The Survival Benefits of Antiretroviral Therapy in South Africa

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

HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10$54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At$150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV

Base case results of an analysis of hypothetical HIV cure strategies^*.

<p>*Based on assumptions for efficacy, durability, toxicity, and cost in Methods and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t001" target="_blank">Table 1</a>. Life expectancy, QALYs, and costs all discounted at 3%/year. <b>ART:</b> antiretroviral therapy; <b>QALY:</b> Quality-adjusted life year; <b>Dominated:</b> Less effective and more costly than the standard of care ART strategy.</p><p>Base case results of an analysis of hypothetical HIV cure strategies^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#nt103" target="_blank">*</a>}.</p

Stem Cell Transplantation compared to standard of care ART.

<p>The figure depicts the cost-effectiveness of Stem Cell Transplantation compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003" target="_blank">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). Instances where the intervention is both less expensive and less effective than ART are denoted in blue, but most were not cost-effective because the ICER of ART was <$100,000/QALY compared to SCT. The plus sign indicates a strategy that had an ICER for ART compared to SCT >$100,000/QALY gained. <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p

Chemotherapy compared to standard of care ART.

<p>The figure depicts the cost-effectiveness of Chemotherapy compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003" target="_blank">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p

Threshold which key parameters would need to reach for each type of HIV cure strategy to be cost-effective (ICER<$100,000/QALY gained) or cost-saving.

<p><b>ICER:</b> incremental cost-effectiveness ratio; <b>QALY:</b> quality-adjusted life year; <b>QOL:</b> quality of life; <b>Dominated:</b> strategy was less effective and more expensive than current ART.</p><p>*Cost reductions led to the strategy being less effective and less expensive than current ART. One could calculate an ICER for ART compared to Chemotherapy or Stem Cell Transplant, but it is not clinically plausible that these strategies would be used if they resulted in worse outcomes than standard of care with ART, even if they saved money by avoiding the costs of lifelong ART.</p><p>Threshold which key parameters would need to reach for each type of HIV cure strategy to be cost-effective (ICER<$100,000/QALY gained) or cost-saving.</p

Gene Therapy compared to standard of care ART.

<p>The figure depicts the cost-effectiveness of Gene Therapy compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003" target="_blank">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p

Parameter inputs for a model-based analysis of potential HIV cure strategies.

<p><b>SD:</b> standard deviation; <b>QOL:</b> quality-of-life.</p>a<p>Determined through initialization run of simulated cohort; ^bFor 24 months based on vorinostat; ^cFor monthly antiretroviral therapy, derived from weighted averages of current therapies until gene- or chemo-therapy is complete; ^dFor immunosuppressive agents, including methotrexate with tacrolimus.</p><p>Parameter inputs for a model-based analysis of potential HIV cure strategies.</p