More than 20 million people are living with HIV in East and Southern Africa. South Africa is particularly badly affected, with an estimated 86,000 deaths in 2002 and an HIV prevalence of 13.9%.
The burden of HIV is increasingly falling on young women. According to UNAIDS, in sub-Saharan Africa, adolescent girls and young women accounted for more than 77% of new infections among young people aged 15-24 years in 2022. In South Africa, nearly two-thirds of new infections (64%) occur in women and 37% in adolescent girls and young women.
Our work spans the continuum of HIV prevention and care, including the development of ground-breaking prevention interventions and technologies, as well as implementation and scale-up of new innovations.
A particular focus is on novel methods of pre-exposure prophylaxis (PrEP), the pre-emptive use of antiretrovirals to prevent HIV infections. We have worked extensively on clinical studies on new interventions, including the dapivirine vaginal ring and long-acting drugs cabotegravir and lenacapavir. Our Implementation Science directorate is working on scaling these solutions in the public health system in South Africa and elsewhere on the continent.
We are also contributing to studies optimising treatment options for children living with HIV, including those with drug-resistant infections, and pregnant women. We also support the optimisation of novel HIV and TB treatment in mother–infant pairs. We are involved in several clinical trials that are exploring the use of bnAbs to prevent HIV infection. Derived from rare individuals who make antibodies that prevent infection of multiple HIV strains, bnAbs hold great promise as a new approach for HIV prevention.
We have developed and evaluated innovative HIV prevention and treatment service delivery models tailored to the needs of vulnerable populations, including adolescent girls and young women, transgender communities, and sex workers.
By July 2024 our PrEP programmes had initiated over 1 in 5 of the 1 500 000 people who have initiated PrEP in South Africa – more than 330 000 people. We are also working on increasing public health system access to new PrEP methods through market shaping, and expanding services into communities through mobile clinics and non-medical environments.
We work closely with health authorities in South Africa to support the strengthening of HIV prevention and care services. Our combined projects currently manage the HIV treatment of over 650 000 people monthly, which amounts to 1 in 8 of the total number of people living with HIV in South Africa.We are also involved in several clinical trials are exploring the use of bnAbs to prevent HIV infection. Derived from rare individuals who make antibodies that prevent infection of multiple HIV strains, bnAbs hold great promise as a new approach for HIV prevention.
South Africa ranks among the 10 nations responsible for two-thirds of global TB infections. There were an estimated number 280 000 cases in 2022, but only 77% of these were detected and treated; 54 000 people died of TB-related causes. TB and HIV and inextricably linked: people living with HIV comprise more than half of all people diagnosed with TB, and TB poses the greatest threat to their lives.
Our TB research focuses on new prevention tools for TB, including trials of new vaccines. This includes participation in globally important BCG revaccination trials for prevention of infection and a landmark phase III trial of M72/AS01E for prevention of TB disease in adolescents and adults.
We also address the long-standing challenge of designing health systems that improve case detection, improve treatment success rates and optimise use of TB medicines to prevent infection amongst affected people.
PURPOSE 2 Study: A phase 3, double-blind, multicentre, randomised trial evaluating the safety and efficacy of twice-yearly long-acting subcutaneous Lenacapavir and daily oral Emtricitabine/Tenofovir Alafenamide for pre-exposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender non-binary individuals at risk of HIV infection. Rationale Both daily oral emtricitabine/tenofovir…
PURPOSE 1 Study: A double-blinded, multicenter, randomized Phase 3 study aimed at assessing the safety and effectiveness of twice-yearly long-acting subcutaneous Lenacapavir, in combination with daily oral Emtricitabine/Tenofovir Alafenamide, for pre-exposure prophylaxis among adolescent girls and young women vulnerable to HIV infection. Rationale Daily use of F/TDF has proven highly…
HPTN 108 Study: Pausing Antiretroviral Treatment Under Structured Evaluation (PAUSE Study). The HPTN 108 Study, also known as the PAUSE Study, is a Phase 1, randomized, placebo-controlled trial investigating the safety, efficacy and tolerability of the combination of two long-acting broadly neutralizing antibodies (bNAbs), 3BNC117-LS-J and 10-1074-LS-J, in ART-treated adults…
A multi-center, randomized, open-label, noninferiority Trial to evaluate the efficacy and safety of a Single, oral dose of zoliflodacin compared to a Combination of a single intramuscular dose of Ceftriaxone and a single oral dose of azithromycin in the Treatment of patients with uncomplicated gonorrhoea. Rationale There is growing concerns…
