105 results on '"Abdool Karim, Salim S."'
Search Results
2. Durability of Vaccine-Induced and Natural Immunity Against COVID-19: A Narrative Review.
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Pooley, Nick, Abdool Karim, Salim S., Combadière, Behazine, Ooi, Eng Eong, Harris, Rebecca C., El Guerche Seblain, Clotilde, Kisomi, Masoumeh, and Shaikh, Nabila
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NATURAL immunity , *SARS-CoV-2 , *COVID-19 , *ANTIBODY formation , *BREAKTHROUGH infections - Abstract
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 time. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. Both antibody and T/B-cells levels have been investigated as potential correlates of protection post-vaccination or post-infection. The activity of antibodies and T/B-cells provide some potential insight into the underlying causes of waning protection. This review seeks to summarise what is currently known about the waning of protection provided by both vaccination and/or prior infection, as well as the current information on the respective antibody and T/B-cell responses. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Impact of SARS-CoV-2 variants of concern on Covid-19 epidemic in South Africa.
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Abdool Karim, Salim S. and Baxter, Cheryl
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SARS-CoV-2 , *COVID-19 pandemic , *SARS-CoV-2 Delta variant , *CONVALESCENT plasma , *VIRUS diseases , *COVID-19 - Abstract
SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. The Covid-19 pandemic has resulted in immense suffering throughout the world, with over 250 million cases and over 5 million Covid-19-related deaths reported by 9 November 2021. The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines. bioRxiv: the preprint server for biology. Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. medRxiv 2021.08.18.21262237. [Extracted from the article]
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- 2022
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4. COVID-19 in Africa: Catalyzing change for sustainable development.
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Abdool Karim, Salim S., Kelemu, Segenet, and Baxter, Cheryl
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COVID-19 , *SUSTAINABLE development - Abstract
Salim Abdool Karim, Segenet Kelemu and Cheryl Baxter discuss COVID-19 impacts and adaptations in Africa. [ABSTRACT FROM AUTHOR]
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- 2021
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5. New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications.
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Abdool Karim, Salim S and de Oliveira, Tulio
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- 2021
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6. Expert consensus statement on the science of HIV in the context of criminal law.
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Barré‐Sinoussi, Françoise, Abdool Karim, Salim S., Albert, Jan, Bekker, Linda‐Gail, Beyrer, Chris, Cahn, Pedro, Calmy, Alexandra, Grinsztejn, Beatriz, Grulich, Andrew, Kamarulzaman, Adeeba, Kumarasamy, Nagalingeswaran, Loutfy, Mona R., El Filali, Kamal M., Mboup, Souleymane, Montaner, Julio S. G., Munderi, Paula, Pokrovsky, Vadim, Vandamme, Anne‐Mieke, Young, Benjamin, and Godfrey‐Faussett, Peter
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HIV infection transmission , *SEXUAL intercourse , *CRIMINAL justice system , *HIGHLY active antiretroviral therapy , *PHYLOGENY - Abstract
Abstract: Introduction: Globally, prosecutions for non‐disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. Discussion: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV‐negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. Conclusions: The application of up‐to‐date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV. [ABSTRACT FROM AUTHOR]
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- 2018
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7. HIV-1 Epidemic Control - Insights from Test-and-Treat Trials.
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Abdool Karim, Salim S.
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ANTIRETROVIRAL agents , *PRE-exposure prophylaxis , *FALSE positive error , *HIV , *MATHEMATICAL models , *MEDICAL care , *CLUSTER randomized controlled trials , *HIV infections , *DISEASE incidence , *OMEGA-3 fatty acids , *SOCIAL stigma , *EPIDEMICS , *HIV seroconversion , *ANTI-HIV agents - Abstract
The article offers information on the effect of universal testing and treatment on community human immunodeficiency virus (HIV) incidence. It mentions three trials of universal testing and treatment show varying outcomes, from modest to no reductions in HIV incidence; and also mentions three and a half of the four trials of universal testing and treatment did not show significant reductions in HIV incidence.
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- 2019
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8. Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection.
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Abdool Karim, Salim S., Karim, Quarraisha Abdool, Kharsany, Ayesha B. M., Baxter, Cheryl, Grobler, Anneke C., Werner, Lise, Kashuba, Angela, Mansoor, Leila E., Samsunder, Natasha, Mindel, Adrian, and Gengiah, Tanuja N.
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TENOFOVIR , *HERPES simplex prevention , *SEXUALLY transmitted diseases , *HIV infection transmission , *WESTERN immunoblotting , *THERAPEUTICS - Abstract
The article presents a study on the use of tenofovir gel in preventing herpes simplex virus type 2 infections. Topics include the global strategy to prevent and control sexually transmitted diseases of the World Health Organization, the participation of women at the Centre for the AIDS Programme of Research in South Africa (CAPRISA), and the use of the Western blot assay in testing.
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- 2015
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9. Defeating AIDS--advancing global health.
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Piot, Peter, Abdool Karim, Salim S, Hecht, Robert, Legido-Quigley, Helena, Buse, Kent, Stover, John, Resch, Stephen, Ryckman, Theresa, Møgedal, Sigrun, Dybul, Mark, Goosby, Eric, Watts, Charlotte, Kilonzo, Nduku, McManus, Joanne, Sidibé, Michel, UNAIDS-Lancet Commission, and UNAIDS–Lancet Commission
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- 2015
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10. Defeating AIDS—advancing global health.
