Accrued HIV evidence turns treatment dogma on its head

From: BiGoldberg@aol.com
Newsgroups: sci.med.aids
Approved: Yes: Marty Howard <martinjh@marty-howard.com>,"David Clay" <daveyc@centurytel.net>
Subject: Accrued HIV evidence turns treatment dogma on its head & 8/21 Nature
Message-ID: <68529@sci.med.aids>
Date: Wed, 20 Aug 2003 19:15:37 CDT
Organization: unspecified

Nature, 21 August 2003, Vol. 424, Page 866

Erika Check, Washington

A series of studies has dispelled the widespread notion that patients
who don't take every dose of their anti-HIV medication create a
public-health risk by helping to nurture HIV strains that resist
therapy.

The findings suggest instead that some patients who do not take all of
their medicine are actually less likely to become resistant to therapy
than those who adhere rigidly to their doctors' instructions.

. . .

---------------------------------

AIDS 2003 Sep 5; 17(13):1925-1932

High levels of adherence do not prevent accumulation of HIV drug
resistance mutations

David R. Bangsberg a,b; Edwin D. Charlebois a; Robert M. Grant c; Mark
Holodniy e; Steven G. Deeks b; Sharon Perry f; Kathleen Nugent Conroy f;
Richard Clark d; David Guzman a; Andrew Zolopa f; Andrew Moss d

Objectives:

To assess the relationship between development of antiretroviral drug
resistance and adherence by measured treatment duration, virologic
suppression, and the rate of accumulating new drug resistance mutations
at different levels of adherence.

Methods:

Adherence was measured with unannounced pill counts performed at the
participant's usual place of residence in a prospective cohort of
HIV-positive urban poor individuals. Two genotypic resistance tests
separated by 6 months (G1 and G2) were obtained in individuals on a
stable regimen and with detectable viremia (> 50 copies/ml). The primary
resistance outcome was the number of new HIV antiretroviral drug
resistance mutations occurring over the 6 months between G1 and G2.

Results:

High levels of adherence were closely associated with greater time on
treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148
individuals. In a subset of 57 patients with a plasma viral load > 50
copies/ml on stable therapy, the accumulation of new drug resistance
mutations was positively associated with the duration of prior treatment
(P = 0.03) and pill count adherence (P = 0.002). Assuming fully
suppressed individuals (< 50 copies/ml) do not develop resistance, it
was estimated that 23% of all drug resistance occurs in the top quintile
of adherence (92-100%), and over 50% of all drug resistance mutations
occur in the top two quintiles of adherence (79-100%).

Conclusion:

Increasing rates of viral suppression at high levels of adherence is
balanced by increasing rates of drug resistance among viremic patients.
Exceptionally high levels of adherence will not prevent population
levels of drug resistance.

From the aEpidemiology and Prevention Interventions Center, Division of
Infectious Diseases and the bPositive Health Program, San Francisco
General Hospital, the cGladstone Institute of Virology and Immunology
and the dDepartment of Epidemiology and Biostatistics, University of
California at San Francisco, the eAIDS Research Center, VA Palo Alto
Health Care System and fStanford University School of Medicine, Palo
Alto, California, USA.

Requests for reprints to: Dr D. R. Bangsberg, Box 1372, San Francisco
General Hospital, UCSF, 1001 Potrero Avenue, Building 100, Room 301, San
Francisco, California 94110, USA.