Public Health

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Challenges in the integration of TB and HIV care : evidence for improving patient management and health care policy.
(2016) Naidoo, Kogieleum.; Abdool Karim, Salim Safurdeen.
TB infection remains a leading cause of morbidity and mortality among patients with HIV infection, while HIV is the strongest risk factor for development of active TB. Integration of HIV and TB treatment is key to reducing mortality in co-infected patients; but many obstacles stand in the way of effective scale-up of this approach to HIV-TB treatment. The challenges associated with HIV-TB integration extend from clinical complexities in individual patient management, to impediments in health service organization and prioritization to address this urgent public health priority, especially in sub-Saharan Africa where TB-HIV co-infection rates reach 80%. The purpose of this study was to assess and identify strategies to overcome the challenges in immune reconstitution and drug safety/tolerability when integrating HIV and TB care in a cost-effective manner to reduce co-infection mortality. Clinical and operational service data from the Starting Antiretroviral therapy at three Points in Tuberculosis Treatment (SAPiT – CAPRISA 003) study, a 3-arm, randomized control trial in 642 newly diagnosed sputum smear-positive TB-HIV co-infected adult patients with screening CD4+ cell count < 500 cells/mm3, were analysed. In addition, the incidence rate of unmasked clinical TB following ART initiation was assessed through a retrospective chart review conducted in HIV infected patients enrolled at the rural CAPRISA AIDS Treatment Programme. Overall, mortality was 56% lower (RR=0.44; 95% CI: 0.25 to 0.79; P = 0.003) in patients initiated on ART during TB treatment compared to ART deferral to after TB treatment completion. However, the risk of immune reconstitution inflammatory syndrome (IRIS) was higher (incidence rate ratio (IRR), 2.6 (95% CI, 1.5 to 4.8); P < 0.001, in patients initiating ART within the first 2 months compared to later ART initiation during TB treatment. In the most severely immuno-compromised patients (CD4 counts <50 cells/mm3) early ART integration was associated with an almost five-fold increased risk of IRIS (IRR 4.7 (95% CI, 1.5 to 19.6); P = 0.004. Patients initiating ART in the first 2 months of TB therapy had higher hospitalization rates (42% vs. 14%; P = 0.007) and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) than patients in the other two groups. When assessing available evidence, these results indicate that ART initiation in patients with CD4 cell counts >50 cells/mm3 would be most appropriate after completion of intensive phase of TB therapy, a strategy that was found to cost $1840 per patient treated. Among HIV infected patients initially screening negative for TB there was a fourfold higher incidence rate of unmasking TB in the first 3 months after ART initiation, compared to the subsequent 21 months post-ART initiation. The new information generated by this study provides important evidence for policy and clinical management of patients with HIV and TB co-infection. Firstly, careful clinical vigilance for ‘unmasked’ TB is required in patients initiating ART. Secondly, the survival benefit of AIDS therapy in TB patients can be maximized by initiating ART as soon as possible after TB therapy has been started in patients with advanced immunosuppression, i.e., those with CD4+ counts <50 cells/mm3. However, patients with higher CD4+ cell counts should delay ART initiation to at least 8 weeks after the start of TB therapy to minimize the incidence and duration of immune reconstitution disease and consequent hospitalization. Thirdly, this approach, which is at variance with current World Health Organization policy and guidelines, is cost-effective and readily implementable within the clinical setting. Finally, addressing the operational challenges to HIV-TB treatment integration can improve patient outcomes with substantial public health by reducing mortality by the most important causes of death in South Africa.
Incidence of HIV infection in rural KwaZulu-Natal in the context of the epidemiology and impact of HIV/AIDS in South Africa.
(2007) Gouws, Eleanor.; Abdool Karim, Salim Safurdeen.; Jinabhai, Champaklal Chhaganlal.
South Africa has had one of the fastest growing HIV epidemics in the world and almost 30% of women attending public antenatal clinics (ANC) are currently infected with the virus. But as the epidemic is starting to level off and antiretroviral therapy (ART) is becoming increasingly available, few methods exist to determine the impact of ART or other interventions on the epidemic in South Africa. This thesis explores the epidemiology and dynamics of HIV infection and investigates the potential impact of ART. Methods Total and age-specific prevalence data are analysed in time and space and are used to investigate patterns of infection in men and women, urban and rural, and low and high risk populations. Dynamical models are developed to estimate incidence from age-specific prevalence and trends over time and are compared to laboratory-based estimates of recent HIV sero-conversion. Incidence is estimated in different populations in South Africa. A dynamical model is developed to estimate the impact of ART on the future course of the HIV epidemic. Results HIV prevalence varies geographically and by age, sex and race. The average female-tomale HIV prevalence ratio is 1.7 and prevalence peaks at an older age among men than women. The age at which prevalence peaks among women has increased from 23.0 to 26.5 years between 1995 and 2002. Four patterns of infection are identified: among pregnant women attending ANCs, among men and women in the general population, and among migrant workers. HIV incidence among ANC attendees peaked in the mid to late 1990s (at 6.6% per year nationally) with variation between provinces. Current estimates of HIV prevalence and incidence among the general population in South Africa (aged 15-49 year) are 18.8% and 2.4% per year, respectively. Age-specific incidence estimates from dynamical models and laboratory methods are in good agreement provided the window period for the laboratory method is increased. Over the next ten years the provision of ART could avert 1 to 1.5 million deaths depending on whether it is provided when the CD4 cell count falls to 200 or 350 cells/ul. By 2015 about 1.1 million people will be receiving ART but this will have little impact on the incidence of HIV and scaling up of prevention efforts remains urgent. Conclusions The thesis explores some of the determinants and patterns of HIV prevalence and incidence in South Africa in order to find better ways to manage the epidemic of HIV, monitor changes and evaluate progress in control efforts. In order to fight the epidemic we need to mobilize the best possible science in support of those people and communities affected by the epidemic.
Predictors of HIV acquisition in high risk women in Durban, South Africa.
(2015) Naicker, Nivashnee.; Kharsany, Ayesha Bibi Mahomed.; Abdool Karim, Salim Safurdeen.
In South Africa young women bear a disproportionate burden of HIV infection however, risk factors for HIV acquisition are not fully understood in this setting. In a cohort of 245 HIV negative women, we used proportional hazard regression analysis to examine the association of demographic, clinical and behavioural characteristics with HIV acquisition. The overall HIV incidence rate (IR) was 7.20 per 100 women years (wy), 95% Confidence Interval (CI) 4.20–9.80]. Women 18 to 24 years had the highest HIV incidence [IR 13.20 per 100 wy, 95% CI 6.59–23.62] and were almost three times more likely to acquire HIV compared to women 25 years and older [adjusted Hazard Ratio (aHR) 2.61, 95% CI 1.05–6.47]. Similarly, women in relationships with multiple sex partners [IR 8.97 per 100 wy, 95% CI 5.40–14.0] had more than twice the risk of acquiring HIV when compared to women who had no partner or who had a husband or stable partner (aHR 2.47, 95% CI 0.98–6.26). HIV prevention programmes must address young women’s vulnerability and promote safer sex practices for high risk women.

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