Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy.
BACKGROUND
Selection of preexisting minority variants of drug-resistant human immunodeficiency virus type 1 (HIV-1) can lead to virological failure in patients who receive antiretroviral therapy (ART) with low genetic resistance barriers. We studied treatment response and dynamics of minority variants during the first weeks of ART containing a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs), which is a regimen with a high genetic resistance barrier.


METHODS
Plasma samples obtained prior to initiation of ART from 109 patients with primary HIV infection and samples obtained during viral decay during early ART from 17 of these 109 patients were tested by allele-specific polymerase chain reaction for K103N and M184V variants.


RESULTS
K103N and/or M184V mutations were detected in 15 (13.8%) of 109 patients prior to ART as minority variants. No selection of these variants was observed within the first weeks of ART in 7 of 15 patients with preexisting drug resistance mutations, nor was any selection observed in 10 patients without preexisting drug resistance mutations. Most patients received ART immediately after diagnosis of HIV-1 infection, showed a rapid decrease in viral load, and experienced sufficient suppression of viremia for 48 months.


CONCLUSIONS
Minority variants, in particular viruses harboring the M184V mutation, were efficiently suppressed in patients with acute infection who received a ritonavir-boosted PI and 2 NRTIs (most regimens included lamivudine). Under this high genetic resistance barrier regimen, the M184V was not further selected.
Metzner
Karin J
KJ
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, Switzerland. Karin.Metzner@usz.ch
Rauch
Pia
P
von Wyl
Viktor
V
Leemann
Christine
C
Grube
Christina
C
Kuster
Herbert
H
Böni
Jürg
J
Weber
Rainer
R
Günthard
Huldrych F
HF
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D019438:Ritonavir