Off-label rilpivirine in combination with emtricitabine and tenofovir may help reduce out-of-pocket spending for patients with HIV.
Single-tablet regimens (STR) have been associated with high adherence rates and improved quality of life in adults with HIV-1.
With this knowledge, a recent study tested the safety and efficacy of off-label rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily, single-table regiment (STR) in children and adolescents with HIV-1 to determine whether this strategy can improve adherence.
A multicenter, observational study published in Medicine included 17 vertically HIV-1 infected children and adolescents (<18 years) from 6 pediatric reference hospitals (Cohort of the Spanish Pediatric HIV Network, CoRISpe).
Participants were administered STR with RPV/FTC/TDF under the Spanish off-label medication use program, and were monitored from baseline from March 2013 through June 30, 2015, discontinuation, or failure to follow-up.
Adherence was evaluated by pill count, assessing the dose taken, interviewing parents or guardians, and was summarized as a single percentage for each combined antiretroviral therapy (cART) regimen for each patient. Adherence was categorized as poor (<70%), intermediate (70—90%), good (91–99%), or perfect (100%).
Resistance to RPV/FTC/TDF was defined using major mutations from the IAS-USA mutation list of 2013. Plasma VL (HIV-1 RNA) was measured by Amplicor Monitor assay and real-time NASBA with a detect limit of 20 HIV-1 RNA copies/mL. Virological failure was defined as the inability to achieve or maintain suppression of viral replication below 20 copies/mL and CD4 was quantified by flow cytometry.
Researchers monitored toxicity, including renal toxicity, hepatic toxicity, lipid profile cholesterol, and glucose every 6 months during the follow-up.
Participants ranged from 11- to 16.7-years-old, and at the start of enrollment there were 7 participants who had moderate immunosuppression and 2 who had a clinical stage C. At baseline, all participants showed HIV-1 RNA <10,000 copies/mL.
Reasons for RPV/FTC/TDF initiation were simplification (n=4; 24%); toxicities (neurological, associated with EFV, n=2, 12%; dyslipidemia, n-2, 12%); viral failure (n=8; 47%); and CD4 count below 350/μL in the naïve patient.
For RPV-based treatment, the overall median time was 61.9 weeks (IQR: 41.1-90.5). In the undetectable viral load (uVL) and detectable viral load (dVL) groups, the median time on RPV-based treatment was 89.1 weeks (IQR: 66.5-100.9) and 39.6 weeks (IQR: 23.6-55.4), respectively.
The results of the study found that 7 of the 8 adolescents with uVL at baseline, which included the 3 patients with RAMs, maintained uVL for a median time of 93.6 weeks (IQR: 87.4-104.3). Only one participant, a 17-year-old male, developed viral failure because of poor adherence (<10%) caused by antisocial personality disorder.
In the dVL group, 8 out of 9 patients achieved and maintained uVL for a total median time of 41.1 weeks. However, 1 participant experienced a hiccup at the end of the follow-up because of intermediate adherence (50-90%).
One adolescent remained persistently detectable during the study due to low adherence and low level TDF resistance (T215Y), while a patient with T215Y and Y181C mutations was able to reach a viral load below 100 copies/mL after 30.9 weeks. The median CD4 counts and the CD4/CD8 ratio improved in both groups, and there was a significant difference observed when analyzing the whole group (P=0.01 and P=0.01, respectively).
Five patients changed their immunological category from moderate immunosuppression to no suppression, and 1 patient moved from category 1 to 2. Regarding adverse events (AEs), none of the patients discontinued therapy, but 3 patients reported grade 1 AEs.
Two adolescent patients saw an increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), but for 1 of the patients, this was not deemed to be related to RPV-based therapy. One patient saw an elevation in triglycerides.
Although lipid profile did improve in the uVL group, it did not reach statistical significance. In the dVL group, cholesterol improved significantly. Clinical AEs, such as skin rash or central nervous system-related symptoms related to RPV/FTC/TDF were not found during follow-up.
Two adolescents who suffered from insomnia and abnormal dreams on their previous EFV-based regimen reported no complaints with the new cART. One adolescent with poor adherence ended up discontinuing the RPV-based regimen and dropped out of care. There were no reported deaths in the study.
The findings revealed that RPV/FTC/TDF was associated with control of viral replication, improved CD4 counts and CD4/CD8 ratio, as well as serum lipid profiles. Only low-grade AEs were reported during clinical follow-up.
Two limitations to the study were the small sample size and the different follow-up times between the groups. However, authors noted that there are limited data on adolescent patients and no data on children who receive RPV/FTC/TDF therapy, so the findings are likely to be useful.
Authors stated that larger, prospective clinical studies will need to be conducted to confirm their findings.