Caprisa (Centre for the Aids programme of research in South Africa)
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Item A pilot study of once-daily antiretroviral therapy integrated with Tuberculosis directly observed therapy in a resource-limited setting.(Lippincott Williams & Wilkins., 2003) Jack, Christopher.; Lalloo, Umesh Gangaram.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; El-Sadr, Wafaa M.; Cassol, Sharon.; Friedland, Gerald H.To determine the feasibility and effectiveness of integrating highly active antiretroviral therapy (HAART) into existing tuberculosis directly observed therapy (TB/DOT) programs, we performed a pilot study in an urban TB clinic in South Africa. Patients with smear-positive pulmonary TB were offered HIV counseling and testing. Twenty HIV-positive patients received once-daily didanosine (400 mg) plus lamivudine (300 mg) plus efavirenz (600 mg) administered concomitantly with standard TB therapy Monday to Friday and self-administered on weekends. After completing TB therapy, patients were referred to an HIV clinic for continued treatment. At baseline, patients had a mean CD4 count of 230 cells/mm3 (range: 24–499 cells/mm3) and a mean viral load of 5.75 log10 (range: 3.81–7.53 log10). Seventeen completed combined standard TB and HIV therapy; 16 of 20 (80%) patients enrolled and 15 of 17 (88%) patients completing standard TB therapy achieved a viral load <50 copies/mL and mean CD4 count increase of 148 cells/mm3. TB was cured in 17 of 20 (85%) enrolled patients and 17 of 19 (89%) patients with drug-sensitive TB. Treatment was well tolerated, with minimal gastrointestinal, hepatic, skin, or neurologic toxicity. The project was well accepted and integrated into the daily TB clinic functions. This pilot study demonstrates that TB/DOT programs can be feasible and effective sites for HIV identification and the introduction and monitoring of a once-daily HAART regimen in resource-limited settings.Item HIV vaccines and immunity.(Allergy Society of South Africa., 2003) Abdool Karim, Salim Safurdeen.; Baxter, Cheryl.No abstract available.Item Multidrug-resistant Tuberculous Meningitis in KwaZulu-Natal, South Africa.(The Infectious Diseases Society of America., 2003) Patel, Vinod B.; Padayatchi, Nesri.; Bhigjee, Ahmed Iqbal.; Allen, J.; Bhagwan, B.; Moodley, A. A.; Mthiyane, T.Multidrug-resistant (MDR) pulmonary tuberculosis (TB) is well described in the literature. Reports of MDR TB meningitis (MDR-TBM), however, are limited to case reports and a single case series. During the period of 1999-2002, 350 patients with TBM were identified by cerebrospinal fluid culture for TB. Thirty patients (8.6%) had TB that was resistant to at least isoniazid and rifampicin. All 30 patients were included in this study. We reviewed hospital charts of the patients with MDR-TBM and describe our experience. Seventeen patients with MDR-TBM died, and, of those who were known to be alive, many experienced significant morbidity. Eighteen patients were HIV positive. Twenty-two patients had been treated for TB in the past, 3 patients had received no previous treatment for TB, and the history of TB treatment was unknown for 5 patients. The study highlights the prevalence of MDR-TBM and identifies new challenges in the management of affected patients.Item Antiretroviral therapy : challenges and options in South Africa.(Elsevier., 2003) Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Baxter, Cheryl.No abstract available.Item The impact of incident and prevalent herpes simplex virus-2 infection on the incidence of HIV-1 infection among commercial sex workers in South Africa.