Small but higher rates of AIDS and non-AIDS complications with uncontrolled HIV despite CD4s over 350

EuroSIDA cohort members with a CD4 count above 350 and uncontrolled viral replication ran a higher risk of fatal and nonfatal AIDS than people with controlled viremia.

This 10,000-person analysis found less marked correlations between uncontrolled viremia at a 350-plus CD4 count and fatal or nonfatal non-AIDS complications usually heart disease, non-AIDS cancers, or liver disease.

The AIDS analysis involved 10,998 EuroSIDA cohort members, while the non-AIDS analysis involved 10,278. Everyone had a CD4 count above 350 and a viral load measured in one of three brackets: under 500, 500 to 10,000, or over 10,000. Inclusion began on 1 January 1997 for AIDS diagnoses and 1 January 2001 for non-AIDS diseases. The investigators halted follow-up if the CD4 count or viral load had not been measured in the preceding 6 months, if the CD4 count fell below 350, or at a persons last EuroSIDA visit or death.

During follow-up, the EuroSIDA team recorded 379 new AIDS diagnoses and 476 non-AIDS diagnoses. The most frequent non-AIDS problems were cardiovascular disease in 176, non-AIDS cancers in 163, and liver problems in 32. About 75% of cohort members were men, about 87% white, and about 45% infected through sex between men. More than 90% with a viral load under 500 copies/mL were taking antiretrovirals, compared with about 63% in the 500-to-10,000-copy bracket about 35% with a viral load above 10,000 copies/mL.

Incidence of new AIDS diagnoses was 2.38 per 100 person-years in people with a viral load above 10,000 copies/mL versus 0.69 per 100 person-years in those with a viral load under 500 copies/mL. This increased rate involved AIDS diagnoses of any severity. Incidence of non-AIDS diagnoses was similar in people with a viral load below 500 copies/mL (1.40 per 100 person-years), people with 500 to 10,000 copies/mL (1.56 per 100 person-years), and people with a load above 10,000 copies/mL (1.39 per 100 person-years). Rates of cardiovascular and non-AIDS cancer diagnoses were similar in the three viral load strata.

Multivariate analyses for AIDS diagnoses factored in viral load bracket, gender, HIV exposure group, region of European, HBV and HCV status, smoking status, hypertension, antiretroviral status, year of follow-up on antiretroviral therapy, and prior AIDS. This analysis determined that people with a viral load above 10,000 had a three times higher risk of a new AIDS diagnosis than those with a load under 500even though everyone had a CD4 count above
350.

The multivariate models for non-AIDS diagnoses adjusted for age, peak viral load, HIV exposure group, region of Europe, HBV and HCV status, diabetes, hypertension, smoking, prior AIDS, and antiretroviral status. Compared with cohort members who had a sub-500 viral load, those with 500 to 10,000 copies had a 48% higher rate of new non-AIDS diagnoses, while those with a load above 10,000 copies had a 54% higher rate. The impact of viral load on incidence of non-AIDS events was independent of CD4 count and similar in different CD4 strata.

The EuroSIDA investigators noted that they need a larger database to fully investigate the relationship between viral replication and specific non-AIDS events in patients who are not immune compromised.

Reekie J, Gatell J, Yust I, et al. Fatal and non-fatal AIDS and non-AIDS events in HIV-1 infected patients with high CD4 counts. 10th International Congress on Drug Therapy in HIV Infection. 711 November 2010. Glasgow. Abstract O342. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):O39. doi:10.1186/1758-2652-13-S4-O39. http://www.jiasociety.org/content/13/S4/O39