Relationship between drug resistance and HIV-1 disease progression or death in patients undergoing resistance testing

To evaluate factors associated with drug resistance detected by genotypic antiretroviral resistance testing (GART), and to determine the association between the level of resistance and subsequent human immunodeficiency type 1 (HIV-1) disease progression or death.

Observational cohort study.

We identified highly active antiretroviral therapy (HAART)-treated patients who had GART as part of clinical management. Factors associated with greater numbers of resistance mutations were assessed by ordinal logistic regression. Survival analysis was used to assess time to a new opportunistic condition or death following GART.

A total of 572 patients were identified who had GART: of these, 50% had 0-2 resistance mutations, 33% had 3-6 mutations, and 17% had >/= 7 mutations. In multivariate analysis, prolonged use of HAART in the setting of incomplete viral suppression was significantly associated with more drug resistance. Patients with fewer resistance mutations were significantly more likely to achieve viral suppression after GART than patients with more mutations. Compared to patients with two or less resistance mutations, those with three to six mutations, or seven or more mutations were not at higher risk of HIV-1 disease progression or death over a median follow-up of 15 months. In contrast, continued HAART use following GART was strongly associated with slower disease progression, particularly at lower CD4 cell counts.

These results support the hypothesis the drug-resistant HIV-1 may be less pathogenic than wild-type virus, and that continued use of HAART might provide clinical benefit, despite persistent viremia and HIV-1 drug resistance.