Correspondence
Drug Resistance among Patients Recently Infected with HIV
N Engl J Med 2002; 347:1889-1890December 5, 2002
- Article
To the Editor:
The retrospective analysis by Little et al. (Aug. 8 issue)1 provides further evidence of the transmission of drug-resistant human immunodeficiency virus type 1 (HIV-1)2 and attempts to relate detection of resistant virus before antiretroviral therapy to suboptimal virologic response. However, the authors' recommendations for universal base-line resistance testing and abandonment of empirical treatment are premature.
Ascertainment of base-line viral resistance is not recommended by the current guidelines except in cases of virologic failure or incomplete viral suppression after initial therapy.3 Little et al. did show that the time to viral suppression was shorter and the time to treatment failure was longer in patients infected with drug-susceptible virus; nevertheless, complete viral suppression was achieved in all but one patient by 24 weeks, regardless of the susceptibility patterns. In fact, the investigators attempted to determine whether inferior response rates were the result of the acquisition of resistant virus or the use of less active regimens. The number of active drugs did not significantly correlate with the time to viral suppression. Moreover, evidence from prospective studies (the VIRADAPT Study4 and the Genotypic Antiretroviral Resistance Testing Study5) supporting the usefulness of resistance testing involved patients with virologic failure, not patients initiating therapy.
Base-line determination of resistance should not direct a clinician's choice of antiretroviral agents at this time, since it is unlikely to affect initial viral suppression substantially. On the contrary, it may result in the avoidance of potentially effective regimens and premature abandonment of active agents in an arena in which our arsenal is already limited.
5 ReferencesBenjamin J. Epstein
University of Florida College of Pharmacy, Gainesville, FL 32608
bj45@ufl.edu 1
Little SJ ,Holte S ,Routy J-P , et al. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med 2002;347:385-394
Full Text | Web of Science | Medline2
Little SJ ,Daar ES ,D'Aquila RT , et al. Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA 1999;282:1142-1149
CrossRef | Web of Science | Medline3
Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Washington, D.C.: Department of Health and Human Services, February 2002.
4
Durant J ,Clevenberg P ,Halfon P , et al. Drug resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999;353:2195-2199[Erratum, Lancet 1999;354:1128.]
CrossRef | Web of Science | Medline5
Baxter JD, Mayers DL, Wentworth DN, Neaton JD, Merigan TC, CPCRA 046 Study Team. A pilot study of the short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy. In: Program and abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999. abstract.
Author/Editor Response
The authors reply:
To the Editor: Although complete viral suppression was achieved by week 24 in all but 1 of 202 subjects with primary HIV infection who were treated with potent antiretroviral therapy, in a combined analysis of four treatment trials conducted by the AIDS Clinical Trials Group, complete viral suppression was often followed by virologic rebound that was not predicted by the initial response to treatment.1 In that analysis, virologic response to therapy was characterized for 1518 patients between weeks 0 and 24 to determine possible predictors of “off-track” or suboptimal responses to treatment.1 The initial virologic responses were similar among patients in whom complete viral suppression was achieved and those who had a rebound of viremia during treatment, until the first measure of virologic failure, which was typically associated with an abrupt virologic rebound that was not related to an initial suboptimal response to treatment.
We do not believe that the observed high rate of viral suppression in our study should be considered equivalent to successful treatment. Rather, sustained viral suppression should be the hallmark of successful treatment. The longer time needed to achieve complete viral suppression in patients with drug-resistant virus may permit sufficient additional rounds of viral replication to select for additional drug-resistant variants during this initial treatment period,2 particularly in patients who present with primary HIV infection and higher viral loads than are typically observed at later stages of HIV infection. Responses to antiretroviral treatment in subjects who have not previously received treatment are generally superior to those in subjects who have previously received treatment.3 Furthermore, there is an association between the number of drug-resistance mutations at base line and subsequent treatment failure among patients who have previously received treatment and are receiving salvage therapy.4 We believe these data, in addition to our observations regarding the response to treatment, support the usefulness of routine screening for drug resistance in recently infected patients.
4 ReferencesSusan J. Little, M.D.
Douglas D. Richman, M.D.
University of California, San Diego, San Diego, CA 92103
slittle@ucsd.edu 1
Huang W ,De Gruttola V ,Fischl M , et al. Patterns of plasma human immunodeficiency virus type 1 RNA response to antiretroviral therapy. J Infect Dis 2001;183:1455-1465
CrossRef | Web of Science | Medline2
Bonhoffer S ,May RM ,Shaw GM ,Nowak MA . Virus dynamics and drug therapy. Proc Natl Acad Sci U S A 1997;94:6971-6976
CrossRef | Web of Science | Medline3
Ledergerber B ,Egger M ,Opravil M , et al. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study: Swiss HIV Cohort Study. Lancet 1999;353:863-868
CrossRef | Web of Science | Medline4
Lorenzi P ,Opravil M ,Hirschel B , et al. Impact of drug resistance mutations on virologic response to salvage therapy: Swiss HIV Cohort Study. AIDS 1999;13:F17-F21
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Lori Wiener, Claude Ann Mellins, Stephanie Marhefka, Haven B. Battles. (2007) Disclosure of an HIV Diagnosis to Children: History, Current Research, and Future Directions. Journal of Developmental & Behavioral Pediatrics 28:2, 155-166
CrossRef