Combining HIV Prevention Options With Mental Health Service Delivery For Adolescent Girls (CHOMA). Youth Friendship Bench SA Optimization of the Friendship Bench mental health intervention for adolescent girls and young women in South African PrEP delivery settings -Youth Friendship Bench SA. Rationale The study aims to evaluate two primary outcomes…
VAXART Study: A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single Dose, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of Orally Administered Bivalent GI.1/GII.4 Norovirus Vaccine in Healthy Lactating Females ≥ 18 Years Old and Their Breastfeeding Infants. Rationale Noroviruses (NoVs) are a diverse group of small, nonenveloped, single-stranded…
Evaluation of stepped PrEP adherence support for young South African women using a SMART design. Rationale To evaluate the proportion of young South African women who adhere well to PrEP with regular clinic visits and mHealth interventions alone, the proportion of women who adhere well to PrEP with intensified interventions…
Continued access to etravirine in treatment experienced HIV-1 infected subjects. Rationale The aim of the study is to provide continuous access to ETR for subjects who have completed a clinical study with ETR sponsored by or in collaboration with Janssen Research & Development. Primary Objectives The primary objective is to…
Long-Term Clinical, Immunologic, and Virologic Profiles of Children who Received Early Treatment for HIV. Rationale Early treatment of infants living with HIV offers a unique population in which to investigate long-term clinical, immunologic, and virologic outcomes and to better characterize how early ART impacts HIV infection over time. The overarching…
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal Films. Rationale Topical microbicides play a crucial role in mitigating the risk of HIV transmission through sexual contact by applying them to the genital or rectal mucosa. Among various delivery options, vaginal films stand out as a compelling choice…
Rationale Whilst the Department of Health has made significant gains in the introduction and the scale- of oral pre-exposure prophylaxis as an HIV prevention intervention, at 78% of public PHC facilities support is required to achieve of PHC 100% coverage. In the following 2 years, the department will focus strengthening…
Coalition to Accelerate and Support Prevention Research (CASPR). Rationale The objective of this project is to bolster the development and longevity of an Africa-centered network dedicated to promoting advocacy, policy formulation, regulatory compliance, community involvement, and communication initiatives that facilitate the advancement of biomedical HIV prevention research. Here are the…
Accelerating Program Achievements to Control the Epidemic (APACE). Rationale South Africa is at the forefront of the global AIDS response. Although the country has the world’s largest HIV treatment programme, challenges remain in preventing new infections and reducing morbidity and mortality. In 2017, South Africa’s burden of HIV infection was…
A cohort for evaluation of open-label PrEP delivery and PrEP preferences among African women. Study Objectives Estimate HIV incidence using the recency testing on samples from women who screen out due to HIV infection, as well as assess HIV incidence prospectively in the cohort. Assess the characteristics of women who…
Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drug during Pregnancy and Postpartum. Rationale The predecessor of this study, MPAACT P1026s, gained approval in 2003 and enrolled over 1000 pregnant/postpartum women. It investigated the pharmacokinetics (PK) of more than 25 HIV and TB drugs in these women, resulting in 27 published manuscripts…
A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection. Study Primary Objectives To evaluate the efficacy of oral ISL QM compared to FTC/TDF QD for the prevention of HIV-1…
Values and Preferences for a Novel, Systemic, Injectable Multipurpose Product for HIV and Pregnancy Prevention in Individuals Assigned Female at Birth in the United States (ATN 168: HAPPY) Rationale The HAPPY study aims to evaluate the preferences and values regarding a new injectable Multipurpose Prevention Technology (MPT) for preventing pregnancy…
Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern. Primary Objectives to assess the relative risk of symptomatic COVID-19 in Group 1 (PLWH who are SARS-CoV-2 negative at baseline) who receive a 2-dose mRNA-1273 vaccine regimen vs. in Group 2 (PLWH who are SARS-CoV-2…
Evaluation of Pharmacokinetic drug-drug Interactions between hormonal Contraceptives and doravirine-containing ART among women living with HIV in South Africa (EPIC). Rationale While DOR-containing antiretroviral therapy (ART) has been studied in two large clinical trials, the representation of women, especially African women, has been disproportionately low at only 16-17% and 6-10%,…
