THE EFFICIENCY OF 48-WEEK TREATMENT WITH LOPINAVIR/RITONAVIR IN COMBINATION WITH LAMIVUDIN IN HIV-1-INFECTED PATIENTS IN THE ROUTINE CLINICAL SETTINGS OF THE RUSSIAN FEDERATION: RESULTS OF A PROSPECTIVE, MULTICENTER, OBSERVATIONAL STUDY (THE SIMPLE STUDY)

Objective. To evaluate the virologie efficiency of dual antiretroviral therapy (ART) [lopinavir/ritonavir (LPV/r) + lamivudine (3TC)] in treatment-experienced HIV-1-infected patients in the routine clinical settings of the Russian Federation. Subjects and methods. The multicenter non-interventional study was conducted in 13 federal and republican centers for prevention and control of AIDS and communicable diseases in 12 regions of the Russian Federation. The inclusion criteria were an age 18 years or older, plasma HIV-1 RNA < 50 copies/ml for at least 6 months on any triple ART of a total duration of at least 6 months; and clinically indicated switching to the LPV/r + 3TC regimen. The exclusion criteria were contraindications to the dual regimen or previous participation in this program. The patients received LPV/r + 3TC therapy according to their physician’s prescription and the local drug label at daily doses of 800/200 mg + 300 mg for 48 weeks. Data on HIV-1 viral load (VF) were collected at each visit. The primary endpoint was the proportion of patients on dual therapy with an undetectable HIV-1 RNA level at week 48. The secondary efficacy endpoints were the proportion of virologicaily suppressed patients at week 24, VL load and CD4+ T-cell counts at weeks 24 and 48. The safety assessment included HIV ART resistance testing, anthropometric measurements, blood chemistry evaluation, and the rates of serious and non-serious adverse events (AEs). The results were interpreted using descriptive statistics methods. Results. Between November 2015 and May 2017, the investigation enrolled 216 HIV-infected Caucasian male and female patients aged 20 to 69 years (mean age, 38.1 + 8.5 years; median age, 36.0 years); out of them, 202 (93.52%) patients completed the per-protocol study; 14 (6.48%) patients discontinued prematurely because of various reasons. The proportion of patients with an undetectable HIV-1 RNA level was 100% (95% Cl, 98.31-100.0) at Visit 1 (enrollment), 98.1 % (95% Cl, 95.17-99.48) at Visit 2 (week 12), 99.5%> (95% Cl, 9729-99.99) at Visit 3 (week 24), 100% (95% Cl, 98.21-100.0) at Visit 4 (week 36), and 100% (95% Cl, 98.18-100] at Visit 5 (week 48). At Visit 2 (week 12), VT + 50 copies/ml was recorded in 4 patients; in 2 of them, ineffective therapy (VT 3 400 copies/ml) was confirmed by repeated assays. One patient with a therapy failure was found to have a number of nucleoside and non-nucleoside reverse transcriptase inhibitor mutations. The СD4+ -lymphocyte cell counts increased significantly during ART versus at baseline; the mean week 48 increment in СD4+ -lymphocyte counts was 111.75 ± 184.48 cells/mm3(95% Cl, 86.15-137.34) or 1.43 ± 6.31% (95% Cl, 0.55-2.31). The patients well tolerated the TPV/r + 3TC regimen. There were no statistically significant changes in the mean anthropometric and laboratory values as compared to the baseline ones. Clinically significantly abnormal ATT, AST, blood glucose, and total cholesterol levels were recorded in 4 (1.9%) patients at weeks 24 and 48. The spontaneous reporting method showed that a total of 3 (1.4%) patients had 9 AEs. They all were non-serious and regarded by the attending physician as being unrelated to TPV/r + 3TC therapy. Six cases of AEs in 2 (1.9%) patients were related to gastrointestinal tract disorders (abdominal pain, diarrhea, dyspepsia, and vomiting); 3 (1.4%) patients terminated their participation in the study early due to pregnancy. Conclusion. Switching treatment-experienced HIV-1 infected patients to the TPV/r + 3TC regimen ensured maintenance of virologie suppression and improvement of an immune response during the 48-week follow-up. The proposed therapy regimen showed a good tolerance and a favorable safety prof ile.

HIV-1, dual therapy, lopinavir/ritonavir + lamivudine, previous treatment experience, viral load, antiretroviral drug resistance