Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral combination therapy.
OBJECTIVE
To study the appearance of drug-induced mutations at low viraemia in treated HIV-1-infected patients.


METHODS
Fourteen patients, who received their first (n = 5), second (n = 7) or third (n = 2) line antiretroviral combination therapy, developed a persistent low-grade viraemia after an initial decrease of the viral load (VL) to less than 500 copies/ml. The amount of HIV-1 RNA (n = 71) and reverse transcriptase (RT)/protease sequences (n = 56) were determined in longitudinally obtained plasma samples during a mean period of 16.6 months.


RESULTS
In the vast majority (93%) of patients, new primary resistance mutations were found in the RT and/or protease genes at virological failure at a median VL of 500 and 200 copies/ml, respectively. Drug-experienced patients developed mutations at a lower VL than naive patients. In one previously protease inhibitor-naive patient, primary RT and protease mutations were detected, although the VL was less than 50 copies/ml. A serial accumulation of drug resistance mutations was seen despite the VL increase being mostly modest, reaching a median of 1450 copies/ml at the end of the study, and the CD4 T cell counts continued to increase. One patient still had a VL of 300 copies/ml after 28 months, despite the presence of the multidrug-resistance Q151M mutation.


CONCLUSIONS
Low viraemia after virological treatment failure can select for virus with several new drug resistance mutations, despite a concomitant increase in CD4 T cell counts. This serial accumulation of mutations is likely to exhaust future drug options
Aleman
Soo
S
Division of Clinical Virology, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
Söderbärg
Karin
K
Visco-Comandini
Ubaldo
U
Sitbon
Gisela
G
Sönnerborg
Anders
A
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012641:Selection, Genetic; D013548:Sweden / Q000453:epidemiology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000453:epidemiology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease