Therapeutic Monitoring of Antiretroviral Drugs in Immunologically Stable HIV Patients on ART Treatment
In HIV, highly active anti-retroviral therapy helps patients to regain the immune CD4+ cell count. Among all antiretroviral therapy (ART) regimens tenofovir based regimen (TLE; Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV)) has become the most preferred first line regimen. Present study aimed to identify the therapeutic levels of drugs in tenofovir based regimen in immunologically stable HIV patients. A total of 35 dried blood samples were obtained from HIV patients on TLE treatment visiting ART centre, Mahatma Gandhi Memorial (MGM) Hospital, Warangal, Telangana, during September 2017 to March 2018. Patients with good adherence, without history of smoking & alcoholism and with CD4+ cell count > 350 cells/mm3 were included. Estimation of drugs was done using pre validated liquid chromatographic method. In total of 35 patients, females were accounted for 62.86%. Patients of this study showed high percentage of illiterates (48.57%) and daily labors (34.29%). As EFV is a narrow therapeutic index drug it showed significant difference in its plasma therapeutic levels (0.005**) whereas TDF & 3TC were not. Total of 8.57% and 91.43% patients were showed EFV plasma levels below and above therapeutic levels respectively. Though the study patients observed with good immunological status, high percentage of patients identified with toxic levels of EFV concentrations. But none of the patients showed any symptoms of toxicity, they are at risk to develop clinical toxicity in future. Present study results suggesting dose adjustments and monitoring of drug levels in these patients to avoid early treatment failures and toxicity.
Keywords: HIV, CD4+ cell count, Tenofovir regimen, Therapeutic level, Monitoring.
2. http://naco.gov.in/hiv-facts-figures. NACO 2018. (Accessed on 20th January, 2019).
3. http://www.naco.gov.in/sites/default/files/listart.pdf. NACO 2018. (Accessed on 10th February, 2019).
4. Paranjape RS, Immunopathogenesis of HIV infection, Indian Journal of Medical Research, 2005; 121:240-255.
5. Maini MK, Gilson RJC, Chavda N, Gill S, Fakoya A, Ross EJ, et al., Reference ranges and sources of variability of CD4 counts in HIV seronegative women and men, Genitourinary Medicine, 1996; 72:27-31.
6. Panchagiri S, Begum A, Valupadas C, & Ciddi V, Quantitative bio-analysis of Tenfovir disoproxil fumarate, Lamivudine and Efavirenz simultaneously in human plasma using reverse-phase liquid chromatography, Acta Scientific Pharmaceutical Sciences, 2018; 2(10):17-27.
7. Trotta MP, Cozzi‐Lepri A, Ammassari A, Vecchiet J, Cassola G, Caramello P, et al., Rate of CD4+Cell Count Increase over Periods of Viral Load Suppression: Relationship with the Number of Previous Virological Failures, Clinical Infectious Diseases, 2010; 51(4):456-464.
8. WHO 2018. https://www.who.int/hiv/pub/guidelines/arv2013/art/artadults/en/. (Accessed on 11th December, 2018).
9. Marzolini C, Telenti A, Decosterd LA., Greub G, Biollaz J, & Buclin T, Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients, AIDS, 2001; 15(1):71–75.
10. Boerma JT, Ghys PD, & Walker N, Estimates of HIV-1 prevalence from national population-based surveys as a new gold standard, The Lancet, 2003; 362(9399):1929–1931.
11. Shen Z, Zhu Q, Tang Z, Pan SW, Zhang H, Jiang H, et al., Effects of CD4 Cell Counts and Viral Load Testing on Mortality Rates in Patients With HIV Infection Receiving Antiretroviral Treatment: An Observational Cohort Study in Rural Southwest China, Clinical Infectious Diseases, 2006; 63(1):108–114.
12. Lakhashe S, Thakar M, Godbole S, Tripathy S, & Paranjape R, HIV infection in India: Epidemiology, molecular epidemiology and pathogenesis, Journal of Biosciences, 2008; 33(4):515–525.
