Adherence to non-nucleoside-based regimens may be less demanding

Antiretroviral regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) may successfully control viral load at adherence levels significantly lower than 95%, according to a study and editorial published in Clinical Infectious Diseases.

High levels of adherence to antiretroviral therapy are required to maintain HIV viral load suppression and avoid drug resistance. A widely-cited study, in 2000, showed that the success rates of triple-drug regimens based on protease inhibitors dropped off sharply for adherence rates less than 95%. On the strength of this and similar studies, 95% or better adherence has been generally cited as necessary for continued treatment success.

This study, however, used combinations of two nucleoside analogues plus a single protease inhibitor, without the use of ritonavir to “boost” protease inhibitor levels. Since that time NNRTIs and “boosted” protease inhibitors have come into more common use. New data now suggest that non-nucleoside-based regimens can be successful even at considerably lower rates of adherence.

David R. Bangsberg and team at the University of California, San Francisco, have been studying a group of homeless or marginally housed HIV-positive adults, a group that would be expected to have serious challenges with medication adherence. The researchers found that most of the protease inhibitor-treated individuals had viral loads of less than 400 copies/ml only at adherence levels of 95% or better, consistent with earlier findings. However, the majority of NNRTI-treated individuals had viral loads below 400 copies/ml at adherence rates of above 54%. More of the NNRTI-treated group achieved viral suppression overall, and NNRTIs performed significantly better for those in the 54-73% adherence range.

Bangsberg’s group has been investigating a sample of 330 HIV-positive adults, known as the Research on Access to Care in the Homeless (REACH) cohort, enrolled from San Francisco homeless shelters, meal programs, and low-income hotels between July 1996 and April 2000. One hundred and ten of these individuals, 56 of whom are receiving protease inhibitors, and 54 on NNRTIs, are included in the current published study. All had a median of 14 months of prior antiretroviral therapy including nucleoside analogues, but were receiving their first protease inhibitor or NNRTI. In the protease inhibitor-treated group, the drugs in use were nelfinavir (64%), indinavir (27%), saquinavir (7%) and ritonavir (2%). NNRTIs were nevirapine (62%) and efavirenz (38%). The NNRTI and protease inhibitor groups had similar baseline characteristics. The study was not randomised.

Participants were followed over a median of 9.1 months. Blood draws were done monthly; viral load suppression was defined as “less than 400 copies/ml” so that results could be directly compared to earlier studies.

The average rate of adherence in the study group overall was 70%. To measure adherence, all participants were subject to unannounced pill counts: unscheduled visits were made every three to six weeks, at which antiretroviral medications were counted. (Unannounced visits make it less likely for participants to “cheat” by dumping unused medications.) Participants could choose to use pill organisers (“medisets” or “dosettes”); for those who did not, electronic pill bottle caps (MEMS) were used as another measure of adherence. Participants were divided into adherence rate quartiles (0-53%, 54-73%, 74-94%, and 95-100%) with roughly equal numbers in each group.

These published results now confirm earlier reports from this study: that moderate adherence to NNRTIs was more likely to lead to viral suppression than comparable adherence to protease inhibitors. Response rates at either end of the adherence scale were unsurprising with the best viral load suppression seen at adherence rates 95% or above, the poorest at rates 53% or below. Significant differences, however, showed up in the intermediate ranges. In particular, for adherence between 54% and 73%, response to NNRTIs was dramatically better than that to PIs (p = .02).

Similar results were seen in a recent study that found that adherence of above 75% to NNRTI regimens led to sustained viral load suppression, while rates of above 85% were needed with protease inhibitors. Neither this study nor Bangberg’s study looked at combinations based on ritonavir-boosted protease inhibitors, or newer protease inhibitors such as atazanavir: the outcome of moderate adherence to these more potent protease inhibitor regimens is still unknown.

These studies indicate that NNRTI-based regimens may be more “forgiving”, i.e., may tolerate poorer adherence than previously believed. This is reassuring in “real-world” situations where near-perfect adherence standards are difficult to meet. However, as Bangsberg states, “reduced disease progression and mortality improves with every increase in adherence level … these data do not alter the goal to achieve the highest level of adherence possible.”