Salim S Abdool Karim

• MBChB, MMed, FFPHM, DipData, MSc, PhD
• Managing Director at CAPRISA

Background Tuberculosis (TB) mortality remains persistently high, despite global TB control efforts. The aim of this study was to assess if a quality improvement (QI) intervention reduced deaths in TB patients accessing primary healthcare (PHC) services. Methods In this pre specified secondary analysis of a cluster-randomized controlled study cond...

Introduction Long‐acting HIV pre‐exposure prophylaxis promises to improve uptake, adherence and persistence challenges experienced with daily oral tablets. We assessed the acceptability of an annual tenofovir alafenamide (TAF) implant in South African women enrolled from 9 July 2020 until 31 May 2022 in a Phase I trial. Methods Six women received...

HIV-1 persists as a latent reservoir during suppressive antiretroviral therapy (ART). Viral rebound occurs upon ART interruption, posing a challenge to cure efforts. Characterizing viral populations fuelling rebound is imperative to curing HIV-1. We used longitudinal samples collected pretherapy from women in the CAPRISA 002 cohort to create an evo...

Previous studies have shown that the majority of long-lived cells harboring persistent HIV-1 proviral genomes originates from viruses circulating in the year prior to antiretroviral therapy (ART) initiation, but a smaller proportion originates from viruses circulating much earlier in untreated infection. These observations suggest that discrete bio...

The heavy chain of an antibody is crucial for mediating antigen binding. IGHV genes, which partially encode the heavy chain of antibodies, exhibit vast genetic diversity largely through polymorphism and copy number variation (CNV). These genetic variations impact population-level expression levels. In this study, we analyzed expressed antibody tran...

Enhancing the clinical trial capabilities within Africa is essential to augment the continent’s pandemic prevention, preparedness and response efforts. Here, we describe the critical challenges of clinical trials in Africa and draw upon the lessons learnt from the Consortium for COVID-19 Vaccine Clinical Trials (CONCVACT) experience, such as the im...

Last month, when the world’s most populus country, India, reported its first case of the new, highly transmissible clade Ib mpox variant, the challenge of containing the virus was once again evident. Only a few weeks before that in August, the World Health Organization (WHO) and the Africa Centres for Disease Control and Prevention (Africa CDC) dec...

In this Viewpoint, 2024 Lasker-Bloomberg Public Service Award winners Quarraisha Abdool Karim and Salim S. Abdool Karim discuss their journey in AIDS research in South Africa and the local and global health impact of this research.

Background and objective Saliva has been proposed as a potential more convenient, cost-effective, and easier sample for diagnosing SARS-CoV-2 infections, but there is limited knowledge of the impact of saliva volumes and stages of infection on its sensitivity and specificity. Methods In this study, we assessed the performance of SARS-CoV-2 testing...

Acute, transient lymphocytopenia, not clinically significant was observed in the CAPRISA 012B phase 1 clinical trial following administration of broadly neutralizing antibodies (bnAb)-CAP256V2LS alone or with VRC07-523LS. Lymphocytopenia was assigned upon a > 50% decline in absolute lymphocyte counts following bnAb administration. We posited that s...

Background The Seychelles COVID-19 vaccination campaign was initiated using two different vaccines during the first wave of the pandemic in 2021. This observational study estimated vaccine effectiveness against severe outcomes (hospitalisation and/or death) from individuals infected with COVID-19 in the Seychelles adult population during Beta and D...

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We asse...

People with HIV-1 (PWH) on antiretroviral therapy (ART) can maintain undetectable virus levels, but a small pool of infected cells persists. This pool is largely comprised of defective proviruses that may produce HIV-1 proteins but are incapable of making infectious virus, with only a fraction (~10%) of these cells harboring intact viral genomes, s...

One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequenc...

Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cel...

Background Saliva has been proposed as a potential more convenient, cost-effective, and easier sample for diagnosing SARS-CoV-2 infections, but there is limited knowledge of the impact of saliva volumes and stages of infection on its sensitivity and specificity. Methods In this study, we evaluated the performance of SARS-CoV-2 testing in 171 saliv...

Background For women living with HIV (WLHIV), co-infection with herpes simplex virus type 2 (HSV-2) causes severe genital ulcers and presents additional challenges for their HIV care. To inform preventive strategies, we aimed to determine the incidence and risk factors of HSV-2 positivity in a prospective cohort of South African women. Methods The...

There is variability in viral load (VL) among individuals with untreated human immunodeficiency virus (HIV) infection, and this variability can be partly attributed to host genetics. HIV is known to develop escape mutations to evade host immune pressure, particularly from HLA alleles and, in some cases, counteracts the protective effect of host all...

Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties...

Introduction Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV preven...

To design effective vaccines and other immune interventions against a pathogen, it is necessary to know which aspect of immunity associates with protection. We investigated whether neutralizing antibodies associate with infection clearance in long-term SARS-CoV-2 infection during HIV-mediated immunosuppression. We monitored neutralizing antibody ac...

Background Rapid antigen tests detecting SARS-CoV-2 were shown to be a useful tool in managing the COVID-19 pandemic. Here, we report on the results of a prospective diagnostic accuracy study of four SARS-CoV-2 rapid antigen tests in a South African setting. Methods Rapid antigen test evaluations were performed through drive-through testing centre...

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammati...

Although significant progress has been made in achieving goals for COVID-19 vaccine access, the quest for equity and justice remains an unfinished agenda. Vaccine nationalism has prompted calls for new approaches to achieve equitable access and justice not only for vaccines but also for vaccination. This includes ensuring country and community part...

Introduction Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metfo...

The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators and industry to overcome traditional challenges for the development of vaccine candidates and to reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical development and regulat...

Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a ‘multiple shots on goal’ approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible,...

Background: Concerns around accuracy and performance of rapid antigen tests continue to be raised with the emergence of new SARS-CoV-2 variants. Objective: To evaluate the performance of two widely used SARS-CoV-2 rapid antigen tests during BA.4/BA.5 SARS-CoV-2 wave in South Africa (May - June 2022). Study design: A prospective field evaluatio...

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and publ...

Background: Young women in sub-Saharan Africa continue to bear a high burden of HIV infection. Combination anti-HIV monoclonal antibodies are a potential HIV prevention technology that could overcome adherence challenges of daily oral pre-exposure prophylaxis. In this phase 1 clinical trial we aimed to determine the safety and pharmacokinetic prof...

Purpose: Bacterial vaginosis (BV) facilitates sexually transmitted infection (STI) transmission and is more common among women living with Human Immunodeficiency Virus (WLHIV). Limited evidence exists on the temporal dynamics of BV during HIV infection to inform interventions. This study investigated the incidence, recurrence, prevalence, and risk...

Vaccines developed against SARS-CoV-2 have proven to be highly effective in preventing symptomatic infection. Similarly, prior infection with SARS-CoV-2 has been shown to provide substantial protection against reinfection. However, it has become apparent that the protection provided to an individual after either vaccination or infection wanes over...

Background: Rapid antigen tests detecting SARS-CoV-2 are being increasingly used across the globe and were shown to be a useful tool in managing the COVID-19 pandemic. The purpose of this prospective study was to characterise the performance of four SARS-CoV-2 rapid antigen tests in a South African setting. Methods: Rapid antigen test evaluations w...

Background: This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. Methods: Data from South Africa's national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were...

The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS-CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death...

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 r...

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 r...

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19...

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 r...

Background. Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory–based testing on STI treatment initiation and STI adverse event (STI-AE) reporting. Methods. We used Kaplan-Meier a...

Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies hav...

Vaginal microbiota have been shown to be a modifier of protection offered by topical tenofovir in preventing HIV infection in women, an effect not observed with oral tenofovir‑based pre‑exposure prophylaxis (PrEP). It remains unclear whether PrEP can influence the vaginal microbiota composition. This study investigated the impact of daily oral teno...

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize >80% of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (IGHV1-69 and IGKV3-20) and form a bNAb epitope class. Furthermore, convergent evolutio...

Introduction: The Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. Methods: Data...

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vacc...

We evaluated the performance of nasal and nasopharyngeal Standard Q COVID-19 Ag tests (SD Biosensor) and the Panbio COVID-19 Ag Rapid Test Device (nasal, Abbott) against the Abbott RealTime SARS-CoV-2 assay during the Omicron (21 M, 21K and 21L) wave in South Africa. Overall, all evaluated tests performed well with high level of sensitivity (rangin...

Purpose HIV and other sexually transmitted infections (STIs) often co-occur. However, less evidence exists on the long-term STI dynamics among persons living with HIV in sub-Saharan Africa to inform interventions. We investigated the incidence, prevalence and factors associated with STIs, starting from acute HIV infection in a cohort of South Afric...

Background: In South Africa, women continue to face a high burden of Human Immunodeficiency Virus (HIV) infection and the possible complications thereof during pregnancy. We assessed pregnancy incidence rates and outcomes in a longitudinal HIV cohort study over a 15-year period. Methods: We evaluated pregnancies among women ≥ 18 years between 20...

