HIV drug therapy duration; a Swedish real world nationwide cohort study on InfCareHIV 2009-2014

Abstract

BackgroundAs HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort.MethodsAdult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009–2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included. Dolutegravir was excluded due to short follow up period. Multivariate Cox proportional hazards models were used to estimate hazard ratios for treatment discontinuation.ResultsIn treatment-naïve 2541 patients started 2583 episodes of treatments with a 3rd agent. Efavirenz was most commonly used (n = 1096) followed by darunavir (n = 504), atazanavir (n = 386), lopinavir (n = 292), rilpivirine (n = 156) and raltegravir (n = 149). In comparison with efavirenz, patients on rilpivirine were least likely to discontinue treatment (adjusted HR 0.33; 95% CI 0.20–0.54, p<0.001), while patients on lopinavir were most likely to discontinue treatment (adjusted HR 2.80; 95% CI 2.30–3.40, p<0.001). Also raltegravir was associated with early treatment discontinuation (adjusted HR 1.47; 95% CI 1.12–1.92, p = 0.005). The adjusted HR for atazanavir and darunavir were not significantly different from efavirenz. In treatment-experienced 2991 patients started 4552 episodes of treatments with a 3rd agent. Darunavir was most commonly used (n = 1285), followed by atazanavir (n = 806), efavirenz (n = 694), raltegravir (n = 622), rilpivirine (n = 592), lopinavir (n = 291) and etravirine (n = 262). Compared to darunavir all other drugs except for rilpivirine (HR 0.66; 95% CI 0.52–0.83, p<0.001) had higher risk for discontinuation in the multivariate adjusted analyses; atazanavir (HR 1.71; 95% CI 1.48–1.97, p<0.001), efavirenz (HR 1.86; 95% CI 1.59–2.17, p<0.001), raltegravir (HR 1.35; 95% CI 1.15–1.58, p<0.001), lopinavir (HR 3.58; 95% CI 3.02–4.25, p<0.001) and etravirine (HR 1.61; 95% CI 1.31–1.98, p<0.001).Besides the 3rd agent chosen also certain baseline characteristics of patients were independently associated with differences in treatment duration. In naive patients, presence of an AIDS-defining diagnosis and the use of other backbone than TDF/FTC or ABC/3TC increased the risk for early treatment discontinuation. In treatment-experienced patients, detectable plasma viral load at the time of switch or being highly treatment experienced increased the risk for early treatment discontinuation.ConclusionsTreatment durability is dependent on several factors among others patient characteristics and ART guidelines. The choice of 3rd agent has a strong impact and significant differences between different drugs on treatment duration exist.

Long-term use of darunavir/ritonavir-containing regimens in daily practice in Belgium: retrospective observational cohort data of 1701 HIV-patients

“…No unexpected adverse events were reported and the good tolerability that was seen in previous clinical studies comparing DRV/r with LPV/r or the integrase inhibitors raltegravir and dolutegravir was confirmed [4,6,24]. This is in line with the Swedish InfCare study, where DRV/r was the most commonly used third agent for treatment-experienced patients and showed the lowest risk for treatment discontinuation [22].…”

“…~80% in PROTEA [20] and ~90% in MONET [21]), they only represent half of the patients (48.6%) in this cohort. Similar to the Swedish InfCare study [22], about one-third of the patients were of African ethnicity. More recently published clinical Figure 1.…”

Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV

“…Using EFV as a reference, the adjusted hazard ratio for discontinuation among treatment-naïve patients was 0.33 for RPV (confidence interval: 0.20-0.54, p < 0.001) and 1.47 for RAL (confidence interval: 1.12-1.92, p = 0.005). Thus, patients on RPV-containing treatments discontinued therapy less often than those on ETR or EFV [113], which is in agreement with the findings of the ECHO/THRIVE trials [47,52].…”

“…A study [113] with 2541 patients comparing RPV, ETR, EFV, RAL, lopinavir, ATV, and darunavir found that RPV had the lowest discontinuation rate, while RAL was associated with early discontinuation. After three treatment years, the discontinuation rate among treatment-experienced patients was 22% for RPV, 47% for ETR, and 41% for RAL.…”

First‐line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison

“…Previous analyses of durability have compared people receiving the two NNRTIs without accounting, in the study entry criteria, for the fact that RPV use is restricted to people with an untreated HIV RNA level < 100 000 copies/mL. This makes the interpretation of the comparisons even more difficult [19,20].…”