Development of the M184V Mutation in HIV-1 Infection and Subsequent Treatment Outcomes

Abstract

Objective: The purpose of this study was to describe the occurrence of the M184V mutation in a single clinic setting over a period of 10 years. We examined the combination Antiretroviral Therapy (cART) being taken at the time of first identification of the M184V mutation as well as Second Line Regimens (SLR) started immediately after the documentation of M184V. SLR were evaluated for frequency and time to Virologic Suppression (VS) as well as frequency and time to subsequent Virologic Failure (VF). Design: This was a retrospective cohort study of all Human Immunodeficiency Virus (HIV)infected patients receiving care at the Washington University School of Medicine Infectious Disease Clinic in St. Louis, MO, USA between January 2001 and June 2010. Methods: Prevalence of the M184V mutation, ART regimen leading to M184V acquisition, and outcomes of SLR in patients with M184V (as measured by time to initial VS and subsequent VF on SLR) were analyzed in a retrospective cohort study of all HIV-infected persons receiving care at a university clinic. Results: Of 2500 screened clinic patients, 220 had an acquired MI184V mutation (8.8%). There were 158(72%) male and 171(78%) African-American patients. The mean time from the start of a regimen to the documented M184V mutation was 575(0-3253) days. Independent of Nucleoside Reverse Transcriptase Inhibitor (NRTI) backbone, the mean time to development of M184V in Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) (n=109) and Protease Inhibitor (PI) based (n=84) regimens was 538(+/556) and 622 (+/620) days, respectively (p=0.325) approximately, 78% of patients achieved VS on a SLR in a mean of 179 days. Of the 122(57%) of patients whose SLR retained FTC/3TC, VS was achieved in 80% compared to 74% without FTC/3TC (p=0.285) with no significant difference in time to VS (152(+/187) and 181(+/257) days respectively, p=0.406). There were no significant differences in achievement of VS in PI (n=158) and NNRTI (n=27) – based SLRs independent of the NRTI backbone, 76% vs. 78%, respectively (p=0.837) with a similar time to VS (180(+/228) vs. 128(+/158) days, p=0.313). All patients on PI+Raltegravir (RAL) (n=10) and PI+NNRTI (n=12) – based regimens achieved VS (vs. 76% in PI+2NRTI (p=0.078 and p=0.054, respectively). Regardless of SLR, about 50% of each group experienced VF after VS with a similar time to failure. Conclusions: M184V mutation developed in 9% of patients in a mean of 575 days with no significant differences between ART regimens. Following initiation of an SLR, the majority of patients achieved VS in approximately 179 days irrespective of the regimen. The addition of 3TC/FTC did not significantly affect VS. Although numbers were small, 100% of patients on two fully active non-NRTI-backbone-based regimens attained VS. Approximately half of all patients subsequently failed on SLR, regardless of regimen used, suggesting that the development of M184V is a marker of noncompliance to therapy.