ABSTRACT
OBJECTIVES: The single-tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. METHODS: We conducted two distinct randomized, double-blind, active-controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV-1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV-1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96. RESULTS: We randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) -4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI -4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment-emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001). CONCLUSIONS: Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment-emergent resistance.
Subject(s)
Anti-Retroviral Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Drug Combinations , Drug Substitution/methods , HIV Infections/drug therapy , Adult , Anti-Retroviral Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Double-Blind Method , Drug Substitution/adverse effects , Female , HIV-1/isolation & purification , Humans , Male , Middle Aged , RNA, Viral/blood , Treatment Outcome , Viral LoadABSTRACT
The N-terminal amino acid sequences of early and late pools of anti-DNP and anti-DNP-p-aminobenzoylglutamate (DNP-ABG) antibody light chains were quantitatively determined and compared. The amino acid composition at each locus of the N-terminal 20 amino acid residues of each light chain preparation was determined using automatic sequencing techniques coupled with high-pressure liquid chromatography and mass spectrometry. The sequence data obtained for the light chains corresponding to antibodies isolated early in the immune response (3-4 weeks) were essentially the same as those for light chains from antibodies isolated late in the response (12-14 weeks). In addition, it was observed that the sequence data obtained for the anti-DNP antibody light chain preparation were almost identical to those found for two anti-DNP-ABG antibody light "hain preparations. The sequence data obtained in the present study were compared with those obtained for normal rabbit light chains and with the composite sequence data published for other rabbit anti-hapten light chains.
