Late treatment failures in cerebrospinal fluid in patients on long-term maintenance ART with ritonavir-boosted protease PI monotherapy.

BACKGROUND: Antiretroviral treatment (ART) with ritonavir-boosted protease inhibitor monotherapy (rb-PMT) remains a potentially attractive strategy for treatment simplification in HIV-infected individuals. However, long-term follow-up in particular with respect to HIV-RNA suppression in cerebrospinal fluids (CSF) is still lacking. METHODS: Patients who participated in one of the three monotherapy trials [indinavir/r, ATARITMO (atazanavir/r), MOST (lopinavir/r)] at our HIV clinic and remained successfully suppressed during the entire trial (plasma < 50 copies/mL, CSF < 100 copies/mL) were offered to continue their monotherapy under close monitoring. While on rb-PMT, patients were asked to provide CSF samples in yearly or 2-yearly intervals. All patients fully suppressed in plasma and CSF for at least 12 months were included in the analysis. Patients demonstrating any failure in plasma or CSF resumed triple combined ART. RESULTS: A total of 27 patients (5 women and 22 men) fulfilled the entry criteria. The median follow-up time was 4.8 (1.1-10.9) years with an overall experience of 139 patient-years on monotherapy. Eleven of 27 (41 %) patients (2 women and 9 men) developed virologic failure (1 in plasma only, 4 in CSF only, 4 both in plasma and CSF and 2 in plasma with CSF not available). Plasma failure occurred in 7 patients after a median follow-up of 25 (13-32) months, and CSF failure in 8 patients after a median follow-up of 30 (14-64) months. Seven patients are still on rb-PMT with atazanavir/r. Failure was associated with shorter duration of fully suppressed plasma viral load prior to starting (p < 0.022). CONCLUSION: For selected patients, rb-PMT might be a valid long-term treatment strategy. Nevertheless, even after 12 months of full HIV-RNA suppression, more than 1/3 of patients may still develop failure in either plasma or CSF. Given the observation of isolated CSF failure, treatment monitoring with regular lumbar puncture should be recommended in rb-PMT. Only monotherapy with atazanavir/r was successful beyond 39 months. Monotherapy failure was significantly associated with a shorter duration of complete HIV-RNA suppression in plasma prior to rb-PMT start. Further investigation is needed to better identify predictors for patients that will qualify for successful long-term rb-PMT.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.