Introduction: Oral tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis (PrEP), introduced into South Africa (SA) in 2016, has increasingly become part of HIV prevention standard of care. Given the urgent need for increased HIV prevention efforts for young women in SA, we conducted an implementation study to explore oral PrEP initi...

Induction of broadly neutralizing antibodies (bNAbs) to HIV and other diverse pathogens will likely require the use of multiple immunogens. An understanding of the dynamics of antibody development to multiple diverse but related antigens would facilitate the rational design of immunization strategies. Here, we characterize, in detail, the developme...

The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both 1,2 . Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V...

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. We measured SARS-CoV-2 variant neutralization capacity in 39 Omicron sub-lineage BA.1 infected individuals in South Africa starting at a median of 6 (IQR 3-9) days post-symptoms ons...

Background: Up to the end of January, 2022, South Africa has had four recognisable COVID-19 pandemic waves, each predominantly dominated by one variant of concern: the ancestral strain with an Asp614Gly mutation during the first wave, the beta variant (B.1.351) during the second wave, the delta variant (B.1.617.2) during the third wave, and lastly...

Omicron (B.1.1.529) shows extensive escape from vaccine immunity, although vaccination reduces severe disease and death. Boosting with vaccines incorporating variant spike sequences could possibly broaden immunity. One approach to choose the variant may be to measure immunity elicited by vaccination combined with variant infection. Here we investig...

While Covid-19 created unprecedented transparency with real-time reporting across the globe, the pandemic’s politically charged environment made public communication of scientific information particularly challenging. Scientists, as authoritative voices, were thrust into the public eye to explain the evidence amid uncertainty, a changing virus, dis...

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10 and VRC42.01, can neutralize >95% of viruses. These two MPER-directed monoclonal antibodies share germline antibody genes ( IGHV1-69 and IGKV3-20) and form a bNAb epitope class. Furthermore, convergent evolution within...

Background: Undiagnosed asymptomatic subclinical tuberculosis (TB) remains a significant threat to global TB control and accounts for a substantial proportion of cases among people living with HIV/AIDS (PLWHA). We determined the incidence, progression, and outcomes of subclinical TB in anti-retroviral therapy (ART) accessing PLWHA with known previ...

The ongoing COVID-19 pandemic has highlighted the urgent need for a nimble cross-sectoral global data sharing framework that is standardised, ethical, reliable, and accessible by all countries and governed by a trusted international organisation. This communiqué lays out the need for and role of such a trustworthy framework with recommendations on...

The emergence of Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections¹. We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect ce...

Tenofovir-based pre-exposure prophylaxis (PrEP) revolutionized the global HIV prevention landscape. Prior to the proof-of concept trial in 2010, which demonstrated that tenofovir (TFV) could prevent sexual transmission of HIV, prevention options were largely limited to behavior change, condoms, and circumcision. Several subsequent studies evaluatin...

Background Clinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa. Methods Weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each...

Previous studies have highlighted the role of pre-infection systemic inflammation on HIV acquisition risk, but the extent to which it predicts disease progression outcomes is less studied. Here we examined the relationship between pre-infection plasma cytokine expression and the rate of HIV disease progression in South African women who seroconvert...

Genital inflammation (GI) undermines topical HIV pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4+ T cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficac...

Introduction: Effective, long-acting prevention approaches are needed to reduce HIV incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa. Methods: CAPRISA 012A was a randomised, double-blinded, placebo-control...

Background HIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa. Methods An open-label cluster randomized controlled study was conducted...

properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa, infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convale...

Introduction Young African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution. Methods and analysis CAPRISA 018 is a pha...

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated wheth...

The emergence of Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect ce...

Background People living with HIV (PLWH) have been reported to have a higher risk of more severe Covid-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutra...

The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only o...

Inflammatory cytokines augment humoral responses by stimulating antibody production and inducing class-switching. In women, genital inflammation (GI) significantly modifies HIV risk. However, the impact of GI on mucosal antibodies remains undefined. We investigated the impact of GI, pre-HIV infection, on antibody isotypes and IgG subclasses in the...

Salim Abdool Karim, Segenet Kelemu and Cheryl Baxter discuss COVID-19 impacts and adaptations in Africa.

Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive approach to demonstrate the importance of this re...

This chapter traces the history of human immunodeficiency virus (HIV) from its origins, remarkable scientific advances, and unprecedented global responses through to the current state of the epidemic, progress towards ending acquired immunodeficiency syndrome (AIDS) and remaining challenges. It explains the origins of HIV-1 and HIV-2, the developme...