Starting HIV treatment early, when CD4 cell counts fell below 350 cells/mm3 in accordance with current World Health Organization (WHO) recommendations, was cost-effective compared to starting at 200 cells/mm3 (standard ART) over a three-year period in Haiti, American and Haitian researchers report in the September 11 edition of PLoS Medicine.
Haiti is one of the world’s poorest countries, lying in the bottom 10% of countries by GDP per capita in 2010. It is the poorest nation in the western hemisphere.
Serena P Koenig and colleagues did a cost-effectiveness study of early compared to standard ART using data from a prospective randomised trial (CIPRA HT-001). The trial was undertaken in 2009 at the Center of the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO) among HIV-infected patients with a CD4 cell count between 200 and 350 cells/mm3.
The trial showed early ART compared to standard ART reduced death rates by 75% after a median follow-up of 21 months.
After three years the total cost of saving one life by starting ART early rather than waiting until the CD4 cell count was under 200 cells/mm3 was US$2,050 with research-related costs excluded (95% CI: US$722/YLS-US$5,537/YLS).
WHO’s formula for the cost-effectiveness of a medical intervention is defined as less than three times a country’s gross domestic product (GDP) for each person for each disability-adjusted life year saved (DALY) and very cost-effective if under one times the GDP.
The authors used years of life saved (YLS) rather than DALY and note YLS is generally acceptable in this formula. The threshold in Haiti in 2009 was US$2,355/YLS. The GDP for each person in Haiti is US$785.
In November 2009 based on the results of the CIPRA HT-001 trial together with a post hoc analysis within the SMART trial WHO changed its guidelines for starting ART to when CD4 cell counts fell below 350 cells/mm3 rather than 200 cells/mm3. The panel responsible for the recommendations “placed a high value on avoiding death, disease progression and HIV transmission over and above cost and feasibility.”
At the end of 2009 in low- and middle-income countries an estimated 14.5 million were in need of ART yet only 5.3 million were getting it; and in Haiti, with an estimated prevalence of 2.2%, an estimated 43% (26,000) of people with CD4 cell counts below 350 cells/mm3 were on ART.
Policy makers in low- and middle-income countries have to make difficult decisions in how to allocate and make the best use of limited resources.
Putting the guidelines into practice will be determined in large part by knowing whether it is cost-effective.
The authors, in what they believe to be the first analysis of its kind, compared the costs and survival benefits of early to standard ART using data from a randomised clinical trial (CIPRA HT-001) that compared these two strategies in HIV-infected adults with no history of an AIDS-defining illness and a CD4 cell count between 200 and 350 cells/mm3.
Data included: use and costs of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures and hospital services.
Among 816 participants enrolled between 2005 and 2008, the authors determined cost for each year of life saved including patient and caregiver costs, with a median of 21 months and a maximum of three years of follow-up.
During the trial mean total costs for each patient in the early arm were US$1,381 and US$1,033 for standard ART. When research-related costs were excluded and clinical benefit not taken into account, the costs were US$1,158 and US$979, respectively.
While early ART had higher mean ART costs (US$398 compared to US$81), those in the standard arm had higher costs for HIV physician visits, other medications, CD4 cell counts, clinically indicated laboratory tests and radiographs (US$275 compared to US$384).
The authors note that HIV treatment protocols, laboratory tests and medications costs are similar to those used in other resource-poor settings, and in particular those funded in part by PEPFAR. Their findings, they argue, can be generalised to non-trial settings since medical services including nurse and physician contact were comparable at GHESKIO.
The authors note that the cost-effective ratios are conservative and biased against early ART; the clinical benefits of early ART that extend beyond the three years are not taken into account.
Baseline median CD4 cell counts for the early arm compared to the standard arm at the start of ART were 280 cells/mm3 and 166 cells/mm3, respectively.
Studies have shown higher baseline CD4 counts are associated with better immunological recovery and lower mortality and conversely baseline counts under 200 are linked to higher rates of death and disease, including tuberculosis.
The authors note their findings are comparable to results from computer-simulation models in South Africa and Morocco.
The authors conclude starting ART “in HIV-infected adults with CD4 counts between 200 and 350 cells/mm3 in Haiti is cost-effective after excluding laboratory monitoring and clinical benefit. Financial and operational resources should be prioritised so that resource poor countries [can put the new WHO guidelines into practice].”
Koenig SP et al. Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti. PLoS Med 8(9): e1001095. doi: 10.1371/journal.pmed.1001095, September 2011.