Comparative evaluation of the applicability of fixed-dose combined drugs in HIV therapy / Avaliação comparativa da aplicabilidade de drogas combinadas em dose fixa na terapia do HIV
DOI:
https://doi.org/10.34119/bjhrv4n6-429Keywords:
acquired immunodeficiency syndrome, aids, human immunodeficiency virus, antiretroviral, fixed-dose combination.Abstract
The principal global pandemic is Acquired Immunodeficiency Syndrome (AIDS), the early diagnosis and the premature treatment is the main current strategies in combating the development and spread of the disease. Antiretroviral therapy is effective and safe, what is sought nowadays is compliance and convenience for the patient. Different countries adopt different combinations of antiretroviral drugs when using the fixed-dose combination (FDC). The study design was a meta-analysis with clinical trials, patients experienced and naïve of treatment. The Pubmed, Scopus, Embase, Web of Science and Cochrane databases were searched for studies reporting AIDS treatment. The primary outcome was viral load and another outcome is adverse events. The results of the main analysis included 5224 patients. Since there was significant heterogeneity between studies, random effects were selected, and they showed an event rate of 0.67 (95%CI from 0.57 to 0.77). The exploratory analysis showed the general drug effects are not consistently significant along time, and treatments of longer times are more efficient. Specifically, the random analyses of 6 months and 1 year did not show significant drug effects on viral load, while a significant effect of 71% (95% CI from 0.61 to 0.80) in a very heterogeneous analyses (I2>96%). First, d4T-3TC-NVP showed a mean rate of only 21% efficacy and the second, EFV-TDF-FTC did not reach statistical significance (p=0.07). This meta-analysis shows that fixed-dose combination therapy is tolerability, safety and effective, occurred viral load suppression between patients on FDC.
References
World Health Organization. WHO Health Topics [Internet]. Who. 2021. Available from: https://www.who.int/health-topics/leishmaniasis#tab=tab_1
Drain PK, Dorward J, Violette LR, Quame-Amaglo J, Thomas KK, Samsunder N, et al. Point-of-care HIV viral load testing combined with task shifting to improve treatment outcomes (STREAM): findings from an open-label, non-inferiority, randomised controlled trial. Lancet HIV. 2020;7(4).
Yoo-Jeong M, Schnall R. Accuracy of Self-Reports of HIV Viral Load Status and Risk Factors for Inaccurate Reporting of Viral Suppression among Racial/Ethnic Minority Persons Living with HIV. Vol. 34, AIDS Patient Care and STDs. 2020.
UNAIDS. Public Health and Viral Load Suppression [Internet]. Undetectable = Untransmittable : 2018. Available from: https://www.unaids.org/en/resources/presscentre/featurestories/2018/july/undetectable-untransmittable
World Health Organisation (WHO). Policy Brief: Update of Recommendations on First-and Second-Line Antiretroviral Regimens. WHO Libr Cat Data. 2019;(July).
Clay PG, Nag S, Graham CM, Narayanan S. Meta-Analysis of studies comparing single and multi-Tablet fixed dose combination HIV treatment regimens. Vol. 94, Medicine (United States). 2015.
Endalamaw A, Mekonnen M, Geremew D, Yehualashet FA, Tesera H, Habtewold TD. HIV/AIDS treatment failure and associated factors in Ethiopia: Meta-analysis. BMC Public Health. 2020;20(1).
Sri Dharma Astiti CI, Sagung Sawitri A., Parwati T. Factors associated to first line antiretroviral therapy (ART) failure among HIV/AIDS patients at Sanglah Hospital, Bali. Public Heal Prev Med Arch. 2017;
Elnaem MH, Irwan NA, Abubakar U, Sulaiman SAS, Elrggal ME, Cheema E. Impact of medication regimen simplification on medication adherence and clinical outcomes in patients with long-term medical conditions. Vol. 14, Patient Preference and Adherence. 2020.
Gebrezgabher BB, Kebede Y, Kindie M, Tetemke D, Abay M, Gelaw YA. Determinants to antiretroviral treatment non-adherence among adult HIV/AIDS patients in northern Ethiopia. AIDS Res Ther. 2017;14(1).
