436   Clinical Impact of Baseline Genotypic Resistance.

S. A. Tasker*¹, S. K. Brodine², S. A. Wegner¹, N. E. Aronson³, A. J. Barile⁴, K. T. Stephan⁵, M. R. Wallace⁶, C. Tamminga⁷, J. Wesner², B. Larder⁸, and J. R. Mascola⁹.
¹US Military HIV Res. Program, Rockville, MD;²San Diego State Univ., CA;³Walter Reed Army Med. Ctr., Washington, DC;⁴Natl. Naval Med. Ctr., Bethesda, MD;⁵Wilford Hall Air Force Med. Ctr., San Antonio, TX;⁶Naval Med. Ctr., San Diego, CA;⁷Naval Med. Ctr., Portsmouth, VA;⁸Virco-UK, Cambridge ; and⁹Vaccine Res. Ctr., NIH, Bethesda, MD.

Background:The clinical significance of antiretroviral drug resistance mutations present prior to the initiation of therapy is unknown. The US military tests all active-duty personnel for HIV infection every 1—3 years. Since 1997 the majority of newly identified seroconverters have enrolled in a study that includes baseline resistance testing via genotype and phenotype (Virco-UK). Initial therapy was begun without knowledge of the resistance assay results.

Methods:We evaluated all enrolled patients who had a baseline drug-naïve blood sample and at least 6 months follow-up with CD4 count and HIV RNA PCR (n = 103).

Results:Twenty-one patients had intermediate or resistant virus according to Vircogen-I interpretation (group R). Baseline mean CD4 cells/mm³and log₁₀plasma HIV RNA were similar in both groups (CD4: R = 498, S = 463; log₁₀HIV RNA: R = 4.7, S = 4.5), but at six months the R group had greater increases in CD4 cells/mm³(R = +230, S = +122; p < 0.05) and greater decreases in log₁₀HIV RNA (R = -3.0, S = -2.1; p < 0.02). There were no significant differences in antiretroviral therapy, including protease inhibitor or nonnucleoside reverse transcriptase inhibitor use, between the two groups. Of those patients on at least 3 antiretroviral drugs, the changes in CD4 cells/mm³were R = +269 (n = 17), S = +170 (n = 63), p < 0.05, and changes in log₁₀HIV RNA were R = -3.2, S = -2.7, p = 0.14. Patients with primary resistance mutations (n = 8) on 3-drug therapy had mean +332 cell increase (p = 0.02 vs S group) and mean -3.4 log₁₀HIV RNA decrease (p = 0.19 vs S group) at six months.

Conclusions:Patients in this cohort with genotypic resistance mutations present at baseline had greater CD4 cell increases and log₁₀HIV RNA decreases in the first 6 months of follow-up compared to those with wild-type HIV infection. This suggests that mutations conferring resistance may either decrease viral fitness or cause hypersensitivity to other antiretroviral drugs.