Most Patients with Highly Drug-resistant HIV Treated with an Incompletely Suppressive Regimen Maintain Durable Immunological and Virological Responses despite Acquiring New Resistant Mutations

Despite the recent approval of several new antiretroviral agents, some treatment-experienced patients with highly drug-resistant HIV have no option but to continue to receive an incompletely suppressive regimen.

Researchers at the University of Michigan Health System in Ann Arbor conducted a study to assess long-term immunological and virological responses to incompletely suppressive regimens, to investigate risks for immunological or virological failure, and to look for the occurrence of new drug-resistance mutations.

The investigators enrolled antiretroviral treatment-experienced HIV patients with a genotype sensitivity score </=1, an HIV viral load above1000 copies/mL, and no available optimized regimen.

They determined the proportion of patients treated with incompletely suppressive regimens who developed immunological failure (defined as a 25% reduction in CD4 cell count from the baseline level) and virological failure (defined as a 0.5-log10 or greater increase in the viral load from the baseline level).

Cox proportional hazards analysis was used to investigate variables associated with immunological or virological failure.

Results

• At baseline, 47 patients with 89 months median duration of prior antiretroviral therapy, a median CD4 cell count of 277 cells/mm3, and a median viral load of 19,728 copies/mL had multiple HIV mutations: a median of 5 nucleoside reverse-transcriptase inhibitor (NRTI) mutations, 1 non-nucleoside reverse-transcriptase inhibitor (NNRTI) mutation, and 6 protease inhibitor (PI) mutations.

• The median genotype sensitivity score at baseline was 0.

• After 48 months using an incompletely suppressive regimen, 43% experienced immunological failure and 22% experienced virological failure.

• New drug-resistance mutations were identified in 27 patients with sequential HIV genotypes available.

• New NRTI mutations occurred in 63.0% of patients, and new PI mutations occurred in 52.6% of protease inhibitor recipients.

• No deaths occurred.

• 8.5% of patients experienced a new AIDS-defining event.

• None of the studied variables were associated with immunological or virological failure, including age > 50 years, baseline HIV RNA > 100,000 copies/mL, baseline CD4 cell count < 200 cells/mm3, or inclusion of 3TC [Epivir] in the regimen.

Conclusion

Based on these results, the study authors concluded, "Most patients with highly drug-resistant HIV infection who were treated with an incompletely suppressive regimen maintain durable immunologic and virologic responses."

However, they added that, "New drug-resistant mutations occur frequently."

10/05/07

Reference
T Gandhi, V Nagappan, S Cinti, and others. Long-term immunologic and virologic responses in patients with highly resistant HIV infection who are treated with an incompletely suppressive antiretroviral regimen. Clinical Infectious Diseases 45(8): 1085-1092. October 15, 2007.