HIV
and Hepatitis.com Coverage of the 14th
Annual Conference on Retroviruses and Opportunistic Infections (14th CROI) February
25 - 28, 2007, Los Angeles, CA
U.S. Studies Show 10%-15% of Newly-diagnosed Individuals Have Drug-resistant HIV By
Liz Highleyman
It is well known that suboptimal or prolonged
antiretroviral therapy can
lead to the emergence of drug-resistant
HIV. But resistance is also a growing problem among newly infected individuals
who have never received antiretroviral agents themselves, presumably because they
acquire virus that has already developed drug-resistance
mutations.
In
the largest study, W. Wheeler and colleagues used data from the U.S. Centers for Disease Control and Prevention
(CDC) Variant, Atypical, and Resistant HIV Surveillance system (VARHS), analyzing blood specimens from
more than 3000 newly diagnosed treatment-naive individuals who underwent confidential
HIV testing at 409 sites (e.g., HIV test sites, sexually transmitted
disease [STD] clinics, private physicians, hospitals) in 11 states between January 2003
and October 2006.
The investigators identified major antiretroviral drug resistance
mutations categorized according to International AIDS Society guidelines and derived HIV subtypes using the Stanford online HIV Drug
Resistance Database.
Results
Based
on 3130 analyzed specimens, 327 individuals (10.4%) showed evidence of drug-resistance
mutations.
In
various participating states, rates ranged from 6.3% to 13.0%.
Looking
at specific drug classes, the resistance rates were:
60
individuals (1.9%) showed evidence of multiple drug-resistance mutations:
44
subjects (1.4%) had mutations conferring resistance to at least 1 agent in 2 classes;
16
subjects (0.5%) had resistance to drugs in all 3 major antiretroviral drug classes.
The researchers concluded that these findings -- based on the largest
and most diverse U.S.
population-based sample to date -- have implications for initial treatment of
newly diagnosed individuals. “These findings also emphasize the importance of
ongoing molecular HIV surveillance in the United States,” they said.
In
another study, N. Zetola and colleagues analyzed the presence of drug-resistant
HIV among 402 newly diagnosed individuals in San
Francisco between 2004 and 2006. This analysis included
subjects tested at HIV test sites and STD clinics, as well as a cohort of participants
in a study of acute HIV infection.
Results
•
55 of the 402
tested subjects (13.7%) had evidence of drug-resistant HIV:
•
NNRTI
resistance was most common, at 9.5%;
•
About
3% had multidrug resistance, including 0.7% with 3-class resistance.
The
investigators concluded that, "Transmitted drug resistance was modest in
frequency and not increasing in newly identified HIV cases in San Francisco."
In fact, contrary to some past reports, this study found that the prevalence
of drug-resistant HIV among newly diagnosed individuals actually declined between
2005 and 2006.
Univ of California at San Francisco; San Francisco Dept
of Public Health; Gladstone Inst of Virology and Immunology; AIDS Health Project,
San Francisco, CA.
A.
Low and colleagues looked at rates of drug resistance in 108 individuals with
acute or recently acquired HIV infection, diagnosed between January 2005 and December
2006 in New York City.
Results
•
The
overall rate of resistant HIV was 12.8%.
•
The
rate of NNRTI resistance was 9.3%.
•
The
rate of multidrug resistance was 4.6%.
•
Rates
of drug resistance declined significantly compared with a similar survey conducted
in 2003-2004, in which the overall resistance rate (27.1%) and the multidrug resistance
rate (4.6%) were more than twice as high.
•
However,
the rate of NNRTI resistance remained comparable The researchers concluded
that, "The transmission of drug-resistant virus in this homogenous cohort
is trending downward, possibly due to better adherence to current regimens in
the local HIV-1-infected population."
Aaron
Diamond AIDS Research Ctr, Rockefeller Univ, New York, NY.
Finally,
a study by C. de Mendoza and colleagues looked at rates of transmitted drug resistance
in Spain. This study included about 350 consecutive recent HIV seroconverters
(12 months or less since exposure) seen between January 1997 and September 2006
at 15 hospitals across the country. Results
•
Overall, 14.7% showed
evidence of antiretroviral resistance mutations in the most recent study period
(2005-2006).
•
Resistance
to NNRTIs was most common (about 10%), followed by NRTIs (about 4.5%), then PIs
(about 3.5%).
•
Resistance
was most common in 1997-1999 (29%), then declined significantly in 2000-2001 (5.3%).
•
However,
the rate of resistance then began to rise again, reaching 10.7% in 2002-2004 and
14.7% in 2005-2006.
“A significant
proportion…of recent HIV-1 seroconverters in 2005-2006
harbor drug-resistance mutations, which represents an increase with respect
to prior years,” the investigators concluded. “Moreover, PI-resistant
and multidrug-resistant viruses have become more frequent in recent years.”
Hosp
Carlos III, Madrid; Ctr Sanitario Sandoval, Madrid; Hosp Gen, Elche; Hosp Vall
d'Hebron, Barcelona; Hosp de la Ribera, Valencia; Hosp Xeral, Santiago; Hosp Marques
de Valdecilla, Santander; Hosp Gen, Valencia; Hosp Reina Sofia, Cordoba, Spain.
Taken together, these studies all found rates
of transmitted drug resistance between 10% and 15%. There was some indication
that this may be decreasing, especially in the U.S., perhaps
due to more effective antiretroviral therapies and better adherence.Nevertheless,
the prevalence of drug-resistant HIV remains a concern, and suggests that newly
diagnosed individuals should undergo resistance testing before starting treatment,
as recommended by the most recent DHHS
treatment guidelines.
04/06/07
References
W Wheeler, K Mahle, Ulana Bodnar (U.S. Variant,
Atypical and Resistant HIV Surveillance Group). Antiretroviral
Drug-resistance Mutations and Subtypes in Drug-naïve Persons Newly Diagnosed with
HIV-1 Infection, US, March 2003 to October 2006. 14th Conference on Retroviruses and
Opportunistic Infections (CROI). Los
Angeles, February 25-28, 2007. Abstract 648 (poster).
N Zetola, K Ahrens, C Kent, and others. Surveillance
for Transmitted Drug-resistance in Sentinel-sites: San Francisco, 2005-2006. 14th
CROI. Abstract 652 (poster).
A Low, H Mohri, M Markowitz. Recent Trends
in Transmitted Drug Resistance in a New York City Cohort. 14th CROI. Abstract 651
(poster).
C de Mendoza, C Rodriguez, F Gutierrez,
and others. Transmission of HIV Strains with Resistance
to PI and to Multiple Drug Classes Is Growing in Spain. 14th CROI.
Abstract 656 (poster).
In
another study, N. Zetola and colleagues analyzed the presence of drug-resistant
HIV among 402 newly diagnosed individuals in 
A.
Low and colleagues looked at rates of drug resistance in 108 individuals with
acute or recently acquired HIV infection, diagnosed between January 2005 and December
2006 in New York City. 
Finally,
a study by C. de Mendoza and colleagues looked at rates of transmitted drug resistance
in Spain. This study included about 350 consecutive recent HIV seroconverters
(12 months or less since exposure) seen between January 1997 and September 2006
at 15 hospitals across the country.
