The first five years of a large-scale antiretroviral programme have resulted in excellent, sustained rates of virologic suppression, CD4 cell count increases, and improved clinical outcomes among adults in Botswana, according to a study reported in AIDS.
The Botswana Antiretroviral Treatment Program (commonly known as MASA, from the Setswana word for "new dawn") began providing free access to antiretroviral therapy (ART) in January 2002 through Princess Marina Hospital in the capital city of Gaborone. The programme has since expanded dramatically, currently serving over 90,000 HIV-positive persons through 32 care sites. Large-scale data from Botswana were presented earlier this year at the Seventeenth International AIDS Conference in Mexico City. This published report presents outcomes from the first 633 patients to receive ART through the original programme site at Princess Marina Hospital (PMH).
Between January and August 2002, 871 HIV-positive adults were registered at the PMH site, of whom 633 were started on ART within two weeks of registration. (The remainder were already receiving treatment through the private sector, were not yet eligible, were lost to follow-up or died before treatment could be started.) These 633 patients had extremely advanced HIV disease, with a median CD4 cell count of 67 cells/mm3, median HIV viral load of 444,000 copies/ml, 81% at WHO disease stage 3 or 4, and widespread active or recent opportunistic infections. Median age was 35 years and 60% were women.
The participants began non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination ART and followed for a median of 41.9 months. The most common first-line regimens were coformulated AZT/3TC plus either efavirenz (50.6%) or nevirapine (44.4%); patients with significant anaemia were offered stavudine (d4T) instead of AZT.
Outcomes were described after one year (n=373), three years (n=294), and five years (n=100). During follow-up, 120 of the 633 patients died. Mortality rates were highest during the first year of treatment, with 86% of all deaths occurring within the first year, and 50% within the first three months. The Kaplan–Meier survival estimates at one, three, and five years were 82.7% (95% confidence interval [CI], 81.2–84.3%), 79.3% (95% CI, 77.6–81.0%), and 79.0% (95% CI, 77.3–80.7%), respectively. The most common causes of death were advanced AIDS-related conditions, not drug toxicities. Not surprisingly, the most significant factors associated with death were baseline CD4 cell counts below 50 cells/mm3 (p=.0001), WHO clinical stage 3 or 4 (p=.003), and baseline haemoglobin below 8.0 g/dl (p=.0087).
Most surviving patients quickly achieved and maintained stable virologic suppression: after one, three, and five years, the percentages of patients with a viral load less than 400 copies/ml were 91.3%, 90.1%, and 98.3%, respectively. The risk of virologic failure or death at one, three and five years was 17.6% (95% CI, 16.0–19.1%), 22.1% (95% CI, 20.3–23.8%) and 30.1% (95% CI, 28.0–32.2%), respectively; a total of 47 patients experienced virologic failure during follow-up.
Significant, continuing increases were seen in CD4 cell counts: the median CD4 cell count increases after one, three, and five years were 169, 302, and 337 cells/mm3, respectively. Larger increases were seen in those who started ART with baseline CD4 cell counts less than 50 cells/mm3 (162, 298, and 326 cells/mm3 at one, three, and five years). By four years of treatment, there were no significant differences in absolute CD cell counts between those who began treatment above or below 50 cells/mm3.
During the first six months, serious, potentially life-threatening events included anaemia, skin reactions (drug hypersensitivity), and liver toxicity. At six months, the risk of treatment modification due to anaemia was 6.94% (95% CI, 5.9–8.0%), for hypersensitivity reactions, 1.3% (0.8–1.7%), and for hepatotoxicity, 1.1% (0.7–1.6%).
Adherence was measured only by monthly medication refills, beginning in July 2002 when a computerised pharmacy record system was introduced. Adherence was high by that measure, with a mean overall monthly refill rate of 92.5% (95% CI, 91.2–93.6%).
The authors concluded that the "vast majority of ART-treated adults exhibited excellent immune recovery" in this severely immune-compromised cohort – results that are similar to those seen in other populations with advanced disease. These outcomes represent "one of the longest follow-up time periods of any public ART programme[s] in Africa." While the high rates of sustained suppression and adherence were very encouraging, the high early mortality rates were a great concern and "highlight the importance of earlier ART initiation".
Reference:
Bussmann H et al. Five-year outcomes of initial patients treated in Botswana's National Antiretroviral Treatment Program.AIDS 22:2301–2311, 2008.