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      Brief Report: Virologic Impact of the Dolutegravir Transition: Prospective Results From the Multinational African Cohort Study

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          Background:

          The real-world impact on viral suppression of switching from non–dolutegravir-based therapy to tenofovir/lamivudine/dolutegravir (TLD) is not thoroughly characterized in Africa. We described the virologic consequences of switching regimens in the African Cohort Study (AFRICOS), an observational cohort in Nigeria, Kenya, Uganda, and Tanzania.

          Methods:

          Among antiretroviral-experienced people living with HIV (PLWH) in AFRICOS, we compared viral load (VL) nonsuppression (VL ≥ 1000 copies/mL) among those who switched with those who never switched to TLD, restricting to participants who had at least 1 visit with a recorded VL after the countrywide rollout of TLD. We calculated Kaplan–Meier curves and conducted Cox proportional hazards modeling to estimate adjusted hazard ratios and 95% confidence intervals for factors potentially associated with nonsuppression.

          Results:

          As of September 1, 2021, there were 3108 PLWH enrolled. Among 1576 participants who switched to TLD, 1486 (94.3%) remained suppressed after transition, 12 (0.8%) remained unsuppressed, and 38 (2.4%) lost suppression, compared with 652 (82.1%), 75 (9.4%), and 46 (5.8%), respectively, of 797 participants who did not switch ( P < 0.001). After adjustment for sex, age, study site, and self-reported antiretroviral therapy adherence, virally suppressed participants who did not switch to TLD had significantly higher rates of losing viral suppression compared with those who switched (adjusted hazard ratio: 4.26; 95% confidence interval: 2.72 to 6.68).

          Conclusions:

          PLWH transitioning to TLD had higher rates of viral suppression compared with those who remained on other regimens. Even within a highly suppressed population, TLD transition provided significant benefits for achieving or maintaining viral suppression.

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          Most cited references17

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          Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

          Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015 .).
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            Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV

            Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries.
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              Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial

              Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed.
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                Author and article information

                Contributors
                Journal
                J Acquir Immune Defic Syndr
                J Acquir Immune Defic Syndr
                qai
                Journal of Acquired Immune Deficiency Syndromes (1999)
                JAIDS Journal of Acquired Immune Deficiency Syndromes
                1525-4135
                1944-7884
                1 November 2022
                18 August 2022
                : 91
                : 3
                : 285-289
                Affiliations
                [a ]US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD;
                [b ]Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD;
                [c ]Makerere University Walter Reed Project, Kampala, Uganda;
                [d ]US Army Medical Research Directorate—Africa, Kericho, Kenya;
                [e ]US Army Medical Research Directorate—Africa, Kisumu, Kenya;
                [f ]HJF Medical Research International, Kisumu, Kenya;
                [g ]HJF Medical Research International, Mbeya, Tanzania; and
                [h ]HJF Medical Research International, Abuja, Nigeria.
                Author notes
                Correspondence to: Allahna Esber, PhD, MSPH, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 400, Bethesda, MD 20817 (e-mail: aesber@ 123456global-id.org ).
                Author information
                https://orcid.org/0000-0001-5337-0126
                https://orcid.org/0000-0002-8026-9901
                Article
                QAIV22658 00009
                10.1097/QAI.0000000000003065
                9561234
                35980350
                0910f8f3-73f2-4b6b-9535-ac960548b157
                Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 14 March 2022
                : 20 June 2022
                Categories
                Clinical Science
                Custom metadata
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                dolutegravir,virologic response,hiv integrase inhibitors

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