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      Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real‐life study in Brazil

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          Abstract

          Introduction

          The relative efficacy of different antiretroviral ( ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load ( VL) measurements at pre‐specified timepoints after ART onset. However, data from real‐life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil.

          Methods

          Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir‐boosted atazanavir (regimen 3)).

          Results and Discussion

          We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 ( p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12‐month cumulative viraemia. The model predicted a 45‐unit increase in log 10 copy‐days/ mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70‐unit increase in log 10 copy‐days/ mL cumulative viraemia for regimen 3 as compared with regimen 1 (95% CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir‐lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders.

          Conclusions

          Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

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          Most cited references 19

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          Differential impact of adherence on long-term treatment response among naive HIV-infected individuals.

          To examine the long-term impact of adherence on virologic, immunologic, and dual response stratified by type of HAART regimen in treatment-naive patients starting HAART in British Columbia, Canada; and to assess the degree of virologic and immunologic response associated with emergence of drug resistance, progression to AIDS, and mortality. Eligible participants initiated HAART between 1 January 2000 and 30 November 2004, were followed until 30 November 2005, and had at least 2 years of follow-up. Virologic and immunologic responses were dichotomized at their median values. Virologic response was defined as at least 65% of follow-up time with plasma viral load (pVL) of less than 50 copies/ml. Immunologic response was defined as a CD4 cell count increase of at least 145 cells/microl. Adherence measures were based on prescription refill compliance. Proportional odds models and logistic regression were used to address our objectives. The distribution of patient responses was 394 (44.9%) for CD4+/pVL+ (best), 350 (39.9%) for CD4-/pVL+ or CD4+/pVL- (incomplete), and 134 (15.3%) for CD4-/pVL- (worst). We found a positive correlation between adherence and virologic and immunologic responses (P < 0.01). Having worst compared with best response (reference group) was associated with higher odds of mortality (odds ratio: 6.09; 95% confidence interval: 2.57-14.42) and emergence of drug resistance (odds ratio: 10.56; 95% confidence interval: 5.93-18.81) even after adjusting for adherence and HAART regimen. Patients not attaining the best virologic and immunologic responses are at a high risk for emergence of drug resistance and mortality, and these responses are highly dependent on the adherence level and initial HAART regimen. Patients on protease inhibitor-single did worse no matter the adherence level.
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            Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis.

            New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients.
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              • Record: found
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              Is Open Access

              Dolutegravir – a review of the pharmacology, efficacy, and safety in the treatment of HIV

              Dolutegravir is the newest integrase strand transfer inhibitor to be approved for the treatment of human immunodeficiency virus (HIV) infection. Dolutegravir is equivalent or superior to existing treatment regimens in both treatment-naïve and treatment-experienced patients including those with previous raltegravir or elvitegravir failure. The consistent efficacy coupled with excellent tolerability and infrequent drug–drug interactions makes the co-formulation of dolutegravir with two nucleotide reverse-transcriptase inhibitors an attractive treatment option. This review summarizes the pharmacokinetics, adverse event profile, and efficacy of dolutegravir in the treatment of HIV.
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                Author and article information

                Contributors
                viviansilva87@gmail.com
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                19 November 2019
                November 2019
                : 22
                : 11 ( doiID: 10.1002/jia2.v22.11 )
                Affiliations
                [ 1 ] Department of Surveillance, Prevention and Control of STIs Ministry of Health of Brazil HIV/AIDS and Viral Hepatitis Brasilia Brazil
                [ 2 ] Tropical Medicine Foundation Heitor Vieira Dourado Manaus Brazil
                [ 3 ] Department of Infectious and Parasitic Diseases Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil
                Author notes
                [* ] Corresponding author: Vivian I Avelino‐Silva, Av. Dr. Eneas de Carvalho Aguiar, 470, Sao Paulo, SP, ZIP code 05403‐000, Brazil. Tel: +55 11 30618347. ( viviansilva87@ 123456gmail.com )
                Article
                JIA225397
                10.1002/jia2.25397
                6863473
                31743620
                © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 1, Tables: 2, Pages: 6, Words: 4320
                Product
                Funding
                Funded by: OPAS – Organização Panamericana de Saúde
                Categories
                Short Report
                Short Reports
                Custom metadata
                2.0
                jia225397
                November 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.2 mode:remove_FC converted:19.11.2019

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