Scaling Up Antiretroviral Therapy in South Africa: The Impact of Speed on Survival

The Divisions of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 06/2008; 197(9):1324-32. DOI: 10.1086/587184
Source: PubMed


Only 33% of eligible human immunodeficiency virus (HIV)-infected patients in South Africa receive antiretroviral therapy (ART). We sought to estimate the impact of alternative ART scale-up scenarios on patient outcomes from 2007-2012.
Using a simulation model of HIV infection with South African data, we projected HIV-associated mortality with and without effective ART for an adult cohort in need of therapy (2007) and for adults who became eligible for treatment (2008-2012). We compared 5 scale-up scenarios: (1) zero growth, with a total of 100,000 new treatment slots; (2) constant growth, with 600,000; (3) moderate growth, with 2.1 million; (4) rapid growth, with 2.4 million); and (5) full capacity, with 3.2 million.
Our projections showed that by 2011, the rapid growth scenario fully met the South African need for ART; by 2012, the moderate scenario met 97% of the need, but the zero and constant growth scenarios met only 28% and 52% of the need, respectively. The latter scenarios resulted in 364,000 and 831,000 people alive and on ART in 2012. From 2007 to 2012, cumulative deaths in South Africa ranged from 2.5 million under the zero growth scenario to 1.2 million under the rapid growth scenario.
Alternative ART scale-up scenarios in South Africa will lead to differences in the death rate that amount to more than 1.2 million deaths by 2012. More rapid scale-up remains critically important.

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    • "Second, as case detection increases, larger numbers of HIV-infected persons will be identified before they are eligible for ART, and so it will become increasingly important to track and monitor these persons until they are eligible for ART. Furthermore, our sensitivity analyses illustrate that the rate at which untreated eligible patients are linked to care drives survival benefits, demonstrating the impact of speed of scale-up on survival [13]. Base-case survival benefits as of 2030 range from 17.9 million life-years without linkage to care of any additional patients to 29.4 million life-years with immediate linkage to care of 84% of untreated patients eligible for ART each year. "
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    ABSTRACT: Background: We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)-infected patients initiating ART each year during 2004-2011. Model inputs included cohort-specific mean CD4(+) T-cell count at ART initiation (112-178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%-71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results: Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004-2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions: We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa.
    The Journal of Infectious Diseases 12/2013; 209(4). DOI:10.1093/infdis/jit584 · 6.00 Impact Factor
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    • "Therefore the results from this analysis have important policy implications that are relevant to other resource-limited settings. The rapid expansion of access to ART in resource-limited settings is both needed [29] and challenging [30]. Our findings suggest that managed private-care for public sector patients could be used to increase access to ART, provided that the private practices follow national protocols and that loss to follow-up is managed – key components of the private-care program in our study. "
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    ABSTRACT: Providing private antiretroviral therapy (ART) care for public sector patients could increase access to ART in low- and middle-income countries. We compared the costs and outcomes of a private-care and a public-care ART program in South Africa. A novel Markov model was developed from the public-care program. Patients were first tunneled for 6 months in their baseline CD4 category before being distributed into a dynamic CD4 and viral load model. Patients were allowed to return to ART care from loss to follow up (LTFU). We then populated this modeling framework with estimates derived from the private-care program to externally validate the model. Baseline characteristics were similar in the two programs. Clinic visit utilization was higher and death rates were lower in the first few years on ART in the public-care program. After 10 years on ART we estimated the following outcomes in the public-care and private-care programs respectively: viral load <1000 copies/ml 89% and 84%, CD4 >500 cells/μl 33% and 37%, LTFU 14% and 14%, and death 27% and 32%. Lifetime undiscounted survival estimates were 14.1 (95%CI 13.2-14.9) and (95%CI 12.7-14.5) years with costs of 18,734 (95%CI 12,588-14,022) and 13,062 (95%CI 12,077-14,047) USD in the private-care and public-care programs respectively. When clinic visit utilization in the public-care program was reduced by two thirds after the initial 6 months on ART, which is similar to their current practice, the costs were comparable between the programs. Using a novel Markov model, we determined that the private-care program had similar outcomes but lower costs than the public-care program, largely due to lower visit frequencies. These findings have important implications for increasing and sustaining coverage of patients in need of ART care in resource-limited settings.
    PLoS ONE 02/2013; 8(2):e53570. DOI:10.1371/journal.pone.0053570 · 3.23 Impact Factor
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    • "Noteworthy, the study participants were started on ART at CD4 counts < 250 cells/μl. This is clearly severe immune suppression considering the growing evidence initiation of ART at higher CD4 counts yields better clinical and immunological outcomes [25,26]. This study adds evidence to the current evidence that early initiation of ART not only increases CD4 counts and survival [6,25-27], but also lowers the levels of T-cell activation and possibly improves T-cell function recovery. "
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    ABSTRACT: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
    BMC Infectious Diseases 02/2011; 11(1):43. DOI:10.1186/1471-2334-11-43 · 2.61 Impact Factor
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