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

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Abstract
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, 141–525) 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. J. Med. Virol. 76:1–6, 2005.
Funding Information
  • FIPSE
  • AIES
  • Fundación IES
  • FIS
  • RIS (Redes project 173)
  • CAM

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