The impact of second line antiretroviral treatment on viral load and immune status in patients with HIV/AIDS.
DOI:
https://doi.org/10.52692/1857-0011.2025.2-82.19Keywords:
HIV, AIDS, ART - antiretroviral treatment, adherence, viral load, CD4.Abstract
HIV/AIDS infection remains a major public health problem globally and in the Republic of Moldova. After treatment failure, switching to second-line ART is essential for infection control and immunological recovery. We aimed to evaluate the impact of second-line ART on viral load dynamics and immunological status in patients with HIV/AIDS who have failed first-line therapy. The retrospective-prospective study included a group of 101 HIV-positive patients, monitored during 2014-2020 at the “Toma Ciorbă” Clinical Hospital for Infectious Diseases in Chisinau. Diagnosis and surveillance were performed using serological and molecular genetic methods (PCR), and immunological status was assessed by flow cytometry. Clinical and laboratory parameters were monitored longitudinally, at the initiation of second-line ART and subsequently at 1, 2 and 3 years of treatment. The selection of therapeutic regimens was individualized, depending on comorbidities, adverse reactions and potential drug interactions. At the initiation of second-line ART, 59.4% of patients had severely compromised immunity (CD4˂200 cells/mcl), and 21.8% had extremely low levels (˂50 cells/mcl). Favorable virological response was observed in patients with good adherence, in whom 87,13% achieved undetectable viremia and a progressive increase in CD4 levels (100-150 cells/mcl/year) (46,5%, 95%CI(33,97-56,97), p<0,0001). In contrast, low- adherence patients showed high persistent viremia and a slow immunological evolution, associated with opportunistic infections (cerebral toxoplasmosis, pneumocystis jiroveci pneumonia, TB, esophageal candidiasis). The second-line ART has been shown to be effective in suppressing viral replication and improving immunological status, provided effective adherence. Constant monitoring and adaptation of therapeutic regimens are essential to prevent the development of ART resistance and improve prognosis in HIV/AIDS patients.
References
Jürgen Rockstroh JA. Ghidul eacs 12.0. 2023;165.
Huynh K, Vaqar S, Gulick PG. Hiv prevention. In treasure island (fl); 2025.
Fast-Track: ending the aids epidemic by 2030 [internet]. Unaids. 2014. Available from: unaids.org
UNAIDS. Fact sheet 2024, global hiv statistics. 2025;1–7. Available from: https://www.unaids.org/en/ resources/fact-sheet
Swinkels HM, vaillant aaj, nguyen ad, gulick pg. Hiv and aids. Geriatr gastroenterol [internet]. 2024 Jul 27 [cited 2025 Mar 23];659–66. Available from: https://www. ncbi.nlm.nih.gov/books/NBK534860/
Global HIV/AIDS Overview | hiv.gov [internet]. [cited 2025 Jul 12]. Available from: https://www.hiv. gov/federal-response/pepfar-global-aids/global-hiv-aids- overview
Plăcintă G, Curocichin G, Anatolie Vișnevschi, Nicolae B, Guțu D. Protocol clinic național (ediția a iii-a), profilaxia pre- expunere la infecția hiv. In chișinău: ministerul sănătății; 2025. p. 7–8.
Gidey K, Mache A, Hailu BY, Asgedom SW, Tassew SG, Nirayo YL. Second-line antiretroviral treatment outcomes and predictors in tigray region, ethiopia. Infect drug resist. 2023;16(July):4903–12.
Rohr JK, Ive P, Robert Horsburgh C, Berhanu R, Shearer K, Maskew M, et al. Marginal structural models to assess delays in second-line hiv treatment initiation in south africa. Plos one. 2016 Aug 1;11(8).
Ssempijja V, Nakigozi G, Chang L, Gray R, Wawer M, Ndyanabo A, et al. Rates of switching to second- line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among hiv-infected adults with virologic failure in rakai, uganda. Bmc infect dis [internet]. 2017 Aug 22 [cited 2025 Jul 18];17(1). Available from: https://pubmed.ncbi.nlm.nih. gov/28830382/
Zealiyas K, Gebreegziabxier A, Getaneh Y, Kidane E, Woldesemayat B, Yizengaw A, et al. Viral suppression and hiv drug resistance among patients on second-line antiretroviral therapy in selected health facility in ethiopia. Viruses 2025, Vol 17, Page 206 [Internet]. 2025 Jan 31 [cited 2025 Jul 18];17(2):206. Available from: https://www.mdpi.com/1999-4915/17/2/206/htm
BernabCrossed D Sign© KJ, Siedner M, Tsai AC, Marconi VC, Murphy RA. Detection of hiv virologic failure and switch to second-line therapy: a systematic review and meta-analysis of data from sub-saharan africa. Open forum infect dis [internet]. 2022 May 1 [cited 2025 Jul 18];9(5). Available from: https://pubmed.ncbi.nlm.nih. gov/35434173/
Mwavika ET, Kunambi PP, Masasi SJ, Lema N, Kamori D, Matee M. Prevalence, rate, and predictors of virologic failure among adult hiv-infected clients on second-line antiretroviral therapy (art) in tanzania (2018–2020): a retrospective cohort study. Bull natl res cent 2024 481 [internet]. 2024 Oct 1 [cited 2025 Jul 18];48(1):1–13. Available from: https://bnrc.springeropen. com/articles/10.1186/s42269-024-01248-5
Sivamalar S, Dinesha TR, Gomathi S, Pradeep A, Boobalan J, Solomon SS, et al. Accumulation of hiv- 1 drug resistance mutations after first-line immunological failure to evaluate the options of recycling nrti drugs in second-line treatment: a study from south india. Aids res hum retroviruses [internet]. 2017 Mar 1 [cited 2025 Jul 18];33(3):271–4. Available from: /doi/pdf/10.1089/ aid.2016.0070?download=true
Obasa AE, Mikasi SG, Brado D, Cloete R, Singh K, Neogi U, et al. Drug resistance mutations against protease, reverse transcriptase and integrase inhibitors in people living with hiv-1 receiving boosted protease inhibitors in south africa. Front microbiol [internet]. 2020 Mar 20 [cited 2025 Jul 18];11:509803. Available from: www.frontiersin.org
Hadaye RS, Jambhale VB, Shastri S. Assessment of adherence and factors contributing to non-adherence among patients on anti-retroviral therapy in a tertiary care hospital: a cross sectional study. J fam med prim care [internet]. 2020 [cited 2025 Apr 13];9(4):1921. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7346934/
Makwaga O, Adhiambo M, Mulama DH, Muoma J, Adungo F, Wanjiku H, et al. Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in busia county, kenya. Pamj 2020; 37:311 [Internet]. 2020 Dec 3 [cited 2025 Jul 18];37(311):311. Available from: https://www.panafrican- med-journal.com//content/article/37/311/full
Azijn H, Tirry I, Vingerhoets J, De Béthune MP, Kraus G, Boven K, et al. Tmc278, a next-generation nonnucleoside reverse transcriptase inhibitor (nnrti), active against wild-type and nnrti-resistant hiv-1. Antimicrob agents chemother. 2010 Feb;54(2):718–27.