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Piot, Peter, Abdool Karim, Salim S., Hecht, Robert, Legido-Quigley, Helena, Buse, Kent, Stover, John, Resch, Stephen, Ryckman, Theresa, Møgedal, Sigrun, Dybul, Mark, Goosby, Eric, Watts, Charlotte, Kilonzo, Nduku, McManus, Joanne, and Sidibé, Michel
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AIDS prevention , *HIV prevention , *WORLD health , *PUBLIC health - Abstract
The article highlights the recommendations of the report "Defeating AIDS--Advancing Global Health" by the Joint United Nations Programme on HIV and AIDS (UNAIDS) and the Lancet Commission. They include the expansion of access to AIDS treatment, forging new paths to uphold human rights and address criminalisation, stigma and discrimination, and the evolution of AIDS response in an era of sustainable development. INSETS: Panel 1: Kenya aims to revolutionise HIV prevention.;Panel 2: Beyond the grand convergence.;Panel 3: Development assistance and human rights.;Panel 4: Main findings of this Commission.
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- 2015
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11. Innate Immune Activation Enhances HIV Acquisition in Women, Diminishing the Effectiveness of Tenofovir Microbicide Gel.
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Naranbhai, Vivek, Abdool Karim, Salim S., Altfeld, Marcus, Samsunder, Natasha, Durgiah, Raveshni, Sibeko, Sengeziwe, Abdool Karim, Quarraisha, and Carr, William H.
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HIV-positive women , *HIV-positive persons , *TENOFOVIR , *BACTERICIDES , *DISINFECTION & disinfectants - Abstract
The antiretroviral agent, tenofovir, formulated as a vaginal microbicide gel, reduces human immunodeficiency virus (HIV) acquisition by 39% in women. This study assessed the role of preexisting immune activation in HIV acquisition in women from the CAPRISA 004 trial, to identify potential strategies to increase the effectiveness of tenofovir gel. Systemic cytokine and cellular immune mediators (platelets and natural killer [NK] cells) were assessed in women at high risk for HIV assigned to either tenofovir or placebo gel in the CAPRISA 004 trial. Notwithstanding tenofovir gel use, women who acquired HIV had significantly higher systemic innate immune activation prior to infection than women who remained uninfected. Activation of both soluble (cytokine) and cellular (NK cells) immune mediators were associated with HIV acquisition, individually or in combination. Hence, an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides. [ABSTRACT FROM PUBLISHER]
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- 2012
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12. Integration of Antiretroviral Therapy with Tuberculosis Treatment.
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Abdool Karim, Salim S., Naidoo, Kogieleum, Grobler, Anneke, Padayatchi, Nesri, Baxter, Cheryl, Gray, Andrew L., Gengiah, Tanuja, Gengiah, Santhanalakshmi, Naidoo, Anushka, Jithoo, Niraksha, Nair, Gonasagrie, El-Sadr, Wafaa M., Friedland, Gerald, and Abdool Karim, Quarraisha
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TUBERCULOSIS treatment , *ANTIRETROVIRAL agents , *CLINICAL drug trials , *HIV , *SPUTUM , *IMMUNE reconstitution inflammatory syndrome - Abstract
Background: We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved. Methods: We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here. Results: At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006). Conclusions: Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.) [ABSTRACT FROM PUBLISHER]
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- 2011
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13. Epidemiological Impact of Tenofovir Gel on the HIV Epidemic in South Africa.
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Williams, Brian G, Abdool Karim, Salim S, Karim, Quarraisha Abdool, and Gouws, Eleanor
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Tenofovir gel, an antiretroviral-based vaginal microbicide, reduced HIV acquisition by 39% in women in a recent randomized controlled clinical trial in South Africa.To inform policy, we used a dynamical model of HIV transmission, calibrated to the epidemic in South Africa, to determine the population-level impact of this microbicide on HIV incidence, prevalence, and deaths and to evaluate its cost-effectiveness.If women use tenofovir gel in 80% or more of sexual encounters (high coverage), it could avert 2.33 (0.12 to 4.63) million new infections and save 1.30 (0.07 to 2.42) million lives and if used in 25% of sexual encounters (low coverage), it could avert 0.50 (0.04 to 0.77) million new infections and save 0.29 (0.02 to 0.44) million deaths, over the next 20 years. At US $0.50 per application, the cost per infection averted at low coverage is US $2392 (US $562 to US $4222) and the cost per disability-adjusted life year saved is US $104 (US $27 to US $181); at high coverage the costs are about 30% less.Over 20 years, the use of tenofovir gel in South Africa could avert up to 2 million new infections and 1 million AIDS deaths. Even with low rates of gel use, it is highly cost-effective and compares favorably with other control methods. This female-controlled prevention method could have a significant impact on the epidemic of HIV in South Africa. Programs should aim to achieve gel use in more than 25% of sexual encounters to significantly alter the course of the epidemic. [ABSTRACT FROM AUTHOR]
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- 2011
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14. Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women.
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Abdool Karim, Quarraisha, Abdool Karim, Salim S., Frohlich, Janet A., Grobler, Anneke C., Baxter, Cheryl, Mansoor, Leila E., Kharsany, Ayesha B. M., Sibeko, Sengeziwe, Mlisana, Koleka P., Omar, Zaheen, Gengiah, Tanuja N., Maarschalk, Silvia, Arulappan, Natasha, Mlotshwa, Mukelisiwe, Morris, Lynn, and Taylor, Douglas
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CLINICAL drug trials , *ANTIRETROVIRAL agents , *HIV prevention , *RESEARCH methodology , *BLIND experiment , *RANDOMIZED controlled trials , *PLACEBOS , *AIDS in women - Abstract
The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use. [ABSTRACT FROM AUTHOR]
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- 2010
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15. Timing of Initiation of Antiretroviral Drugs during Tuberculosis Therapy.
