15% of patients who fail treatment with NRTI, NNRTIs and PIs die within 3 years

Approximately 15% of HIV-positive patients who have failed to achieve sustained virological suppression after receiving treatment with drugs from all the three main classes of anti-HIV medicines will die within three years. CD4 cell count and stopping anti-HIV treatment are the strongest predictors of death, according to data from the PLATO (Pursuing Later Treament Options) study presented to the 43^rd Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago on Sunday 14^th September.

The PLATO study involved 2,488 patients with resistance to NRTIs, NNRTIs and protease inhibitors from 13 different cohorts. Patients were eligible for inclusion in the study if they had an HIV viral load above 1,000 copies/mL for four months whilst receiving treatment with NRTIs, NNRTIs and protease inhibitors either in combination or sequentially.

Investigators calculated the rate of death and factors predicting mortality.

A total of 5,015 patient years of follow-up were contributed to the study, and 276 deaths were recorded, meaning that the mortality rate was 5.5 per 100 person years of follow-up and the three year predicted mortality rate was 15%.

The median CD4 cell count taken closest to death was 16 cells/mm³ (range 6 - 60 cells/mm³), a count which is indicative of very advanced immune damage.

Cause of death was known for 76% of patients, and of these 66% died due to an HIV-related cause.

A CD4 cell count below 50 cells/mm³ was the strongest predictor of death (Hazard Ratio (HR) 15.8, 95% CI, 9.3 - 27.00). Conversely, no relationship was found between the last HIV viral load taken before death and the risk of mortality.

The investigators did, however, find that there were several other factors which significantly increased the risk of death. These included not taking anti-HIV therapy (HR 2.85, 95% CI, 1.98 - 4.10), a prior AIDS-defining illness (HR 1.53, 95% CI, 1.11 - 2.10), age (HR 1.24 for every additional ten years, 95% CI, , 1.06 - 1.44), and injecting drug use (HR 1.65, 95% CI, 1.05 - 2.54).

There is a high risk of death in patients who have experienced treatment failure to all the three man classes of anti-HIV therapy, conclude the investigators, the risk being highest for patients who stop taking anti-HIV drugs and/or have severe immune damage. The primary aim of anti-HIV therapy in patients with extensive treatment experience should, the investigators recommend, be the maintenance of a CD4 cell count of at least 200 cells/mm³. In addition, the investigators stress that HAART should only be interrupted with great care in highly treatment-experienced patients.