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.

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.

This open-label study will evaluate the effectiveness, safety, and satisfaction of 6-month DMPA SC when injected every six months for 12 months in the abdomen or thigh. Healthy, sexually active women aged 18 to 35 years who are willing to use 6-month DMPA SC as their only means of contraception for 12 months (i.e., 2 injections 6 months apart) with no contraindications for DMPA use will be screened for study eligibility. A total of 710-750 eligible women will be enrolled into the study from three sites (South Africa,  UK, Chili and  the  Dominican Republic.  The primary Efficacy Endpoint will be pregnancy diagnosed by urine pregnancy test and confirmed by serum human chorionic gonadotropin (hCG) and/or ultrasound. The study  commenced in  2022 and aims to be fully enrolled by the end of 2024.

1. What factors facilitate or hinder the implementation of the intervention in the study intervention facilities per country?
2. Was the intervention delivered as intended (per protocol) and did it reach the target audiences of health care providers, duty bearers, citizens and health service users? (Dose, reach and fidelity of the intervention)?

The role of MRU is to co-ordinate and provide support to the research partners conducting the process evaluation research activities in the two countries. MRU is co-ordinating data management and analysis activities for conducting a comprehensive process evaluation.

Female Condom Contraceptive (CoCo) Study

This randomized comparative prospective follow-up study aims to evaluate contraceptive effectiveness of the Cupid, Cupid 2 and FC2  female condoms.   The contraceptive effectiveness will be determined for 6-12 months. The volunteers will be followed-up monthly for up to twelve months. The primary endpoint will be the occurrence of pregnancy or use of emergency contraception, and the diary information will allow pregnancy rates to be characterised by patterns of condom use and failures (contraceptive efficacy and effectiveness rates).  The study commenced enrolment in November 2019 and a total of 400 women took  part in the study which was completed in November 2021. Analysis is in progress.

CUBE: Contraceptive use dynamics beyond the ECHO trial: Assessment of long-term user experiences and method continuation in South Africa

This study is a prospective observational longitudinal study that aims to expand the evidence base on contraceptive method discontinuation by gathering information on method experience, contraceptive use dynamics, and access to long acting reversible contraception removal services following exit from the ECHO trial. The study commenced in December 2018 and  recruited 434 women who have exited the ECHO study on either DMPA, Jadelle implant or the Copper IUD from the MRU Edendale and Commercial City sites. Participants were followed up for  24 months.  The study  obtained information about contraceptive continuation rates, reasons for contraceptive discontinuation, implant and IUD removal outcomes, and barriers to implant and IUD removal access. The study was completed in 2021. An additional COVID component was added to assess the impact of the pandemic on uptake and continuation of contraception. Data analysis and write up is underway.

ECHO Trial (The Evidence for Contraceptive options and HIV Outcomes): A Multi Center, Open-Label, Randomised Clinical Trial Comparing HIV Incidence and Contraceptive Benefits in Women using Depot Medroxyprogesterone Acetate (DMPA), Levonorgestrel (LNG) Implant, and Copper Intrauterine Devices (IUDs).

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This multicentre, open-label, randomised clinical trial sought to compare the risks of HIV acquisition between women randomised to Depot Medroxyprogesterone Acetate (DMPA), Levonorgestrel (LNG) implant, and copper IUDs. The goal of the study was to answer the public health question of the relative risks (HIV acquisition) and benefits (pregnancy prevention) of three commonly-used, effective contraceptive methods among women who desired contraception. Approximately 7,800 sexually active, HIV-negative women not desiring to become pregnant, aged 16-35 years old, seeking effective contraception,  and willing to be randomised to any of the study arms,  were randomly allocated  to one of three study arms in a 1:1:1 ratio: DMPA, LNG, implant, copper IUD.  This study was conducted in 12 sites in Eastern and Southern Africa.   Enrolment  began in December 2015 and the study closed in October 2019, with a total of 7,830 participants completing between 12-18 months of follow-up.  

