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"No Treatment Options" No Longer a Growing Problem in Switzerland
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15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
Mark Mascolini
Swiss antiretroviral-treated people with no options for an effective standard regimen including a protease inhibitor (PI) or a nonnucleoside plus two nucleosides hit a low point between 2002 and 2004 and stayed there through 2007 [1]. Over the same period estimated prevalence of resistance mutations dropped from a range of 50% to 60% in 1999 (depending on the calculation method) to a range of 37% to 50% in 2007.
Swiss HIV Cohort Study (SHCS) investigators focused on 7861 people who took antiretrovirals between January 1999 and December 2007. Just under one third were women, 80% were white, and 12% were African. While 38% picked up HIV heterosexually, 35% got infected during sex between men, and 24% by injecting drugs. About 29% had AIDS. Whereas 39% began treatment with single or double nucleosides, 24% started with an early combination regimen, and 37% with a newer combination. (The poster did not define the difference between early and newer combinations.)
SHCS researchers split the cohort into four groups:
· 1411 people (23.5%) with a genotype-confirmed resistance mutation
· 1345 people (22.4%) with earlier virologic failure or treatment with a single- or double-nucleoside regimen
· 2459 people (41.0%) who reached and always maintained a viral load below 50 copies with therapy
· 782 people (13.0%) with an unknown resistance or response status
Defining the probability of resistance as 100% in the group with genotype-confirmed resistance, the SHCS team figured the risk of resistance conferred by at least one IAS-USA mutation for all three of the other groups (the "upper-bound" estimate") and for group 2 people without a resistance test at virologic failure (the "lower-bound estimate"). Finally, the researchers defined availability of future standard three-drug regimens by two methods:
· Genotypic approach: In people genotyped after they began therapy, a drug was considered inactive if it had a Stanford genotypic sensitivity score above 15.
· Treatment history approach: Drugs in a failing regimen were considered inactive. Cross-resistance was assumed within each nucleoside group (AZT or d4T, 3TC or FTC, ddI or abacavir, and tenofovir) if a nucleoside in that group failed, for all nonnucleosides if a nonnucleoside failed, and for all PIs except darunavir or tipranavir if an unboosted PI failed. (This is a strict way to estimate future options, since some drugs in a failing regimen often remain active, and since boosted PIs other than darunavir or tipranavir can sometimes control replication after failure of an unboosted PI.)
Compared with the 100% resistance rate in the group with genotype-identified mutations, estimated probability of resistance mutations in the other groups stood at:
· 79.7% (95% confidence interval [CI] 7.79 to 81.3) in the virologic failure group
· 27.4% (95% CI 23.2 to 32.1) in the sub-50-copy group
· 38.6% (95% CI 32.3 to 45.5) in the group with unknown resistance or response
Lower- and higher-bound estimates of resistance prevalence in 1999 were 49.7% and 60.6%. By 2007 the lower and higher estimates dropped to 37.5% and 52.1%.
By the genotypic approach for reckoning further standard treatment options, the proportion of people without such options rose from 8% in 1999 to 13% in 2004, then remained stable through 2007. By the treatment history approach, the proportion without further standard options dipped from 33% between 1999 and 2001 to 11% in 2002 and remained stable afterwards. The drop in 2002 correlated with tenofovir's arrival.
The genotypic approach figured that 67.0% of the cohort (95% CI 63.2 to 70.7) would respond to salvage therapy in 2007. The treatment history approach calculated a 66.4% salvage response rate in 2007 (95% CI 62.4 to 70.3). Among people with triple-class resistance or triple-class failure, SHCS statisticians predicted a 53.1% response rate (95% CI 47.2 to 58.9).
"Drug resistance still represents a significant problem in highly treated populations," the Swiss team concluded, but in countries with "a well-developed health care system," that problem "has become more manageable over time." Because the same probably does not hold true in developing countries, they added, "efforts to monitor [resistance] have to be put high on the agenda of [antiretroviral] scale-up."
Reference
1. von Wyl V, Yerly S, Boni J, et al. The proportion of individuals without further treatment options has stabilized at low levels in the Swiss HIV Cohort Study. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 896.
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