(Lippincott Williams & Wilkins., 2004) Ramjee, Gita.; Williams, Brian G.; Gouws, Eleanor.; Van Dyck, Eddy.; De Deken, Benedicte.; Abdool Karim, Salim Safurdeen.This study investigated the impact of prevalent and incident HSV-2 infection on the incidence of HIV-1 infection in a cohort of female commercial sex workers in KwaZulu-Natal, South Africa. Prior to a vaginal microbicide trial, 416 women were screened for antibodies to HIV-1 and herpes simplex virus-2 (HSV-2) infections and a questionnaire was used to establish behavioral, social, and demographic characteristics. A total of 187 HIV-1-seronegative women were followed up at monthly intervals when blood was drawn and used to detect HIV-1 and HSV-2 antibodies. The median duration of follow-up was 2.2 years. At screening 50% of the women were HIV-1 seropositive and 84% were HSV-2 seropositive. The hazards of HIV-1 among women who were HSV-2 seropositive or seronegative throughout, or among those who seroconverted during the study, were not significantly different. When HSV-2 seroconversion was analyzed as a time-dependent covariate, the hazard ratio for HIV-1 seroconversion was 6.0 (95% CI: 2.6–14.0) times greater among women with incident than among women with prevalent HSV-2 infections. Drawing on other recent studies these data suggest that incident HSV-2 infection increases the risk of HIV-1 infection; the effect wanes with time since infection; and the effect is significantly greater for men than it is for women.Item Item Genocide: burden of proof and inaction is costing lives in Sudan.(Elsevier, 2004) Singh, Jerome Amir.No abstract available.Item Medical education after the first decade of democracy in South Africa.(Elsevier., 2004) Abdool Karim, Salim Safurdeen.No abstract available.Item HIV treatment in South Africa: overcoming impediments to get started.(Elsevier, 2004) Abdool Karim, Quarraisha.No abstract available.Item Health research and human rights in South Africa.(Elsevier, 2004) Singh, Jerome Amir.No abstract available.Item Utility of Tuberculosis directly observed therapy programs as sites for access to and provision of antiretroviral therapy in resource-limited countries.(The Infectious Diseases Society of America., 2004) Friedland, Gerald H.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Jack, Christopher.; Gandhi, Neel R.; El-Sadr, Wafaa M.; Lalloo, Umesh Gangaram.The overwhelming share of the global human immunodeficiency virus (HIV) infection and disease burden is borne by resource-limited countries. The explosive spread of HIV infection and growing burden of disease in these countries has intensified the need to find solutions to improved access to treatment for HIV infection. The epidemic of HIV infection and acquired immune deficiency syndrome (AIDS) has been accompanied by a severe epidemic of tuberculosis. Tuberculosis has become the major cause of morbidity and mortality in patients with HIV disease worldwide. Among the various models of provision of HIV/AIDS care, one logical but unexplored strategy is to integrate HIV/AIDS and tuberculosis care and treatment, including highly active antiretroviral therapy, through existing tuberculosis directly observed therapy programs. This strategy could address the related issues of inadequate access and infrastructure and need for enhanced adherence to medication and thereby potentially improve the outcome for both diseases.Item Ten-year review of research in South Africa : government is tackling the R&D crisis caused by a shift of focus to service delivery.(Nature publishing Group., 2004) Singh, Jerome Amir.No abstract available.Item Recommendations for the design and use of standard virus panels to assess neutralizing antibody responses elicited by candidate Human Immunodeficiency Virus Type 1 vaccines.(American Society for Microbiology., 2005) Mascola, John R.; D'Souza, Patricia.; Gilbert, Peter B.; Hahn, Beatrice H.; Haigwood, Nancy L.; Morris, Lynn.; Petropoulos, Christos J.; Polonis, Victoria R.; Sarzotti, Marcella.; Montefiori, David Charles.No abstract available.Item Early sexual debut among young men in rural South Africa: heightened vulnerability to sexual risk?(BMJ publishing group., 2005) Harrison, Abigail.; Cleland, J.; Gouws, Eleanor.; Fröhlich, Janet Ann.Objective: This report examines early sexual debut (3 partners in the past 3 years (OR = 10.26, p<0.01). Conclusions: Men who initiate sex before age 15 form a distinct risk group in this setting. Specific interventions are needed for young men in the preteen years, before sexual debut.Item Patients’ readiness to start highly active antiretroviral treatment for HIV.