High viral load and low CD4 cell count risk factors for non-HIV-related illnesses

Michael Carter
Published: 04 June 2009

Non-AIDS-defining illnesses are the most common cause of serious illness in French patients with HIV, according to a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Older age, a low CD4 cell count and continuing HIV replication were associated with the development of non-HIV-related illnesses.

“Our results give further arguments against interruption of combination antiretroviral therapy and underline the need to avoid virological rebound…particularly in older patients and/or those with a low CD4 cell count”, write the investigators.

Thanks to effective combination antiretroviral therapy, AIDS-defining illnesses are now rare in people with HIV. However, non-AIDS-related illnesses are becoming an increasingly significant cause of death in HIV-positive individuals.

Investigators from the French APROCO/COPILOTE (ANRS CO8) study undertook an analysis of causes of severe illness in 1231 patients who started a protease inhibitor-based antiretroviral regimen between 1997 and 1999.

Severe non-AIDS-defining illnesses were conditions leading to hospitalisation that were potentially life-threatening or caused death. Information was also gathered on serious side-effects related to antiretroviral therapy. These included lipodystrophy, increased blood lipids, symptomatic elevations in liver function, an allergic reaction to abacavir or nevirapine, anaemia caused by AZT, or kidney problems related to indinavir therapy. The investigators also recorded data on AIDS-defining events.

The patients were followed for a median of seven years and a total of 7664 person-years of follow-up were available for analysis. At the time HIV therapy was started the median CD4 cell count was 279 cells/mm3 and median viral load was 40,000 copies/ml.

In total, 801 severe non-AIDS-related events were recorded in 428 patients. The incidence of such events was 10.5 per 100 person years. There were 275 serious HIV treatment-related side-effects in 232 patients at an incidence rate of 3.6 per 100 person years. The total number of AIDS-defining illnesses was 126. These occurred in 126 patients at an incidence rate of 2.6 per 100 person years.

“The estimated probabilities of developing after seven years of follow-up a non-AIDS event, a combination antiretroviral-related event, and an AIDS-defining event were, respectively, 36%, 17%, and 8.5%”, comment the investigators.

A wide variety of non-AIDS-defining illnesses was observed in the patients. The most common were bacterial infections (23%), non-HIV-related cancers (10%), cardiovascular disease (10%), psychiatric disorders (9%) and neurological disease (6%). Despite 23% of the cohort being co-infected with hepatitis C virus, liver-related events were rare (2%). The investigators attribute this to the beneficial effects of antiretroviral therapy on the course of hepatitis C.

Next the investigators analysed the factors associated with the development of serious non-HIV-related illnesses.

These were age over 60 years (hazard ratio [HR], 2.1; 95% CI: 1.3-3.2); co-infection with hepatitis C virus (HR, 1.7; 95% CI: 1.4-2.1); a CD4 cell count below 100 cells/mm3 (HR, 2.5; 95% CI: 1.6-3.6); and a viral load above 10,000 copies/ml (HR, 1.9; 95% CI: 1.5-2.5).

A particularly strong association was observed between the development of non-AIDS-defining bacterial infections and viral load above 10,000 copies/ml, (adjusted HR [AOR], 2.48; 95% CI: 1.48-4.17, p < 0.001).

Age over 60 was significantly associated with the development of a non-AIDS-defining cancer (AOR, 2.03; 95% CI: 1.59-2.60, p < 0.001). There was a trend for a CD4 cell count above 500 cells/mm3 to be protective against the development of cancers (p = 0.06).

“Optimization and permanent continuation of long-term antiretroviral therapy in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity”, conclude the investigators.

Reference

Ferry T et al. Uncontrolled viral replication as a risk-factor for non-AIDS severe clinical events in HIV-infected patients on long-term antiretroviral therapy: APROCO/COPILOTE (ANRS CO8) cohort study. J Acquir Immune Defic Syndr (online edition), 2009.