Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jun 1;72(2):171-6.
doi: 10.1097/QAI.0000000000000942.

Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance

Dana S Clutter  1 , W Jeffrey Fessel, Soo-Yon Rhee, Leo B Hurley, Daniel B Klein, John P A Ioannidis, Michael J Silverberg, Robert W Shafer
Affiliations

Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance

Dana S Clutter et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance.

Methods: We reviewed treatment outcomes in a cohort of HIV-1-infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression.

Results: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01).

Conclusions: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered.

PubMed Disclaimer

Conflict of interest statement

D.S.C. was supported by a grant for this work (T32 AI052073) from the National Institutes of Health. S.-Y.R. and R.W.S. were also supported by a grant (R01 AI068581) from the National Institutes of Health. D.S.C. to receive research funding through the Bristol-Myers Squibb Virology Fellows Research Program in March 2016. R.W.S. is a consultant for Celera, and receives research funding from Roche Molecular, Gilead Sciences, Bristol-Myers Squibb, and Merck. The other authors have no funding or conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
The Kaplan–Meier plot shows the cumulative incidence of patients free of failure events per the as-treated analysis according to the anchor-drug class. The as-treated analysis failure outcome was VF, defined as not reaching an undetectable HIV-1 RNA level by 24 weeks, virological rebound, and regimen switching during viremia. The P value was calculated by the log-rank test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Wheeler WH, Ziebell RA, Zabina H, et al. Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S.-2006. AIDS. 2010;24:1203–1212. - PubMed
    1. Li J, Kim D, Linley L, et al. Sensitive screening reveals widesperad underestimation of transmitted HIV drug resistance [87]. Presented at: Conference on Retroviruses and Opportunistic Infections; March 3–6, 2014; Boston, MA.
    1. Ocfemia MCB. Epidemiology of HIV-1 transmitted drug resistance among men who have sex with men in the United States [81]. Presented at: XXIV International HIV Drug Resistance Workshop; February 21–22, 2015; Seattle, WA.
    1. Rhee SY, Blanco JL, Jordan MR, et al. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. PLoS Med. 2015;12:e1001810. - PMC - PubMed
    1. Oette M, Kaiser R, Daumer M, et al. Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr. 2006;41:573–581. - PubMed

Publication types

Substances