(BMJ publishing group., 2005) Gebrekristos, Hirut T.; Mlisana, Koleka Patience.; Abdool Karim, Quarraisha.Assessing whether patients are ready to start antiretroviral treatment may improve HIV prevention and treatment outcomes.Item HIV prevention and treatment research in sub-Saharan Africa: where are the adolescents?(Lippincott Williams & Wilkins., 2005) Naranbhai, Vivek.; Abdool Karim, Quarraisha.No abstract available.Item The abandoned trials of pre-exposure prophylaxis for HIV : what went wrong?(Plos., 2005) Singh, Jerome Amir.; Mills, Edward J.Discusses the impact of irresponsible reporting and activism against the use of the oral antiretroviral drug tenofovir as a pre-exposure prophylaxis (PREP) for HIV/AIDS. Protests against trials of PREP; Concerns of the protestors; Threats to PREP trials.Item Knowledge and acceptability of HAART among TB patients in Durban, South Africa.(Taylor & Francis., 2005) Gebrekristos, Hirut T.; Lurie, Mark N.; Mthethwa, Nkosinathi.; Abdool Karim, Quarraisha.From October 2002 to February 2003, we conducted semi-structured interviews on knowledge of HIV, antiretroviral treatment, and willingness to participate in voluntary counselling and testing and HAART with 54 consenting patients attending a tuberculosis (TB) clinic in Durban, South Africa. 74% of patients interviewed reported not knowing anything about antiretroviral treatment (HAART). Knowledge of antiretroviral drugs (ARVs) was restricted to use in preventing mother to child HIV transmission (MTCT). 57.4% of the patients reported having an HIV test in the past, but less than 10% were aware of their current HIV status. Patients who did not know their current HIV status expressed fear and hesitation about testing HIV positive. However, 91% of the patients expressed willingness to participate in HIV treatment given the opportunity. The findings from this study indicate that knowledge of HIV treatment is limited. As access to HAART is expanded, information about HIV treatment options will need to be disseminated. TB centres may present unique opportunities for disseminating HIV prevention, care, and treatment options.Item A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope V3 sequences.(American Society for Microbiology., 2005) Jensen, Mark A.; Coetzer, Mia.; Van 't Wout, Angelique B.; Morris, Lynn.; Mullins, James I.In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5+ and 51 SI CXCR4+ sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.Item Scaling up HIV testing in resource-constrained settings: debates on the role of VCT and routine ‘opt-in or opt-out’ HIV testing.(South African Medical Association., 2005) Strode, Ann Elaine.; Van Rooyen, Heidi.; Heywood, Mark.; Abdool Karim, Quarraisha.Scaling up of the numbers of people voluntarily undergoing HIV testing has become vital, especially in resource-constrained settings, where the need for knowledge of HIV status for both prevention and care is critical. The reality is that for most people in Africa, access to HIV testing and to voluntary counselling and testing (VCT) has been very limited, and this has human rights implications – missing the opportunity to be diagnosed with a disease that is now well understood, manageable and treatable means certain death. The key challenge in our current context is how scaling up of HIV testing should be done. In responding to this challenge, we are guided by Gruskin and Loff,1 who state that ‘A human rights approach mandates that any public strategy, whether or not rights are to be restricted, be informed by evidence and widely debated. This approach protects against unproved and potentially counterproductive strategies, even those motivated by the genuine despair in the face of overwhelming public health challenges.’ This article describes the arguments and discussion raised during a session on models for increasing access to HIV testing at the 2nd National Conference on HIV/AIDS held in Durban in June 2005. It describes the legal framework for HIV testing in South Africa, frames the issues at the heart of the debate, and describes and discusses the various models of HIV testing, routine HIV testing, VCT and mandatory or compulsory HIV testing, within the context of HIV prevention and care. It concludes with recommendations.