Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy.
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.
Nicastri
Emanuele
E
National Institute of Infectious Diseases, IRCCS L. Spallanzani, Rome, Italy.
Sarmati
Loredana
L
d'Ettorre
Gabriella
G
Palmisano
Lucia
L
Parisi
Saverio G
SG
Uccella
Ilaria
I
Rianda
Alessia
A
Concia
Ercole
E
Vullo
Vincenzo
V
Vella
Stefano
S
Andreoni
Massimo
M
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
D019380:Anti-HIV Agents; D015684:Gene Products, pol; C060467:HIV pol protein p65; D054302:pol Gene Products, Human Immunodeficiency Virus