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Abdool Karim, Salim S., Naidoo, Kogieleum, Grobler, Anneke, Padayatchi, Nesri, Baxter, Cheryl, Gray, Andrew, Gengiah, Tanuja, Nair, Gonasagrie, Bamber, Sheila, Singh, Aarthi, Khan, Munira, Pienaar, Jacqueline, El-Sadr, Wafaa, Friedland, Gerald, and Abdool Karim, Quarraisha
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TUBERCULOSIS patients , *HIV-positive persons , *MORTALITY , *HIGHLY active antiretroviral therapy , *CLINICAL trials - Abstract
Background: The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial. Methods: In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim–sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause. Results: This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups. Conclusions: The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.) N Engl J Med 2010;362:697-706. [ABSTRACT FROM AUTHOR]
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- 2010
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16. HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response.
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Abdool Karim, Salim S., Churchyard, Gavin J., Abdool Karim, Quarraisha, and Lawn, Stephen D.
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HIV , *TUBERCULOSIS , *EPIDEMICS , *PREVENTIVE medicine , *EPIDEMIOLOGY - Abstract
The article provides information on HIV and tuberculosis epidemics in South Africa and how the government has responded to them. The first cases of AIDS in South Africa occurred in 1982 and the HIV epidemic has evolved through the concentrated epidemic phase, initiation of the generalised epidemic, rapid spread of HIV, and AIDS mortality phase. Tuberculosis was introduced in the 17th century into South Africa by the arrival of European immigrants from Great Britain and the Netherlands. Achievements and innovations in the responses to HIV and tuberculosis are discussed. Steps for HIV and tuberculosis control are outlined.
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- 2009
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17. Informed Consent for HIV Testing in a South African Hospital: Is It Truly Informed and Truly Voluntary?
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Abdool Karim, Quarraisha, Abdool Karim, Salim S., Coovadia, Hoosen M., and Susser, Mervyn
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HIV , *INFORMED consent (Medical law) , *MEDICAL screening , *HIV infection transmission , *MEDICAL ethics - Abstract
Objective. The purpose of this study was to assess informed consent to human immunodeficiency virus (HIV) testing in a perinatal HIV transmission study in a major referral hospital serving a largely Black population in South Africa. Methods. First-time antenatal clinic attenders who were randomly selected from those enrolled in the perinatal HIV study (n = 56) answered questionnaires before and after counseling. Results. Knowledge of HIV transmission and prevention, high at the outset, was little improved after counseling. The acceptance rate for HIV testing was high. Despite assurances that participation was voluntary, 88% of the women said they felt compelled to participate in the study. Conclusions. Informed consent in this setting was truly informed but not truly voluntary. [ABSTRACT FROM AUTHOR]
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- 1998
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18. HIV pre-exposure prophylaxis in injecting drug users.
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Abdool Karim, Salim S.
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TENOFOVIR , *HIV prevention , *INTRAVENOUS drug abusers , *INFECTIOUS disease transmission , *CLINICAL trials , *DISEASES - Abstract
The author discusses research on the efficacy of tenofovir in preventing parenteral transmission of HIV in injecting drug users. He references the study "Antiretroviral Prophylaxis for HIV Infection in Injecting Drug Users in Bangkok, Thailand (the Bangkok Tenofovir Study): A Randomised, Double-Blind, Placebo Controlled Phase 3 Trial." He believes that the findings showed how prophylaxis prevents HIV infection but failed to show how prophylaxis prevents parenteral transmission.
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- 2013
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19. Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women.
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Abdool Karim, Salim S., Kashuba, Angela D. M., Werner, Use, and Karim, Quarraisha Abdool
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AIDS , *ANTIRETROVIRAL agents , *EMTRICITABINE-tenofovir , *PREVENTION of sexually transmitted diseases , *HIV-positive women , *PREVENTION , *DISEASES - Abstract
The article presents a clinical assessment on the effectiveness of topical and oral antiretroviral pre-exposure prophylaxis (PrEP) in treating women with HIV in sub-Saharan Africa. The low pill adherence and inadequate drug concentrations at the site infection explains the inability of oral tenofovir disoproxil fumarate and emtricitabine to prevent women's HIV. The oral dosing of drugs has been observed for its lower drug concentration than the topical application of tenofovir gel.
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- 2011
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20. Stigma impedes AIDS prevention.
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Abdool Karim, Salim S.
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DENIAL (Psychology) , *SOCIAL stigma , *AIDS prevention , *HIV infections , *BEHAVIOR modification , *ANTIRETROVIRAL agents - Abstract
In this article, the author discusses the denial and unawareness expressed by people who are exposed to HIV/AIDS virus in South Africa. According to him, the associated stigma brought by the infection hinders AIDS prevention and treatment, while Africans who volunteer for HIV tests are less. He also highlights the inadequacy of utilizing antiretroviral drugs and disease education for successful AIDS control and suggests behavior modification and fear recognition.
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- 2011
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21. The South African Response to the Pandemic.
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Abdool Karim, Salim S
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- 2020
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22. Obituary: Gita Ramjee (8 April 1956–31 March 2020).
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Abdool Karim, Salim S
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ROLE models , *HIV prevention - Published
- 2020
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23. Effectiveness of ChAdOx1 nCoV-19 and BBIBP-CorV vaccines against COVID-19-associated hospitalisation and death in the Seychelles infected adult population.
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Theresa Pool, Sylvie Nadine, Shroff, Emelyn Helen, Chetty, Agnes, Lewis, Lara, Nonhlanhla, Yende-Zuma, and Abdool Karim, Salim S.
