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 was a single-arm longitudinal study that  offered daily oral tenforvir/emtricitabine (TDF/FTC) as a pre-exposure prophylaxis for periconception.  The study enrolled its first participant in November 2017. A total of 330 participants were enrolled into the study, with the last participant exited in May 2021. In the unfortunate occurrence of the COVID-19 pandemic, the study was able to successfully follow-up participants through hybrid study visits where most of activities were conducted telephonically and participants came to site only for clinical study activities.

Following the completion of participants’ follow-up, dissemination and analysis of study findings are currently underway and had successfully completed disseminating findings to study participants in March 2022.

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 presented 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

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 targeted  pregnant women, living with HIV.  Participant are  being followed up  for  a period of two years. Field work commenced in  2018 and enrolment ended on 20 March 2020 having enrolled 472 participants.  Participants are  currently being exited.

An ancillary study investigating the incidence of HIV drug resistance among postpartum Women Living with HIV and failing first-line ART commenced in August 2019. PEPEHC participants are invited to consent to HIV drug resistance testing at 12 months visit on all samples with a viral load >1000 and dried blood spots for Tenofovir DP levels.  

 

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

 

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 been completed and results have been submitted for publication.

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

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 were  developed, and women’s preferences were assessed.

This study aimed to explore women’s preferences and attitudes to different vaginal ring product attributes.  We  conducted three focus group discussions (FGDs)  in eThekwini, in 2021 with  women, aged 18–35, per group. Vaginal rings developed in different sizes, colours and fragrances were shown to women and their opinions on the product attributes and preferences will be discussed. This study has published its findings:-

 

Zhao X, Milford C, Smit J, Zulu B, Boyd P, Malcolm RK, Beksinska M. Color, Scent and Size: Exploring Women’s Preferences Around Design Characteristics of Drug-Releasing Vaginal Rings. AIDS Behav. 2022 Mar 16:1–15. doi: 10.1007/s10461-022-03596-7. Epub ahead of print. PMID: 35294694; PMCID: PMC8924943.

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

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

Site:       MRU, Durban

The MSD IMPOWER-022 trial is a new HIV prevention double-blinded randomised clinical trial that will test the effectiveness and safety of a new monthly oral pre-exposure prophylaxis pill (PrEP). Daily oral PrEP offer women the ability to protect themselves from HIV-1 infection but taking a tablet every day can be onerous. A monthly tablet would reduce the burden of a daily tablet and if found to be effective offer women with an alternative option to protect themselves from HIV-1 infection.

The new monthly oral PrEP tablet will be compared to the standard daily oral PrEP tablet. Women between the ages of 16 and 45 years will be randomised into one of two groups. Group 1 will take the active monthly oral PrEP tablet and a daily placebo tablet, while Group 2 will take a monthly placebo tablet and the active daily oral PrEP tablet. This is a double-blinded clinical trial which means that neither the study staff nor the participants will know which Group they are in. Study participation is for three-years with monthly follow-up visits. Women who become pregnant during the study period will be allowed to continue participating in the trial.

It is hoped that the new monthly oral PrEP tablet will offer women with a practical new solution to prevent HIV-1 infection and aids in the international efforts to end the HIV/AIDS pandemic in our lifetime.

MatCH Research Unit (MRU) is among 21 other sites from South Africa, eSwatini, Kenya, Malawi, Uganda, Zambia and Zimbabwe looking to enrol a total of 3000 sexually active cisgender woman aged 16-30 for the INSIGHT Project. Towards the 3000-women sample size, MRU will contribute 150 women over a period of three months and will follow these women for approximately six months. The INSIGHT project evaluates oral PrEP uptake, persistence, and user rankings of product forgiveness and delivery attributes for long-acting PrEP.

 

 

Funder/Sponsor:	Bill and Melinda Gates Foundation
Principal Investigators:	Jenni Smit, Manjeetha Jaggernath (MRU)
Site:	MRU, Durban

 

 

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

 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 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

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

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 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 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

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

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, 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].