ART-002

HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications.

HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2.

Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8).

Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.

Three-drug antiretroviral therapy (ART-3) has reduced complications and improved survival in HIV+ patients. The Chilean Public Health System began dual therapy (ART-2) in 1997, covering approximately 40% of patients in need.

To report the results of a follow-up of patients with and without access to ART in a Chilean public hospital.

Prospective follow-up of patients with ART-2 and 3 (cases) and patients with no access to ART (controls). All patients needed ART but it was available to a minority of them. Selection for ART was at random. Follow-up was between 6-24 months (11/96 to 3/99). Basal and periodic clinical and laboratory parameters were determined. Mortality and occurrence of new AIDS-defining events (ADE) were compared statistically using chi square.

One hundred and fifty cases (106 ART2, 28 ART3 and 16 ART2 expanded to ART3) and 166 controls were studied. Basal parameters were similar except prior ART (32.7 and 18.7% in cases and controls respectively). Close to 1/3 patients had AIDS. Cases had a mean follow up of 527 days; controls, 478. Six cases (4%) (5 in ART-2) and 17 controls (10%) died. Mortality x 100/pts/yr was 2.7 in cases and 7.7 in controls, p < 0.05. ADE per 100/pts/yr was 21 in cases (24.4 in ART2, 15.1 in TAR3) and 54.5 in controls, p < 0.05. Cases had a reduction of: esophageal candidiasis (84%), tuberculosis (75%), cryptococcosis and toxoplasmosis (66%), P carinii pneumonia (55%) and bacterial pneumonia (46%) and they had fewer hospitalizations (73%). Late assessment: 70 of 101 ART-2 patients had changed to ART-3 (1 death); 22 of 101 kept original ART-2 (12 dead, 10 alive), 39 of 43 ART-3 patients were alive and 1 died.

Short-term ART-2 and 3 significantly reduced mortality (60% and 73%) ADE (65% and 76% respectively) and hospitalizations. Benefits of ART-2 were short lived. Resource-constrained countries cannot depend on weaker than standard ART for proper care of people with HIV disease.