A Literature Review on ARV Adherence, CD4 Count, and Menstrual Disorders in HIV-Infected Women
DOI:
https://doi.org/10.56294/saludcyt20251824Keywords:
HIV, Antiretroviral Therapy, CD4 Count, Menstrual Disorders, Stress, Medication Adherence, Women's Reproductive HealthAbstract
HIV/AIDS remains a critical global health challenge, with women of reproductive age constituting a significant proportion of the affected population. The interplay between antiretroviral therapy (ART) regimens, medication adherence, psychological stress levels, CD4 cell counts, and menstrual health is complex and multifaceted. This systematic review synthesizes findings from eight studies published between 2015 and 2025, exploring how different ART regimens, particularly Dolutegravir-based (DTG) versus Efavirenz-based (EFV) affect immunological and reproductive outcomes in women living with HIV. The review highlights that regimen type, adherence to medication, and psychological stress significantly mediate CD4 count fluctuations and menstrual disturbances, including irregular cycles and amenorrhea. Furthermore, CD4 count acts as a mediating variable in the relationship between ART, stress, and menstrual health. Evidence suggests that DTG regimens are associated with better immune profiles and fewer reproductive side effects, whereas stress and poor adherence exacerbate immunosuppression and reproductive dysfunction. These findings underscore the need for integrated, gender-sensitive healthcare approaches that address immunological, psychological, and reproductive health in women with HIV.
References
1. United Nations Programme on HIV/AIDS. UNAIDS data 2021. Unaids. 2021. https://www.unaids.org/sites/default/files/media_asset/JC3032_AIDS_Data_book_2021_En.pdf
2. Moran JA, Turner SR, Marsden MD. Contribution of Sex Differences to HIV Immunology, Pathogenesis, and Cure Approaches. Front Immunol. 2022;13(May):1–8. https://doi.org/10.3389/fimmu.2022.905773.
3. Kementerian Kesehatan Republik Indonesia. Rencana Aksi Nasional Pencegahan dan Pengendalian HIV AIDS dan PIMS di Indonesia Tahun 2020-2024. Kementerian Kesehatan Republik Indones. 2020;1–188.
4. Anil A, Gedam S, Parashar N, Sethi G, Sethi S, L A, et al. A retrospective cohort study on the potential link between dolutegravir-based anti-retroviral therapy and weight gain compared to efavirenz-based anti-retroviral therapy in a tertiary care center in Jabalpur, Madhya Pradesh. Natl J Physiol Pharm Pharmacol. 2024;14(7):1454–8. https://doi.org/10.5455/njppp.2024.14.05215202429052024.
5. Tegegne B, Alehegn A, Kassahun M. Drug Use Evaluation of Tenofovir/Lamivudine/Dolutegravir (TLD) Fixed-Dose Combination for Initiation and Transition Among HIV-Infected Individuals Attending Lumame Primary Hospital, North West Ethiopia. Integr Pharm Res Pract. 2024;Volume 13(April):31–42. https://doi.org/10.2147/iprp.s455351.
6. Sabiti FB, Arief TA, Sofa NA, Saputra RA, Aryani IC, Nastiti NS, et al. Adherence of HIV/AIDS patients to clinical outcome in Semarang City. Pharm Educ. 2024;24(2):17–22. https://doi.org/10.46542/pe.2024.242.1722.
7. Indriastuti NA, Ayuningtyas R. Discriminatory behavior among people living with human immunodeficiency virus/acquired immune deficiency syndrome against adherence to antiretroviral treatment. Open Access Maced J Med Sci. 2021;9(April 2019):189–93. https://doi.org/10.3889/oamjms.2021.5803.
8. Turan B, Smith W, Cohen MH, Wilson TE, Adimora AA, Merenstein D, et al. Mechanisms for the negative effects of internalized HIV-related stigma on antiretroviral therapy adherence in women: The mediating roles of social isolation and depression. J Acquir Immune Defic Syndr. 2016;72(2):198–205. https://doi.org/10.1097/QAI.0000000000000948.
9. Ebrahimzadeh Z, Goodarzi MA, Joulaei H. Predicting the antiretroviral medication adherence and CD4 measure in patients with HIV/AIDS based on the post traumatic stress disorder and depression. Iran J Public Health. 2019;48(1):139–46. https://doi.org/10.18502/ijph.v48i1.802.
10. Effendy E, Amin MM, de Vega L, Utami N. The association between CD-4 level, stress and depression symptoms among people living with HIV/AIDS. Open Access Maced J Med Sci. 2019;7(20):3459–63. https://doi.org/10.3889/oamjms.2019.446.
11. Zuo L, Prather ER, Stetskiv M, Garrison DE, Meade JR, Peace TI, et al. Inflammaging and oxidative stress in human diseases: From molecular mechanisms to novel treatments. Int J Mol Sci. 2019;20(18). https://doi.org/10.3390/ijms20184472.
12. Valiaveettil C, Loutfy M, Kennedy VL, Caddy S, Yudin M, Conway T, et al. High prevalence of abnormal menstruation among women living with HIV in Canada. PLoS One. 2019;14(12):1–16. https://doi.org/10.1371/journal.pone.0226992.
13. Van Ommen CE, Hsieh AYY, Albert AY, Kimmel ER, Cote HCF, Maan EJ, et al. Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women. Aids. 2023;37(5):769–78. https://doi.org/10.1097/QAD.0000000000003481.
14. Chigbu UE, Atiku SO, Du Plessis CC. The Science of Literature Reviews: Searching, Identifying, Selecting, and Synthesising. Publications. 2023;11(2). https://doi.org/10.3390/publications11010002.
