Increased Resilience to the Development of Drug Resistance with Modern Boosted Protease Inhibitor. Part 4
Demographic characteristics. Between August 1996 and November 2004, a total of 2350 antiretroviral‐naive participants (81.6% males) at least 18 years old started triple‐combination therapy in British Columbia and were eligible to participate in this study. Of these patients, 991 (42%) individuals initiated nonboosted PI–based regimens, 475 (20%) initiated boosted PI–based regimens, and 884 (38%) initiated NNRTI‐based regimens. The temporal change toward increasing prevalence of ritonavir‐boosted regimens in recent years reflects the changes in treatment guidelines over time. During a median of 4.8 years (IQR, 2.7–10.0) of follow‐up, a total of 6066 resistance tests were done, and resistance to at least one drug category developed in 650 (28%) patients. The development of drug resistance was associated with a higher pVL, history of injection drug use, NNRTI‐based regimens, starting therapy in 1996–1998, age, and higher adherence levels. Sex, AIDS diagnosis, and CD4 cell count were not significantly associated with the development of drug resistance.
Probability of drug‐resistance development. The univariate analysis for baseline characteristics showed that age, pVL, history of injection drug use, first regimen, year of first therapy, and adherence were associated with the development of drug resistance. The multivariate model predicted no difference in the odds of the development of key resistance mutations between nonboosted PI–based regimens (reference group) and NNRTI‐based HAART regimens (odds ratio [OR], 1.09 [95% confidence intervals {CI}, 0.84–1.42]) but greatly reduced odds for boosted PI–based regimens (OR, 0.42 [95% CI, 0.28–0.62]). A skewed, nonlinear relationship with adherence was confirmed, as was a strong association of resistance with increasing pVL. A weaker association with decreasing CD4 cell count, late start of therapy, and history of injection drug use was also observed. Of interest, after adjusting for other parameters, there was a reduction in the risk of detecting resistance in those who started HAART during 1999–2001 (OR, 0.83) or 2002–2004 (OR, 0.43), compared with those who started HAART during 1996–1998 (reference group).
There were no visible differences in the relationship when the data were stratified by CD4 cell count; however, when stratified by year of first therapy, the data indicated that individuals starting therapy during 1996–1998 presented the highest probabilities for the development of drug resistance, and this probability decreased linearly until 2002–2004. Furthermore, stratifying by pVL demonstrated that individuals in the baseline pVL <5 log10 copies/mL stratum had a considerably lower probability for the development of resistance than those with baseline pVL values 5 log10 copies/mL at equivalent levels of adherence.