title: Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy.
abstract: The fitness of human immunodeficiency virus (HIV) in vivo depends on the interaction of a multitude of viral and host factors. The aim of this study was to analyze the biological phenotype and the intrinsic capacity of the HIV isolates with drug-resistance mutations to replicate efficiently in the absence of drugs. An open label multicenter cross-sectional study was undertaken on 28 HIV-infected patients failing antiretroviral treatment. The subjects were studied for CD4+ cell count, HIV viral load, syncytium-inducing phenotype, genotypic drug-resistance assay, and replication capacity of HIV isolates assessed by co-culture assay. All HIV isolates showed a decreased replication capacity compared with wild-type strains. The lowest replication capacity was detected in HIV strains with more than five drug-resistance mutations. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. Isolates with R5 biological phenotype had a higher number of resistant mutations than X4 isolates (P = 0.004). Particularly, the R5 phenotype was detected in all 6 isolates with more than 14 drug-resistance mutations. Patients with R5 strains had plasma viral load similar to patients with X4 strains, but marginally higher CD4+ cell counts, and their HIV isolates had significantly lower replication capacity of HIV isolates (P = 0.008). No patient carrying HIV with a maintained replication capacity had a viral load less than 30,000 copies/ml. In patients failing HAART, the detection of HIV isolates with the R5 biological phenotype correlates with CD4+ cell count, an impaired replication capacity, and a high number of drug-resistance mutations.
authors.affiliation: National Institute of Infectious Diseases, IRCCS L. Spallanzani, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastri
authors.forename: Loredana
authors.initials: L
authors.lastname: Sarmati
authors.forename: Gabriella
authors.initials: G
authors.lastname: d'Ettorre
authors.forename: Lucia
authors.initials: L
authors.lastname: Palmisano
authors.forename: Saverio G
authors.initials: SG
authors.lastname: Parisi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Uccella
authors.forename: Alessia
authors.initials: A
authors.lastname: Rianda
authors.forename: Ercole
authors.initials: E
authors.lastname: Concia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015684:Gene Products, pol; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication; D054302:pol Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015684:Gene Products, pol; C060467:HIV pol protein p65; D054302:pol Gene Products, Human Immunodeficiency Virus