Moore DM, Nanfuka M, Zhang W, Okoboi S, Kaleebu P, Kapaata A, et al. Limited impact of first-line drug resistance mutations on virologic response among patients receiving second-line antiretroviral therapy in rural uganda. J acquir immune defic syndr [internet]. 2023 Jan 1 [cited 2025 Jul 18];92(1):84–8. Available from: https://pubmed.ncbi.nlm.nih.gov/36150042/
Ryom L, De Miguel R, Cotter AG, Podlekareva D, Beguelin C, Waalewijn H, et al. Major revision version
0 of the european aids clinical society guidelines 2021. Hiv med. 2022 Sep;23(8):849–58.
Gandhi RT, Bedimo R, Hoy JF, Landovitz RJ, Smith DM, Eaton EF, et al. Antiretroviral drugs for treatment and prevention of hiv infection in adults: 2022 recommendations of the international antiviral society- usa panel. Jama [internet]. 2023 Jan 3 [cited 2025 Apr 13];329(1):63–84. Available from: https://pubmed.ncbi.nlm.nih.gov/36454551/
Holban T, Bîstrițchi I, Oltu I, Climașevschi I. Infecţia cu hiv la adult și adolescent. Protocol clinic național (ediția iii) pcn – 211. 2022.
Holban T, Bîstrițchi I, Oltu I, Climașevschi I, Popovici S, Condrat I. Pcn - 211. Infecţia cu hiv la adult şi adolescent. Protocol clinic național. 2018, editor. Chișinau; 2018. 22–27 p.
Micșanschi P, Bîstrițchi I, Cojocaru S, Climașevschi I, Spînu C, Holban T. Eșecul terapeutic și eficacitatea tratamentului antiretroviral de linia ii la pacienții hiv infectați din. In Chișinau; 2017. p. 205–9. Available from: http://repository.usmf.md/handle/20.500.12710/5411
Bîstrițchi I, Holban T, Micșanschi P. Tratamentul antiretroviral în infectia hiv/sida (compendiu pentru studenti si rezidenti). 18th–22nd ed. Chișinau; 2019. 18–22 p.
Engler K, Lènàrt A, Lessard D, Toupin I, Lebouché B. Barriers to antiretroviral therapy adherence in developed countries: a qualitative synthesis to develop a conceptual framework for a new patient-reported outcome measure. Aids care. 2018;30(sup1):17–28.
Boender TS, Sigaloff KCE, McMahon JH, Kiertiburanakul S, Jordan MR, Barcarolo J, et al. Long- term virological outcomes of first-line antiretroviral therapy for hiv-1 in low- and middle-income countries: a systematic review and meta-analysis. Clin infect dis an off publ infect dis soc am. 2015 Nov;61(9):1453–61.
Tao Y, Xiao X, Zhang C, Xie Y, Wang H. Prevalence of delayed antiretroviral therapy initiation among people living with hiv: a systematic review and meta-analysis. Plos one. 2023;18(10):e0286476.
World Health Organization. Consolidated guidelines on hiv prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach [internet]. World health organization; 2021 [cited 2025 Mar 23]. Available from: https://www.who.int/publications/i/item/9789240031593
Hamers RL, Rinke de Wit TF, Holmes CB. Hiv drug resistance in low-income and middle-income countries. Lancet hiv [internet]. 2018 Oct 1 [cited 2025 Mar 23];5(10):e588–96. Available from: https://www.thelancet.com/action/showFullText?pii=S2352301818301735
Baggaley RF, Irvine MA, Leber W, Cambiano V, Figueroa J, McMullen H, et al. Cost-effectiveness of screening for hiv in primary care: a health economics modelling analysis. Lancet hiv. 2017 Oct;4(10):e465–74.
SeyedAlinaghi S, Afsahi AM, Moradi A, Parmoon Z, Habibi P, Mirzapour P, et al. Current art, determinants for virologic failure and implications for hiv drug resistance: an umbrella review. Aids res ther. 2023 Oct;20(1):74.
Ndahimana J d’Amour, Riedel DJ, Mwumvaneza M, Sebuhoro D, Uwimbabazi JC, Kubwimana M, et al. Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in rwanda. Trop med int health. 2016 Jul;21(7):928– 35.
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