Discontinuation rates similar between HAART regimens

Highly active antiretroviral therapy (HAART) can be very effective in suppressing HIV but it also can be very difficult to take and tolerate.

Thus, while studies indicate that some HAART regimens may have high rates of virologic success at the end of one year, other studies indicate that up to 25% of patients discontinue their initial HAART regimen within one year of starting it.

A recent study published in AIDS evaluated HAART discontinuation rates among patients who started HAART using either a protease inhibitor (PI)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen. The investigators utilized the Italian cohort of Antiretroviral-Naïve Patients database beginning in March 1997 and continuing until May 2000. This study included 2002 patients who began antiretroviral therapy with a 3 drug HAART regimen and had at least one follow-up visit. The primary endpoint was the date of discontinuation of the initial HAART regimen or any component of it.

The large majority of patients involved in the study began HAART using a PI-based regimen, with 85.4% starting HAART with a PI versus 14.6% with an NNRTI. The median duration of follow-up was 9.7 months with 70% of the patients being men and the majority having intravenous drug use as their HIV risk factor. The median baseline CD4+ T cell count and viral load were 290 cells/mm3 and 4.7 log10 copies/mL for those patients starting a PI-based regimen versus 428 cells/mm3 and 4.4 log10 copies/mL in patients starting with an NNRTI.

Eight hundred and fifty-seven (42.8%) of all patients discontinued their HAART regimen within the study period. Of the 1709 patients that started therapy with a PI, 777 (45.5%) discontinued therapy, while of the 293 patients that started with an NNRTI, 80 (27.3%) discontinued therapy. No significant difference was found between PI- and NNRTI-based HAART regarding time to discontinue therapy. The primary reasons given by the patients for discontinuing therapy were regimen toxicity (42.7%), virologic failure (28.5%) and nonadherence (23%). No significant difference was found between the patients on a PI or an NNRTI regarding the reason for discontinuation, but patients on an NNRTI-based regimen tended to have fewer discontinuations due to virologic failure. Other significant predictors of discontinuation included female sex and higher baseline viral load.

The authors conclude, “In conclusion, when considering discontinuation for toxicity of non-compliance, no difference was found in the probability of discontinuation by the type of initial regimen. When the reason for discontinuation was failure, individuals undergoing an NNRTI-containing regimen tended to be less likely than those undergoing a PI-containing regimen to discontinue HAART, although the difference was not statistically significant. Additional follow-up will be necessary to confirm the difference and to determine its reasons.”

Comment

Although the proportion of patients discontinuing was significantly different between the regimens (45.5% PI, 27.3% NNRTI), the rate of discontinuation was similar. This is due to a difference in the median duration of follow-up for those on PI versus those on NNRTI based regimens (11 months PI and 5.6 months NNRTI).

It should also be noted that the similar discontinuation rates between the regimens occurred despite the fact that the PI cohort were significantly more advanced in their HIV-disease (median baseline CD4 290 cells/mm3 for PI versus 428 cells/mm3 for NNRTI). The majority of patients in this cohort were male with injecting drug use as route of infection.

Dorrucci M et al. Time to discontinuation of the first highly active antiretroviral therapy regimen: a comparison between protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-containing regimens. AIDS. 2001; 15:1733-1736.
http://www.ncbi.nlm.nih.gov/pubmed/11546952?dopt=Abstract