title: High prevalence of M184 mutation among patients with viroimmunologic discordant responses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis.
abstract: Whether highly active antiretroviral therapy (HAART) should be modified in patients with persistent increases in CD4(+) T cells despite detectable viral loads is an unresolved question. Forty-three heavily pretreated human immunodeficiency virus (HIV)-infected patients with virologic failure during HAART were studied before a change of therapy guided by genotypic analysis and during follow-up. Patients with an increase in CD4(+) cell count (>100 cells/ml) over pre-HAART values were considered to be discordant patients (20 individuals), whereas patients with a lower increase or no increase in CD4(+) cell count were considered failing patients (23 individuals). Based on univariate analysis, a high CD4(+) cell count before antiretroviral treatment, homosexual behavior as a risk factor for HIV infection, reduced drug exposure to nonnucleoside reverse transcriptase inhibitors, low replicative capacity of HIV isolates, and more frequent detection of HIV isolates with a non-B subtype, an R5 biological phenotype, and M184V and T215Y/F mutations were factors associated with a discordant response to HAART. Based on multivariate analysis, only the M184V mutation remained significantly associated with a viroimmunologic discordant response (odds ratio, 25.48; 95% confidence interval, 1.43 to 453.93). No difference in lamivudine exposure was found between discordant (95%) and failing (91%) patients. Twelve months after the genotypic analysis-guided change of therapy, 3 discordant (15%) and 6 failing patients (26%) achieved undetectable viral loads (<50 copies/ml), whereas in patients with HIV RNA loads of >500 copies/ml, discordant responses were observed in 5 out of 15 discordant patients and in 4 out of 16 failing patients. A relationship between the M184V mutation and a viroimmunologic discordant response to HAART was found. After the genotypic analysis-driven change of therapy, similar rates of virologic suppression were detected in the two groups.
authors.affiliation: Department of Public Health, University of Rome Tor Vergata, 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: Saverio G
authors.initials: SG
authors.lastname: Parisi
authors.forename: Lucia
authors.initials: L
authors.lastname: Palmisano
authors.forename: Clementina
authors.initials: C
authors.lastname: Galluzzo
authors.forename: Marco
authors.initials: M
authors.lastname: Montano
authors.forename: Ilaria
authors.initials: I
authors.lastname: Uccella
authors.forename: Roberta
authors.initials: R
authors.lastname: Amici
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Ercole
authors.initials: E
authors.lastname: Concia
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D009154:Mutation; D015995:Prevalence; D014779:Virus Replication
chemical_list: D054303:HIV Reverse Transcriptase; D016333:HIV Protease