15. Al Husaeni DF, Nandiyanto ABD. Bibliometric Using Vosviewer with Publish or Perish (using Google Scholar data): From Step-by-step Processing for Users to the Practical Examples in the Analysis of Digital Learning Articles in Pre and Post Covid-19 Pandemic. ASEAN J Sci Eng. 2022;2(1):19–46. https://doi.org/10.17509/ajse.v2i1.37368.
16. Paul J, Barari M. Meta‐analysis and traditional systematic literature reviews What why when where and how? Psychol Mark. 2022;39:1099–115. http://dx.doi.org/10.1002/mar.21657
17. Higgins JPT, Green S, Ben Van Den A. Cochrane Handbook for Systematic Reviews of Interventions. Vol. 15, International Coaching Psychology Review. 2019. 693 p. https://doi.org/10.53841/bpsicpr.2020.15.2.123.
18. Ahmed A, Pereira L, Kimberly J. Mixed Methods Research: Combining Qualitative and Quantitative Methods. Mix Methods Res Comb Qual Quant Methods. 2023;(September). https://doi.org/10.4135/9781529666687.
19. Ohihoin AG, Ohihoin EN. First Line Anti-Retroviral ( ARV ) Drugs Disrupt Follicular Development in Female Wistar Rats. PMC. 2022;1–16. https://doi.org/10.21203/rs.3.rs-1538075/v1
20. Adebimpe O, Adebukola A, Oliwaseun A, Adediran A. MENSTRUAL CHANGES AMONG HIV POSITIVE WOMEN ON ANTI-RETROVIRAL TREATMENT IN SOUTHWESTERN NIGERIA. South Am J Med. 2015;2(2). https://doi.org/10.21522/TIJMD.2013.
21. Nhlongolwane N, Shonisani T. Predictors and Barriers Associated with Non-Adherence to ART by People Living with HIV and AIDS in a Selected Local Municipality of Limpopo Province, South Africa. Open AIDS J. 2024;17(1):1–8. https://doi.org/10.2174/18746136-v17-230726-2023-2.
22. Odubela OO, Peer N, Odunukwe NN, Musa AZ, Salako BL, Kengne AP. Weight changes among antiretroviral therapy-naïve people living with human immunodeficiency virus in Lagos, Nigeria. Front Public Heal. 2025;(May). https://doi.org/10.3389/fpubh.2025.1545676.
23. Luthuli MQ, John-Langba J. The Moderating Role of HIV Stigma on the Relationship between Perceived Social Support and Antiretroviral Therapy Adherence Self-Efficacy among Adult PLHIV in South Africa. J Int Assoc Provid AIDS Care. 2024;23:1–10. https://doi.org/10.1177/23259582241228743.
24. Patel PN, Grimes RM. Symptom exacerbation and adherence to antiretroviral therapy during the menstrual cycle: A pilot study. Infect Dis Obstet Gynecol. 2006;14869:1–4. https://doi.org/10.1155/IDOG/2006/14869.
25. Mahale PR, Patel BS, Kasmani N. Treatment Outcomes of Dolutegravir- Versus Efavirenz-Based Highly Active Antiretroviral Therapy Regimens Among Treatment-Naive People Living With HIV. Cureus. 2023;15(6). https://doi.org/10.7759/cureus.40139.
26. Susanti D, Nuryastuti T, Ikawati Z. Description of TLD (Tenofovir + Lamivudine + Efavirenz) Combined Antiretroviral Therapy Outcome in HIV Patients at RSUP Dr. Mohammad Hoesin Palembang. Maj Farm. 2024;20(2):299–308. https://jurnal.ugm.ac.id/majalahfarmaseutik/article/view/85457/40223
27. Umeokonkwo CD, Onoka CA, Agu PA, Ossai EN, Balogun MS, Ogbonnaya LU. Retention in care and adherence to HIV and AIDS treatment in Anambra State Nigeria. BMC Infect Dis. 2019;19(1):1–11. https://doi.org/10.1186/s12879-019-4293-8.
28. Herman JP, Mcklveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol. 2016;6(2):603–21. https://doi.org/10.1002/cphy.c150015.Regulation.
29. Yu HU, Wang W, Wenqing MA, Wang W, Wu REN, Wang S, et al. Impact of psychological stress on ovarian function: Insights, mechanisms and intervention strategies (Review). Int J Mol Med. 2025;55(2):1–29. https://doi.org/10.3892/ijmm.2024.5475.
30. Attia GM, Alharbi OA, Aljohani RM. The Impact of Irregular Menstruation on Health: A Review of the Literature. Cureus. 2023;15(11). https://doi.org/10.7759/cureus.49146.
31. Zaid D, Greenman Y. Human immunodeficiency virus infection and the endocrine system. Endocrinol Metab. 2019;34(2):95–105. https://doi.org/10.3803/EnM.2019.34.2.95.
32. James KA, Stromin JI, Steenkamp N, Combrinck MI. Understanding the relationships between physiological and psychosocial stress, cortisol and cognition. Front Endocrinol (Lausanne). 2023;14(March):1–20. https://doi.org/10.3389/fendo.2023.1085950.
33. Afifah LN, Arfijanto MV, Sa’adi A. Relationship Between Cd4 Levels and Menstrual Disorders in Women Hiv Patients At Dr Soetomo Hospital, Surabaya. Community Pract. 2023;20(8):302–8. https://doi.org/10.5281/zenodo.8296742.
34. Kvarnström K, Westerholm A, Airaksinen M, Liira H. Factors contributing to medication adherence in patients with a chronic condition: A scoping review of qualitative research. Pharmaceutics. 2021;13(7):1–41. https://doi.org/10.3390/pharmaceutics13071100.
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Copyright (c) 2025 Atika Nadia, Budi Prasetyo, Muhammad Vitanata Arfijanto (Author)
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