Including any one of efavirenz, indinavir or abacavir in a HAART regimen, or combining indinavir + lamivudine (3TC) with either zidovudine (AZT) or stavudine (d4T), suppressed viral load longer than other antiretroviral combination in a cohort of 1235 patients, according to a study due to be published in the September 1st issue of Clinical Infectious Diseases.
The HIV Outpatients Study (HOPS) cohort is an observational study from nine clinics in eight US cities that has been ongoing since 1992. Researchers compared the 286 people (23.1%) who had achieved consistent undetectable viral load levels (defined as either less than 400 copies/mL or 50 copies/mL depending on the time period and test used) for more than two years with the 949 who did not, over the period January 1993 to December 2001. Those who had a single detectable viral load or ‘blip’ were considered not to have achieved consistent undetectable levels.
Those who achieved undetectable levels for longer than two years were more likely to be treatment naive, male, white, gay, a college graduate and privately insured and had lower viral loads and higher CD4 counts at baseline.
However, multivariate analysis that controlled for all of these factors found that certain antiretrovirals and HAART combinations appeared to be more effective in reducing viral load for longer periods of time. These were: efavirenz (odds ratio (OR) 5.2; p
Other drugs that were found to have statistically significant efficacy - although all had OR below 2.7 - were: 3TC alone, ritonavir, nelfinavir and nevirapine. However these were only found to be significant before adjusting for all the covariates as above. Although amprenavir, delavirdine and Kaletra were available during the study period, they were not included since they were introduced later than 1999, which meant they could not be evaluated for two years or more.
The authors do not suggest reasons why certain drugs were more effective, although an unpublished sub-analysis did find that adherence appeared not to be a factor. Tolerability, however, is likely to have been a factor, and although they report that 37.8% of those in the long-term undetectable group changed regimens due to drug toxicity or intolerance, no information is given for the comparison group, other than they were on an average of 5.7 regimens during the study period compared with an average of 2.0 in the long-term undetectable group.
Although efavirenz appears to show clear superiority over nevirapine in this study, the authors point out that this could have been a result of nevirapine being available before efavirenz and therefore used in suboptimal combinations, including simply adding nevirapine to a failing dual drug regimen.
Whilst the results of this study are unlikely to affect current clinical practice, they do call into question the influence of fashion and received wisdom on prescribing practice. Although indinavir showed a greater odds of durable viral suppression than nelfinavir in this large cohort analysis (with no overlap in confidence intervals), nelfinavir became the most prescribed protease inhibitor in the US during the period covered by the study due to perceptions about tolerability and equipotence with other PIs. Similarly the study shows the superiority of regimens combining 3TC with either indinavir or efavirenz, despite the strong arguments for commencing therapy with d4T and ddI advanced by some commentators during this period.
Further information on this website
US HIV guidelines: choose either lopinavir or efavirenz in first-line treatment - news story
2NN study shows nevirapine equal to efavirenz, but has better lipid profile - news story
Holmberg SD et al. Factors associated with maintenance of long-term plasma human immunodeficiency virus RNA suppression. Clin Infect Dis 37: electronically published 12 August 2003.