Initial HAART regimen lasts only 1.6 years in antiretroviral-naive

HAART is supposed to be a lifelong commitment once therapy has begun, but according to a study due to be published in the September 1st issue of Clinical Infectious Diseases, the median duration of an initial HAART regimen amongst 405 previously antiretroviral naive patients at an outpatient clinic in the US was only 1.6 years. Given that the study also shows that each successive HAART regimens is less durable than the initial regimen, the concept of lifelong therapy possibly requires reassessment - unless better drugs continue to be made available.

A previous “real life” study of the HOPS cohort by Palella and colleagues found that the median duration of initial HAART regimens was 11.8 months, with the second and third regimens lasting 7.4 and 7.2 months, respectively. The study found that those who were antiretroviral-naive were on their initial combination longer than the median, inspiring this study from the University of Alabama at Birmingham Outpatient HIV Clinic.

The authors followed 405 treatment-naive patients of the 1206 in total who began HAART on or after January 1996, up until October 9, 2001. The median baseline CD4 count and viral load was 197 cells/mm³ and 70,146 copies/mL, respectively. Almost 60% changed from their initial regimen (n=240). but around 35% (n=140) remained on their initial regimen to the end of the study period. After four years, 11 of 45 (24.4%) for whom follow-up data were available were still receiving their initial regimen.

Amongst the total cohort, the median duration of initial HAART was 581 days (1.6 years). The median length of second, third and fourth regimens was 324, 218 and 112 days, respectively.

The only factors that were significantly associated with risk of discontinuing HAART were injection drug use and a previous OI in both univariate and multivariate analysis, with injection drug use being the most significant factor (hazard ratio 2.17; 95% CI 1.42-3.29; p = 0.0003). The authors found that this was not due to injection drug users presenting at a later stage of HIV disease progression, nor to poor adherence, and suggest that socio-economic or other factors may explain this risk, although they were unable to adequately assess this.

The only individual drug associated with risk of discontinuation in univariate analysis was saquinavir soft gel capsule, Fortovase. However, since only 10 patients were on this drug, the significance of this finding should not be over-interpreted. No difference in the duration of HAART regimen was seen based on year of initiation.

A manual review of the charts was undertaken to assess why initial regimens were discontinued. Overall, almost 50% were due to toxicity, most notably nausea and vomiting (12.9%). Those who discontinued therapy within 90 days (n=56) were particularly affected by nausea and vomiting (25%) and anaemia (17.9%). Poor adherence and/or virological failure - which were impossible to separate in this “real life setting” - was the next most common reason, accounting for 22.5% of the total. Despite this, the median CD4 cell count and viral load of the 240 individuals who changed from their initial regimen was substantially higher than baseline at time of change, at 343 cells/mm³ and 303 copies/ML, respectively, although since data from 41 patients were missing, the data could be somewhat unrepresentative of the total cohort.

25% of patients who discontinued their initial HAART therapy did so within 90 days, and it was found that those who managed to get past 90 days stayed on therapy an average of four months longer than the 1.6 year median.

Whilst the authors found that just over 20% of patients were still taking their first regimen in their fourth year of treatment, a further 18% of patients had moved to their fourth HAART regimen by this point, illustrating the ongoing need for new agents to meet the needs of those who cannot tolerate existing treatments.