Data analysis was completed in June 2019 and results were publicly released at the 9^th SA AIDS Conference in Durban South Africa and published in July 19. https://www.ncbi.nlm.nih.gov/pubmed/31204114

Key Findings:                                                                                                                                                       The ECHO Study found no substantial difference in the risk of getting HIV among 7 829 women randomly assigned to use one of three reversible, highly effective contraceptives:

• DMPA-IM
• copper IUDs
• LNG implants

For more information on ECHO study visit: http://echo-consortium.com/

This cross sectional study  explored reasons for requesting removal of Implanon implants, and patterns of contraceptive use among women presenting to an urban reproductive health clinic.

Beesham, I., Smit, J., Beksinska, M., Panday, M., Makatini, V., Evans, S. (2019). Reasons for requesting removal of the hormonal implant, Implanon NXT at an urban reproductive health clinic in KwaZulu-Natal, South Africa. South African Medical Journal (SAMJ) 109(10):750-755. https://doi.org/10.7196/SAMJ.2019.v109i10.12

The WHICH  study aims to provide robust evidence to inform clinicians, policy-makers, and women about the relative risks and benefits of NET-EN versus DMPA IM with respect to biological, physiological, hormonal, psychological and behavioural effects, and method continuation. The WHICH study was a randomised  trial conducted at 2 research sites i.e. the MRU Commercial City site located in Durban and the ECRU site located in East London. In South Africa.    The study commenced  in 2018 and data collection was completed in 2019. Data analysis is  currently underway.

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A Functional Performance Study of The Wondaleaf Female Condom

Following a pilot function  study in 2017, this main function study was  a two-period, cross-over randomized  trial to determine the functional performance, safety and acceptability of the Wondaleaf female condom in comparison to the FC2 female condom.

220 women were enrolled into the study. Each woman was asked to use five Wondaleaf FCs and five FC2  female condoms  (available in the South African public sector). Women were asked to complete a Condom Log at home which gathered data on experience after use of each condom Function, safety, and acceptability was assessed at two follow-up visits approximately one month apart after enrolment. Data collection was completed in Oct 2019 and data analysis is underway.

 Results are expected in the 1^st quarter of 2020

A health sector and community-based participatory approach in a human rights framework, to increase met needs for contraception: The UPTAKE Project

The UPTAKE Project is multi-country complex designed intervention using a community and health care provider participation approach in the provision of family planning and contraceptives. The study objective is to increase met needs for family planning/contraception, through the development, implementation and testing of an intervention involving community and health care provider participation within a human rights framework. The study is being conducted in Kenya, South Africa and Zambia. Formative work has been undertaken to understand perceptions of quality of care and barriers and enablers to accessing family planning methods and services. An intervention package is being developed and refined based on findings from the formative phase, using the theory of change model.

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 is 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 African 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 will be 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 and is currently in a dissemination phase.

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].

During the ECHO study participants were randomised to one of three effective contraceptive methods i.e. the Copper IUD, the Jadelle implant and DMPA. At the final ECHO visit, participants were given a choice of remaining on their contraceptive method or switching to another method. This study looked at reasons for contraceptive method discontinuation at the final ECHO visit; and retrospectively ascertained contraceptive method preferences at randomisation. In addition, participants were contacted approximately 6 months after the ECHO study ended to find out if the participant has changed their contraceptive method since study exit and why. 

This  ECHO ancillary study examined weight changes in women using three contraceptive methods: DMPA, Jadelle Implant and Copper IUD. In this study weight is measured at baseline and then 3 monthly for the duration of follow up in the main ECHO study. Weight gain is commonly cited as a side effect of hormonal contraceptives and is a frequent reason given for discontinuation. The quality of current evidence is considered low, due to a lack of randomization and high loss to follow-up or early discontinuation. This study has  provided high quality evidence on the weight change debate and is ideally placed to examine weight change differences between the three methods, the effect of baseline BMI on future weight change and if early weight gain predicts further weight gain. It will also look at what leads to weight gain such as potential changes in appetite. The results have been submitted to a journal for publication.