title: Relationship between drug resistance mutations, plasma viremia, and CD4+ T-cell counts in patients with chronic HIV infection.
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.
authors.affiliation: Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Luz
authors.initials: L
authors.lastname: Martín-Carbonero
authors.forename: Oscar
authors.initials: O
authors.lastname: Gallego
authors.forename: Angélica
authors.initials: A
authors.lastname: Corral
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D015999:Multivariate Analysis; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D012194:RNA-Directed DNA Polymerase