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VACCINATION status , *COVID-19 pandemic , *SARS-CoV-2 Delta variant , *VACCINE effectiveness , *COVID-19 - Abstract
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 Delta variant transmission. Methods: This nationwide retrospective cohort study included all Seychellois residents aged ≥ 18 years who tested positive by RT-PCR or rapid antigen test for COVID-19 between January 25, 2021, and June 30, 2021. We measured the relative risk (RR) of laboratory-confirmed SARS-CoV-2 hospitalisation and/or death among individuals partially or fully vaccinated with ChAdOx1 nCoV-19 (SII Covishield) or BBIBP-CorV (Sinopharm) vaccines compared to unvaccinated individuals using modified Poisson regression. Controlling for age, gender and calendar month, vaccine effectiveness was estimated as 1-RR ≥14 days after the first dose and ≥7 days after the second dose for each available vaccine versus an unvaccinated control group. Results: A total of 12,326 COVID-19 infections were reported in adult Seychellois residents between January 25, 2021, and June 30, 2021. Of these, 1,287 individuals received one dose of either BBIBP-CorV (Sinopharm) or ChAdOx1-nCoV-19 (SII Covishield) vaccine, and 5,225 individuals received two doses. Estimated adjusted effectiveness of two doses of either Sinopharm or SII Covishield was high, at 70% (95% CI 58%–78%) and 71% (95% CI 62%–78%) respectively. Sinopharm maintained high levels of protection against severe outcomes in partially vaccinated individuals at 61% (95% CI 36%–76%), while the effectiveness of one dose of SII Covishield was low at 29% (95% CI 1%–49%). Conclusions: This observational study demonstrated high levels of protection of two doses of two vaccine types against severe outcomes of COVID-19 during the first wave of the pandemic driven by Beta (B.1.351) and Delta (B.1.617.2) variant predominance. One dose of ChAdOx1-nCoV-19 (Covishield SII) was found to be inadequate in protecting the general adult population against hospitalisation and/or death from COVID-19. [ABSTRACT FROM AUTHOR]
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- 2024
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24. The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women.
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Abdool Karim, Salim S, Baxter, Cheryl, Passmore, Jo‐Ann S, McKinnon, Lyle R, and Williams, Brent L
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GENITALIA , *HIV prevention , *BACTERIAL vaginitis , *PRE-exposure prophylaxis , *ANTIRETROVIRAL agents - Abstract
Introduction: Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion: Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a "healthy" vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus‐dominant state to a high‐diversity non‐Lactobacillus‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions: A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition. [ABSTRACT FROM AUTHOR]
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- 2019
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25. Tenofovir Gel to Prevent HSV-2 Infection.
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Abdool Karim, Salim S., Abdool Karim, Quarraisha, and Gengiah, Tanuja N.
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TENOFOVIR , *HERPES genitalis , *HERPES simplex virus - Abstract
A response from the authors of a study about the use of tenofovir gel in treating genital herpes simplex virus type 2 (HSV-2) infection is presented.
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- 2015
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26. Overcoming Impediments to Global Implementation of Early Antiretroviral Therapy.
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Abdool Karim, Salim S.
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ANTIRETROVIRAL agents , *HIV prevention , *PREVENTION of epidemics , *CLINICAL trials , *TREATMENT programs - Abstract
The author reflects on the global implementation of early antiretroviral therapy (ART) to address the human immunodeficiency virus (HIV) epidemic as of August 2015. He cites the long-standing debate on when to start ART in asymptomatic persons, and the viral suppression rates exceeding 95% and 85% of patients initiating ART early in the START and TEMPRANO trials, respectively. The author states that converting these trials into treatment programs will need substantial additional resources.
- Published
- 2015
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27. Identifying SARS-CoV-2 infections in South Africa: Balancing public health imperatives with saving lives.
- Author
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Baxter, Cheryl, Abdool Karim, Quarraisha, and Abdool Karim, Salim S.
- Subjects
- *
SARS-CoV-2 , *CONTACT tracing , *TESTING laboratories , *PANDEMICS , *COVID-19 , *MEDICAL personnel , *PUBLIC health , *HEALTH facilities - Published
- 2021
- Full Text
- View/download PDF
28. HIV—No time for complacency.
- Author
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Abdool Karim, Quarraisha and Abdool Karim, Salim S.
- Subjects
- *
HIV infections , *THERAPEUTICS , *HIV infection risk factors , *HIV-positive persons , *ATTITUDES toward AIDS (Disease) , *SOCIAL stigma , *ANTIRETROVIRAL agents - Abstract
An editorial is presented on the decline in efforts to eliminate HIV. It states that nearly 30 new antiretroviral drugs that are inexpensive, have minimal side effects, and only need be taken once a day have allowed HIV-positive people to live a nearly normal life span. It mentions that despite beliefs the AIDS epidemic is over, nearly 5,000 new cases of HIV infection occur daily and talks about the stigma that HIV-positive people have to live with.
- Published
- 2018
- Full Text
- View/download PDF
29. Mervyn W. Susser - His Contributions to the Acquired Immune Deficiency Syndrome Response in South Africa.
- Author
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Abdool Karim, Salim S.
- Subjects
- *
EPIDEMIOLOGISTS , *SOCIOLOGY methodology , *SURGERY , *ORGANIZATIONAL behavior - Abstract
The article explores the contributions of South African epidemiologist Mervyn W. Susser. Topics discussed include Susser's intellectual independence in issues related to the study of sociology, his works on philosophcal problems of disciplines and his ecologic theory on eco-epidemiology. Other topics include Susser's views on unrealism of Karl Popper and developments in medical surgery methods.
- Published
- 2014
- Full Text
- View/download PDF
30. Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population.
- Author
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Schulz, Vanessa E., Tuff, Jeffrey F., Tough, Riley H., Lewis, Lara, Chimukangara, Benjamin, Garrett, Nigel, Karim, Quarraisha Abdool, Abdool Karim, Salim S., McKinnon, Lyle R., Kharsany, Ayesha B. M., and McLaren, Paul J.
