Plasma HIV RNA decline and emergence of drug resistance mutations among patients with multiple virologic failures receiving resistance testing-guided HAART.
Early recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted. The rate of PVL decline was studied by weekly PVL determinations. To assess DRM accumulation, serial GRTs were performed in all nonresponders (never reaching PVL <50 or two PVLs >50 copies/ml after suppression). Over 48 weeks, 10 patients (26%) were nonresponders. Receiving less then two fully active drugs and having an elevated number of PI and NRTI mutations at baseline were strongly associated with virologic failure. There was no evidence of a difference in the change from baseline PVL to week 1 and 2 between responders and nonresponders. By contrast, PVL reductions from week 2 to week 3 and thereafter were significantly greater for responders (p < 0.01). Among nonresponders, the incidence rates per patient-month (95% CI) of emergent DRM were 0.67 (0.13-1.20), 0.40 (0.00-0.74), and 0.37 (0.00-0.75) at weeks 4, 8, and 24, respectively. Having limited baseline resistance, receiving at least two fully active drugs, and showing constant PVL reductions from week 2 to week 3 and thereafter were predictive of virologic response. In contrast, early changes in PVL levels were not. Virologic failure was associated with detection of emergent DRMs. Virologic rebound in patients on salvage-HAART should be addressed aggressively.
National Institute for Infectious Diseases Lazzaro Spallanzani, 00149 Rome, Italy. tozzi@inmi.it
Valerio
V
Tozzi
Rita
R
Bellagamba
Filippo
F
Castiglione
Alessanda
A
Amendola
Jelena
J
Ivanovic
Emanuele
E
Nicastri
Raffaella
R
Libertone
Giampiero
G
D'Offizi
Giuseppina
G
Liuzzi
Caterina
C
Gori
Federica
F
Forbici
Roberta
R
D'Arrigo
Ada
A
Bertoli
Maria Flora
MF
Salvatori
Maria Rosaria
MR
Capobianchi
Andrea
A
Antinori
Carlo Federico
CF
Perno
Pasquale
P
Narciso
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016009:Chi-Square Distribution; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D012367:RNA, Viral; C514787:gp41 protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus