Overall, 542 patients who started initial ARV therapy during the study period met eligibility criteria and are included in this study. Patient and regimen characteristics were calculated for the overall sample, and then by time period of ART initiation (). The majority of patients were black (55%), male (77%) and lacked private health insurance (51%). The mean age of the sample was 37.9 ± 9.9 years, and intravenous drug use was an infrequently reported HIV risk factor (8%), while a history of men having sex with men (50%) was most commonly reported. Affective mental health disorders were diagnosed in 45% of the sample, while 23% had substance abuse disorders. The baseline log10 plasma HIV RNA was 4.7 ± 1.0 copies/mL and 56% of patients had initial CD4 counts<200 cells/mm3. Compared to patients starting ARV therapy between 1 January 2000 - 31 July 2004, those starting after August 2004 were less likely to have private health insurance, less likely to have alcohol abuse disorders, and had higher baseline CD4 counts ().
Baseline characteristics of 542 antiretroviral-naïve patients starting their initial ARV regimen at the UAB 1917 HIV/AIDS Clinic; January 2000 - July 2007.
In the overall evaluation of regimens prescribed during the study period, NNRTI-based therapy was most commonly used (). Two-thirds of regimens consisted of 3 or fewer pills, and 85% contained a fixed-dose combination antiretroviral agent. A marked and statistically significant increase in the use of fixed-dose combination antiretrovirals (77% to 95%) and once-daily regimens (12% to 82%) was noted when comparing regimens started in the earlier time period to those started after August 2004. The use of ABC or TDF as part of an NRTI backbone grew from 6% in the earlier period to 85% for regimens started after August 2004, while AZT use dropped from 77% to 14% in the latter time period. Increased use of both boosted PI (7% to 23%) and NNRTI regimens (68% to 72%) was observed, while triple NRTI regimen use ceased altogether (16% to 0%) in the study period after August 2004. Finally, a statistically significant decline in regimen discontinuation within 90 days of initiation (p<0.01) was observed between the earlier and latter time periods (14% vs. 6%).
The median duration of the initial ART regimen increased by 263 days between the earlier (780 days) and more recent (1043 days) study periods (). Initial ART regimen duration for both periods eclipsed the observed median of 595 days for regimens initiated between 1 January 1996 and 31 December 1999.
Figure 1 Legend: Regimens started after 8/1/04 (n=233) achieved a median durability of 1043 days (95%CI = 735-NA) vs. 780 days (95%CI = 593-992) for regimens started between 1 January 2000 - 31 July 2004 (n=309). The final curve represents regimens started during (more ...)
Next, we evaluated the roles of dosing complexity and antiretroviral composition of regimens as they relate to initial ART regimen durability using KM plots and the log rank test. First, we evaluated regimen duration as a function of pill burden, demonstrating that regimens containing ≤ 3 pills achieved the greatest longevity (median 1,218 days) and those consisting of ≥ 6 pills, the shortest (median 340 days) (). Once daily regimens (1,253 days) lasted a median 541 days longer than regimens dosed ≥ twice a day (712 days) (). Next the composition of regimens was evaluated. Regimens containing DDI or D4T exhibited the shortest durability (450 days), while regimens including ABC or TDF had the longest durability (median 1,253 days) (). Finally, when comparing third drugs by class, NNRTI based regimens (median 1,132 days) had the greatest longevity followed by boosted-PI (median 1,043 days), triple NRTI (median 662 days), and unboosted PI regimens (median 382 days) ().
Figure 2 Legend: Duration of initial ARV regimens as a function of regimen dosing complexity. 2a) Pill burden: Regimens ≤ 3 pills per day (n=358) achieved a median durability of 1,218 days (95%CI = 961-1,724) as compared to a median durability of 766 days (more ...)
Figure 3 Legend: Duration of initial ARV regimens per regimen composition. 3a) NRTI: regimens containing stavudine (D4T) and/or didanosine (DDI) (n=54) have the shortest median duration 405 days, while those utilizing zidovudine (n=271) achieved a median duration (more ...)
Staged Cox PH models were fit to first evaluate the role of study period on regimen longevity while controlling for patient factors, and then sequentially adding dosing frequency (BID vs. QD) and antiretroviral composition of regimens (NRTI agents and third drug class) to successive models to evaluate the role of these factors in contributing to greater longevity of regimens started in more recent years (). When controlling for patient factors, regimens started between 1 January 2000 - 31 July 2004 had significantly increased hazards of discontinuation relative to regimens started after August 2004 (HR 1.44, 95%CI 1.03-2.02) (, Model 1). When dosing frequency was added to the model (, Model 2), time period of ARV initiation was no longer significant, while ≥ twice daily dosing frequencies had nearly double the hazard of regimen discontinuation relative to once daily regimens (HR 1.92, 95%CI 1.29-2.88). In the final model regimen composition variables were added to the model (, Model 3). All third drug classes were found to have greater hazards of discontinuation relative to NNRTI based regimens (triple NRTI HR 1.76, 95%CI 1.14-2.73; unboosted-PI HR 1.58, 95%CI 1.02-2.46; boosted-PI HR 1.57, 95%CI 1.02-2.41). The use of the NRTIs DDI or D4T was also found to increase the hazards of regimen discontinuation when compared to ABC or TDF use (HR 2.16, 95%CI 1.09-4.26). In this final model, time period of ART initiation remained non-significant, and regimen dosing frequency lost statistical significance. The only patient characteristic associated with regimen longevity in MV Cox PH analyses was affective mental health (MH) disorder, which increased the hazards of early regimen discontinuation across all three models ().
Table 2 Initial ARV regimen longevity as a function of patient characteristics, time period of ARV initiation, regimen complexity and antiretroviral regimen composition among antiretroviral-naïve patients starting initial ARV regimens at the UAB 1917 (more ...)
All-cause regimen discontinuation was greater in earlier regimens (1 January 2000-31 July 2004) relative to those used after August 2004 (14% vs. 6% at 90 days, 38% vs. 30% at 360 days). Among discontinued regimens, medication related toxicity was the most commonly cited reason, accounting for a greater proportion of discontinued regimens in the early vs. post-August 2004 time periods (80% vs. 62% at 90 days, 64% vs. 43% at 360 days) (Data not shown).