- Subjects
- *
HIV , *SOUTH Africans , *GENETIC variation , *GENOME-wide association studies , *VIRAL variation , *VIRAL load , *CHROMOSOME replication - Abstract
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 alleles. A recent genome-wide association study (GWAS) of HIV VL in individuals of African ancestry identified a locus on chromosome 1, near the protein-coding gene chromodomain helicase DNA-binding protein 1 like (CHD1L), that has a novel association with control of HIV replication. However, not all individuals carrying the protective alleles maintain low VL, and the region’s impact on viral evolution has not been investigated. To address this, we conducted a host-virus regional association analysis in 147 people living with HIV (PLWH) from South Africa with both human and viral genome data available. We observed significant associations between the CHD1L variants rs77029719 (G) (P = 1.6 × 10−2), rs7519713 (T) (P = 2.3 × 10−2), and rs59784663 (G) and 73004025 (T) (P = 1.4 × 10−2) with codon 248 of HIV reverse transcriptase (RT) and between CHD1L variant rs7519713 (T) and codon 18 (P = 3.2 × 10−2) and 147 (P = 3.9 × 10−2) of HIV gag. These associations are consistent with viral escape from CHD1L pressure. In addition, we observed significant associations between HLA B*81 (P = 1.5 × 10−5) and HLA C*18 (P = 7.0 × 10−4) with RT codon 4 and HLAB*58 with RT codon 196 (P = 9.0 × 10−4). This study reveals new evidence of host genetic variation impacting viral evolution in a population highly affected by HIV. IMPORTANCE It has been previously shown that genetic variants near CHD1L on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near CHD1L on HIV RT and gag. Our findings provide further insight into how genetic variability at this locus contributes to host control of HIV in a South African population. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
31. Commentary: Spatial clustering of HIV infection: providing clues for effective HIV prevention.
- Author
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Abdool Karim, Salim S.
- Subjects
- *
HIV infections , *DISEASE prevalence , *MIGRANT labor , *SEX work , *POVERTY - Abstract
The author suggests further investigations on the prevalence of human immunodeficiency virus (HIV) infections along the national road of rural KwaZulu-Natal, South Africa. Factors to consider include age, mobility associated with migrant labour, and prevalence of sex work. Poverty is also discussed as a risk factor in HIV infection. Effective action and intervention on identified HIV communities in South Africa is recommended.
- Published
- 2009
- Full Text
- View/download PDF
32. Tenofovir Gel to Prevent HSV-2 Infection.
- Author
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Feder Jr., Henry M., Abdool Karim, Salim S, Abdool Karim, Quarraisha, and Gengiah, Tanuja N
- Subjects
- *
TENOFOVIR , *HERPES simplex virus , *HERPESVIRUSES , *HERPES genitalis prevention , *ORGANOPHOSPHORUS compounds , *PURINES , *REVERSE transcriptase inhibitors - Abstract
A letter to the editor is presented in response to a study by S. S. Abdool Karim and colleagues which reported that tenofovir gel reduced the acquisition of herpes simplex virus type 2 (HSV-2) in HS2-2 negative women.
- Published
- 2015
- Full Text
- View/download PDF
33. Short course antiretroviral regimens to reduce maternal transmission of HIV.
- Author
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Wilkinson, David, Abdool Karim, Salim S, and Coovadia, Hoosen M
- Subjects
- *
RETROVIRUS disease treatment , *AZIDOTHYMIDINE , *HIV prevention , *JUVENILE diseases ,DEVELOPING countries - Abstract
Editorial. Provides information on the results of an investigation conducted in Bangkok, Thailand which suggested that zidovudine intervention may help prevent HIV infection in children in developing countries. Implication of the results; Reaction to the report; Implementation of the 076 protocol in the United States.
- Published
- 1999
- Full Text
- View/download PDF
34. High Prevalence of Hepatitis B Virus Infection in Rural Black Adults in Mseleni, South Africa.
- Author
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Abdool Karim, Salim S., Thejpal, Rajendra, Singh, Bipraj, Pathol, Clin, and Virol, Clin
- Subjects
- *
HEPATITIS B , *LIVER diseases , *BLACK , *EAR piercing , *DISEASE risk factors , *ETHNOLOGY , *COMMUNITIES - Abstract
Abstract: A community-based study m northern Natal/KwaZulu, South Africa, assessed the prevalence of hepatitis B virus (HBV) infection in rural Black adults. The prevalence of HBV carriers was 4.4 percent in women (N = 342) and 7.1 percent in men (N = 99). At least one marker of HBV infection was present in 81 percent of women and 86 percent of men. The relative risk (RR) of HBV marker positivity in women due to scarification, adjusted for the presence of pierced ears, was 1.37 (95% CI = 0.9, 2.1). Risk factors such as scarification and pierced earlobes need to be further investigated to assess their role in the transmission of the HBV. [ABSTRACT FROM AUTHOR]
- Published
- 1989
- Full Text
- View/download PDF
35. Nelson R. Mandela (1918-2013).
- Author
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Abdool Karim, Salim S.
- Subjects
- *
PRESIDENTS - Abstract
An obituary for South African Anti-apartheid leader and President Nelson Rolihlahla Mandela is presented.
- Published
- 2014
- Full Text
- View/download PDF
36. Pregnancy rates and outcomes in a longitudinal HIV cohort in the context of evolving antiretroviral treatment provision in South Africa.
- Author
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Naicker, Nivashnee, Yende-Zuma, Nonhlanhla, Kharsany, Ayesha B. M., Shozi, Hlengiwe, Nkosi, Duduzile, Naidoo, Anushka, Garrett, Nigel, and Abdool Karim, Salim S.
