596b
When to Start ART—A Policy Evaluation While Awaiting Trial Results: South Africa
Rochelle Walensky*1,2,3, L Wolf2, R Wood4, M Fofana2, K Freedberg1,2,5,6, N Martinson7,8, D Paltiel9, X Anglaret10, M Weinstein5, and E Losina1,3,11,12
1Harvard Univ Ctr for AIDS Res, Harvard Med Sch, Boston, MA, US; 2Massachusetts Gen Hosp, Boston, US; 3Brigham and Women`s Hosp, Boston, MA, US; 4Desmond Tutu HIV Ctr, Inst of Infectious Diseases and Molecular Med, Univ of Cape Town, South Africa; 5Harvard Sch of Publ Hlth, Boston, MA, US; 6Boston Univ Sch of Publ Hlth, MA, US; 7Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 8Univ of the Witwatersrand, Johannesburg, South Africa; 9Yale Univ Sch of Med, New Haven, CT, US; 10Univ Victor Segalen Bordeaux 2, France; 11Massachusetts Gen Hosp, Boston, US; and 12Boston Univ Sch of Publ Hlth, MA, US
Background: Results of international clinical trials
assessing when to initiate ART will not be available for several years. Our
objective was to inform South African HIV treatment decisions regarding the
optimal CD4 threshold for ART initiation while awaiting trial results.
Methods: We used a published mathematical model of
HIV-infection in South Africa to simulate 3 alternative ART initiation
strategies: No ART (for comparison only); ART at CD4 <250/μL or severe
opportunistic disease (OD); and ART at CD4 <350/μL or severe OD. All
strategies include co-trimoxazole prophylaxis. We projected 5-year morbidity,
mortality, and costs, in a South African cohort of HIV-infected persons with
mean age 33 years under each ART initiation strategy. Natural history and
healthcare utilization data were derived from the Cape Town AIDS Cohort. We
assumed 2 sequential ART regimens (NNRTI-based followed by PI-based), with
published 48-week viral suppression rates of 84% and 71%, and per person annual
costs of $288 and $564. We developed a decision criterion for ART at
<350/μL now, while awaiting trial results. The criterion is based on:
the subjective probability that the trial will demonstrate a benefit to ART at
<350/μL, and a cost-effectiveness threshold ≤$16,200 per year of
life saved (≤3 times the South African per capita GDP).
Results: Over a 5-year horizon, we project that 4.7
million HIV+ South Africans will become eligible to start ART in the
CD4 250 to 350/μL treatment window. Assuming all eligible patients present
for care and that ART is equally effective in the CD4 250 to 350/μL range,
initiation of ART at <350/μL compared to <250/μL would result
in fewer total OD (730,272 vs 951,370) and fewer total deaths (244,249 vs
497,059). Starting at <350/μL would also lead to additional
(discounted) treatment costs of $1.4 billion over the next 5 years. If fewer
patients are identified, fewer deaths and OD are averted, and ART costs are
reduced. As long as the probability that the trial will confirm a survival
benefit to earlier ART is judged to be greater than 17%, a policy of initiating
ART at CD4 <350/μL is cost-effective and should be used over the next 5
years.
Conclusions: Earlier ART initiation in South Africa will reduce morbidity and mortality substantially, and will be cost-effective.
In anticipation of trial results, treatment guidelines should be liberalized to
allow for earlier ART initiation (CD4<350/μL).
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