Project PrEP: Integrating PrEP into Comprehensive Services for Adolescent Girls and Young Women Rationale Project PrEP is a Unitaid funded project that started in 2018 providing oral PrEP to AGYW as part of a comprehensive SRH package in eight fixed facilities and four mobile clinics in three provinces in South…
Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117- LS-J and 10-1074- LS-J, in Healthy American and African Adults (IAVI C100). Rationale Despite all efforts to increase access to HIV prevention and ART in South Africa, incidence of HIV infection continues to be unacceptably high with an estimated 220…
A Phase 3B randomized, open-label study to assess safety and drug detection of the Dapivirine Vaginal Ring and oral TRUVADA in breastfeeding Mother-Infant Pairs. Rationale This study is to assess the safety, drug detection, adherence, and acceptability of the DPV VR (25mg) administered every four weeks, and the once-daily Truvada…
HPTN 084: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women Rationale PrEP may only reach its full potential for HIV prevention with agents that do not depend on daily or near-daily pill-taking. The development…
Antiretroviral analytical treatment interruption (ATI) to assess immunologic and virologic responses in participants who initiated ART in early HIV infection after having received VRC01 or placebo in HVTN 703/HPTN 081. Rationale Antiretroviral therapy (ART) has greatly improved the health and quality of life for many people with HIV by suppressing…
CATALYST : Access to New HIV Prevention Products to Stop HIV Rationale The CATALYST implementation science study, part of the MOSAIC Project, spans several sub-Saharan African countries (South Africa, Lesotho, Kenya, Zimbabwe, and Uganda). It aims to empower women in these regions to prevent HIV by accelerating the adoption and…
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, and pharmacokinetics of PGDM1400LS alone and in combination with VRC07-523LS and PGT121.414.LS in healthy, HIV uninfected adult participants. Rationale The HVTN 140/HPTN 101 study wants to understand how the body’s immune system responds to a new lab-made antibody against…
An international, Bayesian platform adaptive, randomized, placebo‐controlled trial assessing the effectiveness of candidate interventions in preventing COVID‐19 disease in adults. Primary Objectives To determine the effectiveness of MR (or MMR) vaccine in preventing symptomatic (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain,…
Delivery of Antiretrovirals via Implantable System for Young Children (DAISY) Specific Aim 3. Rationale South Africa reports one of the highest populations of HIV-infected young children and of the 55% of children that receive ART only 67% are virally suppressed. Adherence and retention in care are affected by multiple challenges…
Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and their Infants. Rationale To compare the virologic efficacy and safety of three antiretroviral regimens for HIV-1-infected pregnant women and to compare the safety of these regimens for their infants. Primary…
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV among Adolescent Females – A Sub-study of HPTN 084. Rationale Despite reductions in other age groups, the number of deaths attributable to HIV is rising in the adolescent age group. As with many daily medication regimens,…
A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1 Rationale New antiretroviral drugs (ARVs) are crucial for neonatal use, serving both as HIV transmission prophylaxis and treatment for newborns with HIV. Dolutegravir, a potent ARV with a robust resistance barrier, is widely…
UBOMI BUHLE: Understanding Birth Outcomes for Mothers and Infants, Building Healthcare by Linking Exposures. A South African Pregnancy Exposure Registry focused on improving maternal and newborn healthcare. Rationale As South Africa rolls out new adult and Prevention of Mother-to-Child Transmission (PMTCT) treatment guidelines incorporating dolutegravir (DTG)-based antiretroviral therapy (ART) as…
An adaptive phase I/II randomized placebo-controlled trial to determine safety, immunogenicity and efficacy of non-replicating ChAdOx1 SARS-CoV-2 vaccine in South African adults living without HIV; and safety and immunogenicity in adults living with HIV. Rationale The COVID-19 pandemic has significantly disrupted healthcare systems and economies worldwide. Despite efforts, the virus…
AGYW in South Africa (aged between 15 and 24 years) have the highest HIV incidence, with young women in their early 20s having a four-fold burden compared to their male peers: approximately 1,745 new HIV infections occur in this cohort every week, and one third of teenage girls become pregnant…
South African Male User Research on Acceptability of Implants and Injections (SAMURAI). Rationale Our prior formative research in Cape Town, South Africa, revealed a strong willingness among young people, both male and female, to use injectable and implantable HIV prevention products. Through the iPrevent Discrete Choice Experiment (DCE), our team…
