HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure.
BACKGROUND
The clinical implications of emergent HIV drug resistance on samples with low-level viraemia (LLV <1000 copies/ml) remain unclear. We undertook the present analysis to evaluate the impact of emergent HIV drug resistance at LLV on the risk of subsequent virologic failure.


METHODS
One thousand, nine hundred and sixty-five patients had genotype results at LLV. Risk of virologic failure (≥1000 copies/ml) after LLV was evaluated by Kaplan-Meier analysis and Cox proportional hazards regression. Resistance was assessed using the Stanford algorithm or virtual phenotypes. Patients were grouped into four susceptibility categories ('GSS' or 'vPSS') during LLV, corresponding to the number of 'active' drugs prescribed: <1; 1-1.5; 2-2.5; and ≥3.


RESULTS
A total of 1702 patients with follow-up on constant therapy were eligible for analysis. Participants excluded due to changing therapy or loss to follow-up before their next observation had mostly similar characteristics to included participants. There was a 'dose-dependent' increase in the hazard ratio for virologic failure with susceptibility categories at LLV. Compared with a GSS of at least 3, hazard ratios for virologic failure were 1.4 for GSS 2-2.5; 2.0 for GSS 1-1.5; and 3.0 for GSS less than 1 (P < 0.001). Numerous sensitivity analyses confirmed these findings.


CONCLUSIONS
Our results demonstrate that emergent HIV drug resistance at LLV is strongly associated with subsequent virologic failure. Furthermore, we uncovered a 'dose-dependent' increase in the hazard ratio for virologic failure with decreasing GSS estimated at the time of LLV. On the basis of these findings, we propose that resistance genotyping be encouraged for HIV-infected individuals on antiretroviral therapy experiencing low-level viraemia.
aBC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada bBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Luke C
LC
Swenson
Jeong Eun
JE
Min
Conan K
CK
Woods
Eric
E
Cai
Jonathan Z
JZ
Li
Julio S G
JS
Montaner
P Richard
PR
Harrigan
Alejandro
A
Gonzalez-Serna
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000821:virology*
D044966:Anti-Retroviral Agents