- Abstract
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 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints.Results: In total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8-2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2-4.8] during HIV infection and 3.7 years (IQR 1.8-5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6-12.9], 48 during established infection [IR 9.3; (CI 6.8-12.3)] and 68 on ART [IR 8.9; (CI: 7.0 - 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004-2009) to 543 cells/µL (2010-2014) and to 696 cells/µL (2015-2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods.Conclusions: Pregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
37. Diverse approaches useful for microbicide trials.
- Author
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Abdool Karim, Salim S. and Abdool Karim, Quarraisha
- Subjects
- *
LETTERS to the editor , *HIV - Abstract
A letter to the editor is presented in response to the article "HIV trial doomed by design" in the 2007 issue.
- Published
- 2007
- Full Text
- View/download PDF
38. Enrolling adolescents in research on HIV and other sensitive issues: lessons from South Africa.
- Author
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Singh, Jerome Amir, Abdool Karim, Salim S., Karim, Quarraisha Abdool, Mlisana, Koleka, Williamson, Carolyn, Gray, Clive, Govender, Michelle, Gray, Andrew, and Karim, Salim S Abdool
- Subjects
- *
ADOLESCENT health , *HIV infections , *MEDICAL research , *CONSENT (Law) , *PARTICIPATION , *RESEARCH ethics , *AGE - Abstract
The article discusses the challenge of enrolling adolescents in HIV studies in South Africa. It is practically impossible in some instances to seek parental consent or to determine who, if anyone, is the legal guardian to authorize an adolescent's participation in research. The South African Medical Research Council research ethics guidelines prescribe 14 years of age as the autonomous age of consent for therapeutic research but not observational studies.
- Published
- 2006
- Full Text
- View/download PDF
39. Medical education after the first decade of democracy in South Africa.
- Author
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Karim SSA and Abdool Karim, Salim S
- Published
- 2004
- Full Text
- View/download PDF
40. Medical education after the first decade of democracy in South Africa.
- Author
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Abdool Karim, Salim S.
- Subjects
- *
APARTHEID , *MEDICAL education , *MEDICAL schools , *MEDICAL students - Abstract
Discusses medical education in South Africa before and after the fall of apartheid. Major changes in medical education in the past ten years; Old admittance system by universities based on race during the apartheid government; Rise in percentage of final year medical students from 1994 to 2001; Dropout rate for African students compared to white students; Current status of the medical community in South Africa.
- Published
- 2004
- Full Text
- View/download PDF
41. Antiretroviral therapy: challenges and options in South Africa.
- Author
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Abdool Karim, Salim S., Abdool Karim, Quarraisha, and Baxter, Cheryl
- Subjects
- *
LETTERS to the editor , *HEALTH policy - Abstract
Presents a letter to the editor about the August 16 Editorial on the decision of South Africa to give the public sector access to antiretroviral therapy in response to the HIV-1/AIDS epidemic.
- Published
- 2003
- Full Text
- View/download PDF
42. Globalization, Ethics, and AIDS Vaccines.
- Author
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Abdool Karim, Salim S.
- Subjects
- *
AIDS vaccines , *HIV , *VACCINES , *TESTING , *ETHICS ,DEVELOPING countries - Abstract
Focuses on ethical concerns about the vaccine trials for HIV infections in third world countries. Quality of vaccines that are used in developing countries; Impact of local conditions on the implementation of ethical standards; Accessibility to a post-trial HIV vaccines.
- Published
- 2000
- Full Text
- View/download PDF
43. Burden of sexually transmitted infections from acute HIV infection among women in South Africa: Evidence from a prospective cohort study.
- Author
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Asare, Kwabena, Osman, Farzana, Ngcapu, Sinaye, Vandormael, Alain, Naicker, Nivashnee, Khanyile, Mlungisi, Mindel, Adrian, Abdool Karim, Salim S., Tomita, Andrew, and Garrett, Nigel
- Subjects
- *
SYPHILIS , *SEXUALLY transmitted diseases , *HIV infections , *NEISSERIA gonorrhoeae , *HIV infection transmission , *CHLAMYDIA trachomatis , *VIRAL load , *SOUTH Africans - Abstract
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 African women.Methods: The CAPRISA002 study enrolled women with acute HIV infection and performed STI testing and treatment 1-2 times annually from 2004-2020. We estimated STI incidence, re-infection, and prevalence trends before and after antiretroviral treatment (ART). We fitted Cox regression models to identify factors associated with STIs.Results: We followed up 235 women (median age = 25 years, IQR 22-29) for 7.5 years (IQR 5.7-10.8). New STI and re-infection cases per 100 person-years (PYs) were 5.1 and 9.5 for Neisseria gonorrhoeae (NG), 7.4 and 14.7 for Chlamydia trachomatis (CT), 8.0 and 26.6 for Trichomonas vaginalis (TV), 7.7 and 16.7 for Mycoplasma genitalium (MG) and 25.2 and 37.3 for any STI. STI incidence, was associated with HIV log10 viral load (AHR = 1.24, 95% CI 1.06-1.44), active syphilis (AHR = 16.55, 95% CI 7.49-36.55), a positive HSV-2 PCR (AHR = 1.54, 95% CI 1.01-2.35), bacterial vaginosis (AHR = 1.48, 95% CI 1.01-2.18), recent regular sexual partners at enrolment (one vs none: AHR = 2.62, 95% CI 1.41-4.87; two plus vs none: AHR = 3.68, 95% CI 1.79-7.59) and age (5-year fold: AHR = 0.80, 95% CI 0.70-0.92).Conclusion: The persistent STI/HIV co-infection burden among South African women highlights that early HIV diagnosis and ART initiation needs to be combined with better STI care for women and their partners to prevent HIV and STI transmission. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
44. Vaginal microbial shifts are unaffected by oral pre-exposure prophylaxis in South African women.
- Author
-
Mazibuko-Motau, Noluthando, Sobia, Parveen, Xu, Jiawu, Elsherbini, Joseph Ahmed, San, James E., Lewis, Lara, Mtshali, Andile, Mzobe, Gugulethu, Ntuli, Lungelo, Abdool Karim, Salim S., Mansoor, Leila E., Abdool Karim, Quarraisha, Kwon, Douglas S., Archary, Derseree, and Ngcapu, Sinaye
- Abstract
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 tenofovir disoproxil fumarate in combination with emtricitabine for PrEP on the vaginal microbiota in South African women. At baseline, Lactobacillus iners or Gardnerella vaginalis dominant vaginal communities were observed in the majority of participants. In cross sectional analysis, vaginal microbiota were not affected by the initiation and use of PrEP. Longitudinal analysis revealed that Lactobacillus crispatus-dominant "cervicotypes 1 (CT1)" communities had high probability of remaining stable in PrEP group, but had a higher probability of transitioning to L. iners-dominant CT2 communities in non-PrEP group. L. iners-dominant communities were more likely to transition to communities associated with bacterial vaginosis (BV), irrespective of PrEP or antibiotic use. As expected, BV-linked CTs had a higher probability of transitioning to L. iners than L. crispatus dominant CTs and this shift was not associated with PrEP use. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies.
- Author
-
Scheepers, Cathrine, Kgagudi, Prudence, Mzindle, Nonkululeko, Gray, Elin S., Moyo-Gwete, Thandeka, Lambson, Bronwen E., Oosthuysen, Brent, Mabvakure, Batsirai, Garrett, Nigel J., Abdool Karim, Salim S., Morris, Lynn, and Moore, Penny L.
- Subjects
- *
CONVERGENT evolution , *MONOCLONAL antibodies , *AIDS vaccines , *IMMUNOGLOBULINS , *HIV , *GERM cells , *GENE targeting - Abstract
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 evolution within these two lineages towards a 111.2GW111.3 motif in the CDRH3 is known to enhance neutralization potency. We have previously isolated an MPER neutralizing antibody, CAP206-CH12, that uses these same germline heavy and light chain genes but lacks breadth (neutralizing only 6% of heterologous viruses). Longitudinal sequencing of the CAP206-CH12 lineage over three years revealed similar convergent evolution towards 111.2GW111.3 among some lineage members. Mutagenesis of CAP206-CH12 from 111.2GL111.3 to 111.2GW111.3 and the introduction of the double GWGW motif into CAP206-CH12 modestly improved neutralization potency (2.5–3-fold) but did not reach the levels of potency of VRC42.01, 4E10 or PGZL1. To explore the lack of potency/breadth, viral mutagenesis was performed to map the CAP206-CH12 epitope. This indicated that CAP206-CH12 is dependent on D674, a highly variable residue at the solvent-exposed elbow of MPER. In contrast, VRC42.01, PGZL1 and 4E10 were dependent on highly conserved residues (W672, F673, T676, and W680) facing the hydrophobic patch of the MPER. Therefore, while CAP206-CH12, VRC42.01, PGZL1 and 4E10 share germline genes and show some evidence of convergent evolution, their dependence on different amino acids, which impacts orientation of binding to the MPER, result in differences in breadth and potency. These data have implications for the design of HIV vaccines directed at the MPER epitope. Author summary: Germline-targeting immunogens are a promising HIV vaccine design strategy. This approach is reliant on the identification of broadly neutralizing antibody (bNAb) classes, which use the same germline antibody genes to target the same viral epitopes. Here, we compare four HIV Envelope MPER-directed antibodies (4E10, VRC42.01, PGZL1 and CAP206-CH12) that despite having shared antibody genes, show distinct neutralization profiles. We show that CAP206-CH12 is dependent on a highly variable residue in the MPER, which results in low neutralization breadth. In contrast, the 4E10, PGZL1 and VRC42.01 mAbs are dependent on highly conserved residues in the MPER, resulting in exceptional neutralization breadth. Our data suggest that while shared germline genes within bNAb epitope classes are required, in some cases these are not sufficient to produce neutralization breadth, and MPER immunogens will need to trigger responses to conserved sites. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Pregnancy rates and outcomes in a longitudinal HIV cohort in the context of evolving antiretroviral treatment provision in South Africa.
- Author
-
Naicker, Nivashnee, Yende-Zuma, Nonhlanhla, Kharsany, Ayesha B. M., Shozi, Hlengiwe, Nkosi, Duduzile, Naidoo, Anushka, Garrett, Nigel, and Abdool Karim, Salim S.
- Subjects
- *
PREGNANCY outcomes , *ANTIRETROVIRAL agents , *HIV infections , *HIV , *VIRAL load , *PRE-exposure prophylaxis - Abstract
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 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints. Results: In total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8–2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2–4.8] during HIV infection and 3.7 years (IQR 1.8–5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6—12.9], 48 during established infection [IR 9.3; (CI 6.8–12.3)] and 68 on ART [IR 8.9; (CI: 7.0 – 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004—2009) to 543 cells/µL (2010–2014) and to 696 cells/µL (2015–2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods. Conclusions: Pregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
47. Prospective study of oral pre‐exposure prophylaxis initiation and adherence among young women in KwaZulu‐Natal, South Africa.
- Author
-
Mansoor, Leila E., Lewis, Lara, Naicker, Cherise L., Harkoo, Ishana, Dawood, Halima, Naidoo, Kalendri, Gengiah, Tanuja N., Samsunder, Natasha, Beesham, Ivana, Abdool Karim, Salim S., and Abdool Karim, Quarraisha
- Subjects
- *
PRE-exposure prophylaxis , *YOUNG women , *HIV prevention , *LONGITUDINAL method , *POISSON regression - Abstract
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 initiation and adherence, and the impact of oral PrEP on HIV incidence in this group. Methods: This prospective cohort study (CAPRISA 082) was conducted at two sites (urban and rural) in KwaZulu‐Natal, between March 2016 and February 2018. HIV‐negative, sexually active women, aged 18–30 years, were enrolled and followed for approximately 10 months. Oral PrEP was offered as part of a comprehensive HIV prevention package. Adherence to oral PrEP was measured using pill counts and tenofovir‐diphosphate (TFV‐DP) levels. Characteristics of oral PrEP initiators versus non‐initiators were compared using risk ratios. HIV incidence rates were measured using Poisson regression. Results: Of 425 women enrolled, 262 (62%) initiated oral PrEP. Uptake was significantly higher at the rural site compared to the urban site (78% [n = 203/259] vs. 36% [n = 59/166], respectively, p‐value<0.001). Approximately 25% and 50% had stopped using oral PrEP by 3 and 12 months post‐initiation, respectively. Median pill count adherence was 90% (interquartile range: 81–97%); however, TFV‐DP was only detected in 13% of samples tested, that is 56/431 samples from 97 (37%) participants who initiated oral PrEP. In total, 11 women seroconverted yielding an HIV incidence rate of 2.81 per 100 person‐years (95% confidence interval: 1.40–5.03). Nine of 11 seroconverters had initiated oral PrEP; however, all showed drug levels equivalent to taking one to zero tablets per week. Among women who initiated oral PrEP, >50% had discontinued using oral PrEP by study end, with side effects, such as diarrhoea, nausea, headaches and rash, being the most frequent reason for discontinuation. Conclusions: Despite moderate oral PrEP initiation and high pill count adherence, adherence as measured by TFV‐DP levels was low and early discontinuation was high. The overall HIV incidence rate was high underscoring the critical need to address barriers to oral PrEP initiation, adherence and continued use, as well as expanding HIV prevention options for young women. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
48. Pre-infection plasma cytokines and chemokines as predictors of HIV disease progression.
- Author
-
Ngcobo, Samukelisiwe, Molatlhegi, Refilwe P., Osman, Farzana, Ngcapu, Sinaye, Samsunder, Natasha, Garrett, Nigel J., Abdool Karim, Salim S., Abdool Karim, Quarraisha, McKinnon, Lyle R., and Sivro, Aida
- Subjects
- *
DISEASE progression , *CHEMOKINES , *HIV infections , *SOUTH Africans , *VIRAL load , *CYTOKINES , *PEAK load - Abstract
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 seroconverted during the CAPRISA 004 tenofovir gel trial. Bio-Plex 200 system was used to measure the expression of 47 cytokines/chemokines in 69 seroconvertors from the CAPRISA 004 trial. Cox proportional hazards regression analyses were used to measure associations between cytokine expression and CD4 decline prior to antiretroviral therapy initiation. Linear regression models were used to assess whether pre-infection cytokine expression were predictors of disease progression outcomes including peak and set-point viral load and CD4:CD8 ratio at less and greater than180 days post infection. Several cytokines were associated with increased peak HIV viral load (including IL-16, SCGFβ, MCP-3, IL-12p40, SCF, IFNα2 and IL-2). The strongest association with peak viral load was observed for SCGFβ, which was also inversely associated with lowest CD4:CD8 ratio < 180 days post infection and faster CD4 decline below 500 cells/µl (adjusted HR 4.537, 95% CI 1.475–13.954; p = 0.008) in multivariable analysis adjusting for age, study site, contraception, baseline HSV-2 status and trial arm allocation. Our results show that pre-infection systemic immune responses could play a role in HIV disease progression, especially in the early stages of infection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. Sensitive Tenofovir Resistance Screening of HIV-1 From the Genital and Blood Compartments of Women With Breakthrough Infections in the CAPRISA 004 Tenofovir Gel Trial.
- Author
-
Wei, Xierong, Hunt, Gillian, Abdool Karim, Salim S., Naranbhai, Vivek, Sibeko, Sengeziwe, Abdool Karim, Quarraisha, Li, Jin-fen, Kashuba, Angela D. M., Werner, Lise, Passmore, Jo-Ann S., Morris, Lynn, Heneine, Walid, and Johnson, Jeffrey A.
- Subjects
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TENOFOVIR , *AIDS prevention , *HIV-1 glycoprotein 120 , *GENITAL diseases , *HIV , *HIV seroconversion , *POLYMERASE chain reaction , *THERAPEUTICS , *BREAKTHROUGH infections - Abstract
The Centre for the AIDS Programme of Research in South Africa 004 (CAPRISA 004) study demonstrated that vaginally applied tenofovir gel is a promising intervention for protecting women from sexually acquiring human immunodeficiency virus (HIV). However, the potential for emergence of tenofovir resistance remains a concern in women who seroconvert while using the gel despite the lack of plasma virus resistance as assessed by population sequencing during the trial. We applied highly sensitive polymerase chain reaction–based assays to screen for tenofovir resistance in plasma and vaginal swab specimens. The absence of mutation detection suggested little immediate risk of tenofovir-resistant HIV-1 emergence and forward transmission in settings in which gel users are closely monitored for HIV seroconversion. [ABSTRACT FROM AUTHOR]
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- 2014
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50. Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy.
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Naranbhai, Vivek, Hill, Adrian V. S., Abdool Karim, Salim S., Naidoo, Kogieleum, Abdool Karim, Quarraisha, Warimwe, George M., McShane, Helen, and Fletcher, Helen
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MONOCYTES , *LYMPHOCYTES , *COMBINATION drug therapy , *HIV-positive persons , *HIV infections , *THERAPEUTICS , *TUBERCULOSIS risk factors , *HEALTH - Abstract
Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases.Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted.Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002).Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis. [ABSTRACT FROM PUBLISHER]
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- 2014
- Full Text
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