A Phase I, Randomized, Placebo-Controlled Trial to Evaluate the Safety, Antiviral, and Immunomodulatory Effects of Combining Broadly Neutralizing Antibodies 3BNC117-LS-J and 10-1074-LS-J in ART-Treated Adults with HIV in sub-Saharan Africa, during a Monitored Analytical Treatment Interruption Period. Rationale Broadly neutralizing antibodies (bNAbs) have emerged as promising tools in addressing gaps…
Rationale Long-acting products have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen. The development of alternative PrEP products such as the PrEP ring and CAB-LA have expanded alternative biomedical HIV prevention options to increase access to most at-risk individuals. It is important to…
MESA-TB Gates MRI : A Randomized, Placebo-Controlled, Observer-Blind, Phase 2 Study to Evaluate the Safety and Immunogenicity of the Investigational M72/AS01E Mycobacterium tuberculosis (Mtb) Vaccine in Virally Suppressed, Antiretroviral-Treated Participants with Human Immunodeficiency Virus (HIV). Rationale Previous phase 1 and 2 randomized controlled trials have demonstrated that the M72/AS01E vaccine is…
IMPAACT 2017 is a Phase I/II Study of the Safety, Acceptability, Tolerability, and Pharmacokinetics of Oral and Long-Acting Injectable Cabotegravir and Long-Acting Injectable Rilpivirine in Virologically Suppressed HIV-Infected Children and Adolescents. Rationale The IMPAACT 2017 is a Phase I/II study being conducted to establish if adolescents (and later younger children),…
A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral MK-8527 Once Monthly in Participants at Low Risk for HIV-1 Infection The purpose of this study is to assess the safety and tolerance of MK-8527 administered once monthly at doses of 3 mg, 6 mg,…
A Phase 2 Clinical Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Participants With HIV-1, who are 4 Weeks to less than 12 Years of Age and Weigh less than 45 kg. Rationale As in adults, the objective of ART in the pediatric…
A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Adolescents and Children. Rationale The success of HAART and the apparent benefits of maximally suppressed viremia have shifted clinical attention towards ARV agents that optimize long-term…
Maximizing OptionS to Advance Informed Choice for HIV Prevention (MOSAIC). Rationale MOSAIC works across multiple countries to implement user-centered research and research translation efforts to identify, understand, and remove barriers to new product introduction, access, and use; coordinate and provide technical assistance to global, national, and subnational stakeholders to expedite…
MTN-042 is a Phase 3B, randomized, open-label safety and pharmacokinetic trial focusing on the use of the Dapivirine Vaginal Ring (VR) and Oral FTC/TDF during pregnancy. Rationale This multicenter, prospective study aims to assess the safety, adherence, and acceptability of the DPV VR (25 mg) inserted every 4 weeks, along…
A multicentre, open-label, single-arm trial to evaluate the safety, pharmacokinetics and antiviral activity of fostemsavir in combination with optimized background therapy (OBT) in HIV-1 infected children and adolescents who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class antiretroviral (ARV) resistance. Rationale The dose selection of…
Adopting a socio-ecological approach, the programme aims to reduce the incidence of HIV infection and violence among adolescent girls and young women (AGYW) through the provision of SRH and PrEP services through differentiated service delivery at community-based sites. Rationale The USAID funded DREAMS initiative adopts a differentiated service delivery approach…
A Phase 3 trial has been initiated as a randomized, double-blinded, placebo-controlled study to assess the safety, tolerability, and immunogenicity of the Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in pregnant participants living with HIV and their infants. Maternal immunization stands as a promising strategy for preventing infant diseases.…
Rationale Global efforts to scale up new long-acting PrEP options such as the dapivirine vaginal ring (DVR) and long-acting cabotegravir (CAB-LA), are some of the tools being deployed to end AIDS by 2030. These efforts will remain fundamentally curtailed by limited supply and high costs, therefore, it is important to…
Rationale Despite significant progress in expanding antiretroviral therapy (ART) and HIV prevention like PrEP (Pre-exposure prophylaxis), South Africa (SA) remains a focal point of the global HIV epidemic. While there have been reductions in HIV incidence and mortality, challenges persist in effectively implementing HIV prevention and care, posing a major…
Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for Primary HIV Prevention during Pregnancy and Postpartum in Adolescents and Young Women and their Infants Rationale Feasibility, Acceptability and Safety of pre-exposure prophylaxis during Pregnancy and Breast Feeding to establish drug thresholds for optimal adherence when FTC/TDF is administered daily…
Rationale The aim of the study is to provide continuous access to Etravirine (ETR) for individuals who have completed a clinical study with ETR sponsored by or in collaboration with Janssen Research & Development. The primary objective is to continue the provision of ETR for subjects who previously received ETR…
