Relationship between drug resistance mutations, plasma viremia, and CD4+ T-cell counts in patients with chronic HIV infection

Transmission of drug-resistant viruses has been shown to be associated with lower virus replication capacity and higher CD4(+) cell counts in recent human immunodeficiency virus (HIV) seroconvertors. The impact of drug resistance mutations on CD4 cell counts in chronically HIV-infected patients has not been examined. A total of 825 patients whose plasma specimens were submitted to a reference laboratory for genotypic testing from 1999 to 2002 were analyzed. There was no significant difference in the median CD4(+) cell count when comparing 63 drug-naive and 762 treatment-experienced patients [399 (IQR, 141525) vs. 319 (IQR, 174-521); P = 0.8]. In contrast, the median viral load was significantly higher in drug-naive than in pre-treated patients [4.6 (IQR, 4.1-5.25) vs. 4.1 (IQR, 3.4-4.7) logs; P < 0.0001]. Overall, drug resistance mutations appeared in 81% of patients, with a median number of 9 (IQR, 5-14). The rate of drug resistance genotypes was 9.5% for drug-naive patients and 86.7% for pre-treated individuals. In the univariate analysis, a lower viral load (P < 0.0001), the presence of drug-resistant viruses (P = 0.038), and specific mutations in the reverse transcriptase (RT) gene [presence of M184V (P = 0.016) or K70R (P < 0.0001), and lack of L74V (P < 0.003)] were all associated with higher CD4(+) counts. However, in the multivariate analyses, only a lower viral load and the presence of K70R were significantly associated with higher CD4(+) cell counts. In summary, drug-resistant viruses are associated with lower viral loads, but after adjusting for plasma viremia, subjects carrying drug-resistant viruses do not show significantly higher CD4 cell counts. Thus, keeping on treatment HIV-infected individuals failing virologically and harboring drug-resistant viruses may ameliorate their immunological deterioration until new drugs became available. (c) 2005 Wiley-Liss, Inc.