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HIV/AIDS Clinical Care for November 21, 2011SUMMARY AND COMMENT November 21, 2011 | Jonathan Z. Li, MD Resistance mutations were detected most frequently with AZT/3TC and during periods of low-level viremia. Reviewing: von Wyl V et al. Clin Infect Dis 2011 Nov 4; SUMMARY AND COMMENT Two studies — one conducted in New York City and the other nationwide — detail the rising incidence of HIV infection and syphilis among men who have sex with men. Reviewing: Pathela P et al. J Acquir Immune Defic Syndr 2011 Dec 1; 58:408 Torrone EA et al. J Acquir Immune Defic Syndr 2011 Nov 1; 58:328 FEATURE November 21, 2011
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SUMMARY AND COMMENT A newly developed strategy allowed definitive characterization of 96% of the samples evaluated. Reviewing: Alanio A et al. Clin Microbiol Infect 2011 Oct 17:1531 |
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Summary and Comment Lower Rates of Resistance with Newer ART RegimensResistance mutations were detected most frequently with AZT/3TC and during periods of low-level viremia. Although antiretroviral regimens containing AZT or lopinavir/ritonavir are falling out of favor in developed countries, they are still recommended by the WHO and used extensively in developing countries. These regimens confer a higher risk for the emergence of drug resistance than newer regimens, according to a recent analysis in the Swiss HIV Cohort Study. Researchers analyzed data from 2263 patients who initiated combination antiretroviral therapy (ART) between 1999 and 2010 with the most commonly used regimens in the larger cohort: - AZT/3TC + efavirenz
- Tenofovir + FTC (or 3TC) + efavirenz
- AZT/3TC + lopinavir/r
- Tenofovir + FTC (or 3TC) + lopinavir/r
- Tenofovir + FTC (or 3TC) + boosted atazanavir
At each viral-load measurement, patients were classified according to their risk for the emergence of drug resistance. Intermediate risk was defined as a detectable viral load  500 copies/mL, excluding blips, and high risk as a viral load >500 copies/mL. Using a simulation technique, the investigators then imputed the risk for emerging resistance with each regimen. During a mean 4.5 years of follow-up, 14% of participants experienced at least one intermediate-risk period and 5% experienced at least one high-risk period. Almost two thirds of resistance mutations occurred during an intermediate-risk period. Patients treated with AZT/3TC + efavirenz had a significantly higher rate of emerging resistance than any other treatment group (2.6 vs. 1.4–1.9 mutations per 100 person-years) — a difference driven largely by higher rates of both M184V/I and thymidine analogue mutations. Rates of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance were similar between the two efavirenz groups. Patients on boosted atazanavir had lower rates of emerging resistance than those on lopinavir/r, although the difference was not statistically significant. Comment: The finding that newer ART regimens are associated with a lower frequency of emerging resistance is consistent with the results of previous studies. Whether AZT or 3TC is to blame for the higher rate of NRTI mutations seen with AZT/3TC + efavirenz is unclear, given that most patients on tenofovir were also on FTC, and that 3TC use has been associated with a higher rate of resistance at virologic failure ( JW AIDS Clin Care Mar 8 2010). The explanation for these findings is likely related to the improved tolerability and longer half-lives of the newer NRTIs. The finding that most new resistance mutations occurred in patients with low-level viremia ( 500 copies/mL) again reinforces the idea that resistance mutations can accumulate even at relatively low viral loads and that early intervention may prevent the accumulation of additional resistance mutations. — Jonathan Z. Li, MD Dr. Li is an Instructor in Medicine at Brigham and Women's Hospital in Boston. He reports no conflicts of interest. Citation(s): von Wyl V et al. Incidence of HIV-1 drug resistance among antiretroviral treatment–naive individuals starting modern therapy combinations. Clin Infect Dis 2011 Nov 4; [e-pub ahead of print]. ( http://dx.doi.org/10.1093/cid/cir728) |
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