Impact of antiretroviral dosing frequency and daily pill burden on virological success rates in patients of the ICoNA cohort starting their first ART

Abstract

Complexity of antiretroviral treatment (ART) is a reason for non-adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low-pills QD [lpQD]); 3–6 daily pills QD (high-pills QD [hpQD]); 2–5 daily pills BID (low-pills BID [lpBID]); >6 daily pills BID (high-pills BID [hpBID]). VS was the date of first HIV RNA <50 cp/ml. Follow-up was censored at the date of VS or last available HIV RNA. Kaplan-Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44); HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre-ART CD4 and log HIV-RNA were 271/mm³ (range, 0–1672) and 4.84 cp/ml (1.70–6.38), respectively. Regimens were started in ‘00–‘02 24%,‘03–‘05 17%,‘06–‘08 17%,‘09–‘12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8). Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan-Meier curves are shown (Figure).

After stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre-cART CD4 and HIV-RNA, type of regimen a significantly reduced likelihood of achieving VS was found for ART complexity (hpQD: HR 0.76 95% CI 60–0.96; lpBID: 0.74, 0.59–0.94) when compared with lpQD. The chance of VS was higher in people starting ART more recently (RH 1.28 [95% CI 1.09–1.51] for ‘03–‘05; RH 1.64 [1.27–2.10] for ‘09–‘12; vs. ‘00–‘02) and was lower in people with previous AIDS (RH 0.85 [0.73–0.98]). Once-a-day dosing of ART, especially when combined with low daily pill burden, seems to be one of main factors contributing to the higher rate of success of ART in recent years.