Al Tall YR, Mukattash TL, Sheikha H, Jarab AS, Nusair MB, Abu-Farha RK. An assessment of HIV patient’s adherence to treatment and need for pharmaceutical care in Jordan. Int J Clin Pract. 2020;74(7).
Gerenutti M, Martinez AMV, Bergamaschi C de C. The effectiveness of a pharmaceutical care model on adherence to antiretroviral therapy: A same-based cohort study in Brazil. Adv Pharm Bull. 2017;7(3).
Molino CGRC, Carnevale RC, Rodrigues AT, Moriel P, Mazzola PG. HIV pharmaceutical care in primary healthcare: Improvement in CD4 count and reduction in drug-related problems. Saudi Pharm J. 2017;25(5).
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1).
Moher D, Liberati A, Tetzlaff J AD. PRISMA 2009 Flow Diagram. Vol. 6, The PRISMA statement. 2009.
GYAMFI PKTA, MENSAH KB, ARHIN SM, MOOMIN A. HAART THERAPY IN GHANA: COMPARATIVE ASSESSMENT OF THE EFFECTIVENESS OF DIFFERENT HAART COMBINATIONS AT KOMFO ANOKYE TEACHING HOSPITAL. Int J Pharm Pharm Sci. 2020;
Puspitasari RA, Soelistijo SA, Hadi U. Effect of anti-retroviral fixed-dose combination tenofovir, lamivudine, and evafirenz on lipid profile in HIV/AIDS patients. Syst Rev Pharm. 2020;11(3).
O’Brien DP, Sauvageot D, Zachariah R, Humblet P. In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy. AIDS. 2006;20(15).
Pujari SN, Patel AK, Naik E, Patel KK, Dravid A, Patel JK, et al. Effectiveness of generic fixed-dose combinations of highly active antiretroviral therapy for treatment of HIV infection in India. J Acquir Immune Defic Syndr. 2004;37(5).
Taramasso L, Di Biagio A, Maggiolo F, Tavelli A, Lo Caputo S, Bonora S, et al. First-line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison. HIV Med. 2018;19(7).
Orkin C, Molina JM, Lombaard J, Dejesus E, Rodgers A, Kumar S, et al. Once-daily doravirine in human immunodeficiency virus type 1-infected, antiretroviral-naive adults: An integrated efficacy analysis. Clin Infect Dis. 2020;70(7).
Wiriyatanakorn S, Sungkanuparph S. Switching Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) to TDF/FTC/Rilpivirine vs Continuing TDF/FTC/EFV in HIV-Infected Patients with Virological Suppression: A Randomized Controlled Trial. Open Forum Infect Dis. 2019;6(7).
Hagins D, Dietz C, Jain M, Van Dam C, Brar I, Man C, et al. Efficacy of Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) Fixed-Dose Combination (FDC) Compared With Ritonavir-Boosted Atazanavir (ATV/r) Plus Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) in Treatment-Naive Women With Human Immunodeficiency Virus (HIV)-1 Infection (ARIA Study): Analyses by Race Subgroups. Open Forum Infect Dis. 2016;3(suppl_1).
Elzi L, Erb S, Furrer H, Ledergerber B, Cavassini M, Hirschel B, et al. Choice of initial combination antiretroviral therapy in individuals with HIV infection determinants and outcomes. Arch Intern Med. 2012;172(17).
Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835).
Duse AG, Morar A, Landman I, Vermaak WJH, Schoeman H, Kruger MJ, et al. Short-term effectiveness and safety of HAART in the form of a generic fixed-dose combination of stavudine, lamivudine and nevirapine (Triviro) in HIV-1-infected adults in Zimbabwe. South Afr J HIV Med. 2008;(30).
Natu SA, Daga SR. Antiretroviral therapy in children: Indian experience. Indian Pediatr. 2007;44(5).
Calmy A, Pinoges L, Szumilin E, Zachariah R, Ford N, Ferradini L. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: Multicentric observational cohort. AIDS. 2006;20(8).
