OUTCOMES OF SEVERELY ILL AIDS PATIENTS TREATED WITH EFAVIRENZ OR DOLUTEGRAVIR : A MULTICENTER, OBSERVATIONAL STUDYts

Description

Background – Currently, integrase inhibitors (INI) compose the preferred initial therapy for AIDS patients. There is scarce information on DTG use in late-presenters people living with HIV (PLHIV) patients. Objectives – To compare the effect of DTG or EFV-based regimens on outcomes of patients with advanced AIDS. Methods - We compared two cohort of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/ml) starting therapy with DTG (2018 to 2021, prospective cohort) or EFV-based regimens (2013 to 2016, retrospective cohort) from 5 Brazilian cities. Main endpoints were early (all cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count and changes in initial therapy (any reason). Results - We included all eligible patients in a consecutive way (both groups) until reaching 92 individuals per arm. Median baseline CD4 count (20 vs 21 cells/ml), and median HIV plasma viral load (5.5 copies/ml log10) were identical across groups. Viral suppression rates were higher in DTG than in EFV group at 24 (67.4% vs 42.4%,) and at 48 weeks (65.2% vs 45.7%, p<0.001 for both comparisons). More patients in DTG than in EFV group presented with CD4 >200 cells/ml, at 48 weeks (45% vs. 29%, p=0.03). Treatment changes (ITT, M=F) were significantly more frequent in EFV group (1% vs. 17%, p<0.0001). Relative mortality rate was 25% lower in DTG groups, but without statistical significance. Conclusions - DTG was more effective than EFV for treatment of severely illadvanced AIDS patients, with a higher rate of virological suppression and, higher durability, and lower mortality.

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Study design and participants: this observational, ambispective cohort included patients starting cART from 5 large Brazilian cities (Salvador, Natal, Manaus, Florianópolis and Porto Alegre). All sites were main public, referral centers for AIDS care, with well-trained health care professionals in HIV management. Clinical and laboratory data were recorded at baseline, 24 and 48 weeks after enrollment. Data collected during unsolicited visits due to the onset of adverse events, change of therapy or other outcome of interest were also recorded. Inclusion criteria ART-naïve patients starting ART from 2018 and 2020 were included, if they had a HIV-1 RNA plasma viral load >1,000 copies/ml, a WHO clinical stage 4, a baseline CD4 count below 50 cells/mm3, and were aged at least 18 years at enrollment. They started a lamivudine/tenofovir (fixed dose combination) plus DTG regimen. A second, retrospective cohort, was used for comparison purpose. It included patients with a similar profile who started therapy from 2013 to 2016, at each site, with a fixed-dose combination of lamivudine plus tenofovir and EFV. Data from retrospective cohort were obtained by review of medical charts. Either DTG or EFV regimens were the recommended therapy for ART-naïve patients, according to the Brazilian guidelines for antiretroviral therapy at the two study´s periods, respectively. Patients in both groups were included in a consecutive way, starting by the first eligible subjects attended during the study period, until the sample be completed. Procedures: We documented the number and causes of deaths during the study period. The main outcome for comparison was early mortality rates, defined as all-cause mortality at 1 year from ART start and any cause of interruption of therapy including death, changing ART, and lost to FU. Secondary main outcome was proportion of patients with plasma HIV-1 RNA loads (VL) of less than 50 copies per mL, at week 48. Virological failure was defined as a VL>200 copies/mL. Further secondary outcomes at week 48 were changes in CD4 cells count (proportion of patients reaching a CD4 count higher than 200 cells per mL) and proportion of patients changing initial therapy, for any reason. Baseline date was defined as the date patients started ART. HIV route of transmission was categorized as persons who inject drugs (PWID); men who have sex with men (MSM); occupational exposure; and persons whose only self-reported risk was heterosexual contact. The predictor variables were sex, age, baseline CD4 cells count, and HIV-1 RNA plasma VL. Additional laboratory variables included white blood cells, hemoglobin, platelets, liver enzymes, creatinine, fasting glucose, and serum lipids (fasting total cholesterol, LDL, HDL, triglycerides). All laboratory tests were performed at baseline, 24 and 48 weeks.

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