A Phase 1 SARS-CoV-2 Vaccine Study to Assess the Safety and Tolerability of GRT-R912 or GRT-R914 Administered as Prime and/or Boost in Healthy Adult Volunteers Naïve to SARS-CoV-2, SARS-CoV-2 Convalescent Subjects, and People Living with HIV. Rationale This Phase 1 clinical trial will assess the potential of Gritstone’s second-generation COVID-19…
Phase II randomised open label trial of full and half dose J&J Ad26.CoV2.S and Pfizer BNT162b2 booster vaccinations after receiving the J&J Ad26.CoV2.S prime vaccine through the SISONKE phase IIIB implementation study. Rationale The study aims to assess the immunogenicity and effectiveness of boosting strategies for the J&J Ad26.COV2.S vaccine.…
A Randomized , Double -Blinded, Placebo-Controlled Phase 3 Study to assess the Efficacy and safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older. Rationale The development of a vaccine for Coronavirus disease -19 (COVID-19) will be critical for containing the current outbreak and…
South African Population Research Infrastructure Network (SAPRIN): A GRT-INSPIRED Sub Study of COVID-19 Perceptions, Impacts and Seroprevalence Among Residents of Atteridgeville, Melusi and Hillbrow in Gauteng, South Africa Rationale The global COVID-19 pandemic is an exceptional emergency, and presents a serious risk to human health and livelihoods, especially in countries…
Operation Gophelega kicked off in January 2022 and is one of the largest grants Wits RHI has ever received from the US President’s Emergency Plan for AIDS Relief and the US Centers for Disease Control and Prevention. This grant will run over five years. Gophelega is at the heart of…
MOSAIC South Africa is excited to announce the official launch of the CATALYST (Catalyzing Access to New Prevention Products to Stop HIV) Study after months of preparation and anticipation. The launch was held at the Wits RHI Key Populations clinic in Johannesburg on 11 August 2023 and was attended by…
We propose to support early product introduction for the dapivirine ring through the Envision FP mechanism with the express goal of shaping the market and establishing a service delivery platform for future MPT VRs. The activity will be called PROMISE (Preparing for Ring Opportunities through Market Introduction Support and knowledge…
The Microbicide R&D to Advance HIV Prevention Technologies through Responsive Innovation and eXcellence (MATRIX) is a USAID Project initiated in 2022 to Advance the Research and Development of Innovative HIV Prevention Products for Women. MATRIX is implemented and co-led by Magee-Womens Research Institute and Foundation, USA, and Wits RHI. This…
A phase III cluster randomised placebo‐controlled trial to assess the efficacy of preventive therapy in child contacts of multidrug‐resistant (MDR) tuberculosis (TB). Rationale This trial specifically targets children less than five years for two reasons. First, children less than five years are at the highest risk of progressing to TB…
A Phase 2, Randomized, Observer-Blinded Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) with Matrix-M™Adjuvant in People Living with HIV. Rationale Novavax, Inc. is developing recombinant vaccines adjuvanted with the saponin-based Matrix-M adjuvant for the prevention of disease caused by SARS-CoV-2.…
A Randomized, Placebo Controlled, Observer-Blind, Phase IIb Study to Evaluate the Efficacy, Safety, and Immunogenicity of BCG revaccination in Healthy Adolescents for the Prevention of Sustained Infection with Mycobacterium tuberculosis. Rationale The study is focused on evaluating the efficacy, safety, and immunogenicity of Bacillus Calmette-Guerin (BCG) revaccination in healthy adolescents…
IMPAACT 2036/CRAYON (Cabotegravir and Rilpivirine Long-Acting Injections in YOung ChildreN) is a Phase I/II Study of the Safety, Tolerability, Acceptability, and Pharmacokinetics of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living with HIV-1,Two to Less Than 12 Years of Age. Rationale This study will use a mixed-methods approach…
Wits RHI 060 (ADVANCE): A 96-week Randomised, Phase 3 Non-inferiority Study of DTG + TAF + FTC Compared with DTG + TDF + FTC and EFV + TDF+FTC in Patients Infected with HIV-1 Starting First-line Antiretroviral Therapy. Rationale The primary objective of this study is to demonstrate the non-inferiority of dolutegravir (DTG)…
Programmatic Implementation and Technical Assistance (TA) for HIV/AIDS and Tuberculosis (TB) Prevention, Care, and Treatment Services throughout the Health System in South Africa under PEPFAR – SA. Rationale South Africa is at the forefront of the global AIDS response and has made progress in the fight against HIV. Although the…
Abstract
Children living with HIV (CLWH) face unique challenges with adherence to antiretroviral therapy. In South Africa, just over a third of children receiving antiretroviral therapy are virally suppressed. Long-acting, subcutaneous implants may improve outcomes in CLWH compared to current daily oral dosing regimens. Qualitative in-depth interviews and focus group discussions (FGD) were conducted with 50 caregivers of CLHW in Johannesburg, South Africa.