Moodley T, Moodley D, Sebitloane M, Maharaj N, Sartorius B. Improved pregnancy outcomes with increasing antiretroviral coverage in South Africa. BMC Pregnancy Childbirth. 2016;16(1).
Susilo D, Wibisono S, Hadi U. TSH, FT4, and CD4 profile in HIV/AIDS patients before and after antiretroviral fixed-dose combination tenofovir, lamivudine, evafirenz therapy. Syst Rev Pharm. 2020;11(3).
Squires K, Bekker LG, Katlama C, Yazdanpanah Y, Zhou Y, Rodgers AJ, et al. Influence of sex/gender and race on responses to raltegravir combined with tenofovir-emtricitabine in treatment-naive human immunodeficiency virus-1 infected patients: Pooled analyses of the STARTMRK and QDMRK studies. Open Forum Infect Dis. 2017;4(1).
De Los Santos I, Gómez-Berrocal A, Valencia E, Asensi V, Gijón P, Moreno V, et al. Efficacy and tolerability of Darunavir/Ritonavir in combination with abacavir/lamivudine: An option in selected HIV-infected patients. HIV Clin Trials. 2013;14(5).
Oyugi JH, Byakika-Tusiime J, Ragland K, Laeyendecker O, Mugerwa R, Kityo C, et al. Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda. AIDS. 2007;21(8).
Bourgeois A, Laurent C, Mougnutou R, Nkoué N, Lactuock B, Ciaffi L, et al. Field assessment of generic antiretroviral drugs: A prospective cohort study in Cameroon. Antivir Ther. 2005;10(2).
Manosuthi W, Sungkanuparph S, Tansuphaswadikul S, Prasithsirikul W, Athichathanabadi C, Likanonsakul S, et al. Effectiveness and metabolic complications after 96 weeks of a generic fixed-dose combination of stavudine, lamivudine, and nevirapine among antiretroviral-naive advanced HIV-infected patients in Thailand: A prospective study. Curr Ther Res - Clin Exp. 2008;69(1).
Rockstroh JK, Dejesus E, Lennox JL, Yazdanpanah Y, Saag MS, Wan H, et al. Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: Final 5-year results from STARTMRK. J Acquir Immune Defic Syndr. 2013;63(1).
Rossi MC, Inojosa WO, Battistella G, Carniato A, Farina F, Giobbia M, et al. Desimplification to multi-tablet antiretroviral regimens in human immunodeficiency virus-type 1 infected adults: A cohort study. World J Clin Cases. 2019;7(14).
Kapadia SN, Grant RR, German SB, Singh B, Davidow AL, Swaminathan S, et al. HIV virologic response better with single-tablet once daily regimens compared to multiple-tablet daily regimens. SAGE Open Med. 2018;6.
Manosuthi W, Chimsuntorn S, Likanonsakul S, Sungkanuparph S. Safety and efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine antiretroviral therapy between HIV-infected patients with baseline CD4 <50 versus CD4 ≥ 50 cells/mm3. AIDS Res Ther. 2007;4.
Li X, Brown TT, Ho KS, Witt MD, Phair J, Jacobson LP. Recent Trends and Effectiveness of Antiretroviral Regimens among Men Who Have Sex with Men Living with HIV in the United States: The Multicenter AIDS Cohort Study (MACS) 2008-2017. Open Forum Infect Dis. 2019;6(9).
Kakuda TN, Opsomer M, Timmers M, Iterbeke K, Van De Casteele T, Hillewaert V, et al. Pharmacokinetics of darunavir in fixed-dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers. J Clin Pharmacol. 2014;54(8).
German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Syndr. 2010;55(3).
Triyono EA, Seran SR, Hasmono D. Profile of antiretroviral and its outcome on patients with HIV-AIDS in Wamena Public Hospital. Dermatology Reports. 2019;11(S1).
Mukherjee A, Singla M, Velpandian T, Sirohiwal A, Vajpayee M, Singh R, et al. Pharmacokinetics of nevirapine, stavudine and lamivudine in Indian HIV-infected children receiving generic fixed dose combinations. Indian Pediatr. 2014;51(3).