13. Kumarasamy N, Solomon S, Chaguturu SK, Cecelia AJ, Vallabhaneni S, Flanigan TP, & Mayer KH, The Changing Natural History of HIV Disease: Before and After the Introduction of Generic Antiretroviral Therapy in Southern India, Clinical Infectious Diseases, 2005; 41(10):1525–1528.
14. Godbole S, Sane S, Kamble P, Raj Y, Dulhani N, Venkatesh S, et al., Predictors of Bisexual Behaviour among MSM Attending Intervention Sites May Help in Prevention Interventions for This Bridge to the Heterosexual Epidemic in India: Data from HIV Sentinel Surveillance, PLoS ONE, 2014; 9(9):e107439.
15. Obiako OR, Muktar HM, Garko SB, Ajayi-Tobi E, Olayinka AT, et al., Adverse Reactions Associated with Antiretroviral Regimens in Adult Patients of a University Teaching Hospital HIV Program in Zaria, Northern Nigeria: An Observational Cohort Study, Journal of Antiviral and Antiretrovirals, 2012; 4:006–013.
16. Sood A, Prajapati H, Bhagra S, & Bansal R, Characterization and comparative analysis of ADRs of various ART regimens: experience of our medical college from Western Himalayan region. Interantional Jouranl of Research in Medical Sciences, 2017; 5(2):659–665.
17. Burger D, van der Heiden I, la Porte C, van der Ende M, Groeneveld P, Richter C, et al., Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism, British Journal of Clinical Pharmacology, 2006; 61(2):148–154.
18. Luetkemeyer AF, Rosenkranz SL, Lu D, Marzan F, Ive P, Hogg E, et al., Relationship Between Weight, Efavirenz Exposure, and Virologic Suppression in HIV-Infected Patients on Rifampin-Based Tuberculosis Treatment in the AIDS Clinical Trials Group A5221 STRIDE Study, Clinical Infectious Diseases, 2013; 57(4):586–593.
19. Chittick GE, Zong J, Blum MR, Sorbel JJ, Begley JA, Adda N, & Kearney BP, Pharmacokinetics of Tenofovir Disoproxil Fumarate and Ritonavir-Boosted Saquinavir Mesylate Administered Alone or in Combination at Steady State, Antimicrobial Agents and Chemotherapy, 2006; 50(4):1304–1310.
20. Kearney BP, Flaherty JF, & Shah J, Tenofovir Disoproxil Fumarate, Clinical Pharmacokinetics, 2004; 43(9):595–612.
21. Kano EK, Serra CHR, Koono EEM, Andrade SS, & Porta V, Determination of lamivudine in human plasma by HPLC and its use in bioequivalence studies, International Journal of Pharmaceutics, 2005; 297(1-2):73–79.
22. Byakika-Kibwika P, Lamorde M, Kalemeera F, D’Avolio A, Mauro S, Di Perri G, et al., Steady-state pharmacokinetic comparison of generic and branded formulations of stavudine, lamivudine and nevirapine in HIV-infected Ugandan adults, Journal of Antimicrobial Chemotherapy, 2008; 62(5):1113–1117.
23. Manosuthi W, Sungkanuparph S, Tantanathip P, Mankatitham W, Lueangniyomkul A, Thongyen S, et al., Body Weight Cutoff for Daily Dosage of Efavirenz and 60-Week Efficacy of Efavirenz-Based Regimen in Human Immunodeficiency Virus and Tuberculosis Coinfected Patients Receiving Rifampin, Antimicrobial Agents and Chemotherapy, 2009; 53(10):4545–4548.
24. Poeta J, Linden R, Antunes MV, Real L, Menezes AM, Ribeiro JP, & Sprinz E, Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals, Journal of Antimicrobial Chemotherapy, 2011; 66(11):2601–2604.
25. Bisson GP, Gross R, Strom JB, Rollins C, Bellamy S, Weinstein R, et al., Diagnostic accuracy of CD4 cell count increase for virologic response after initiating highly active antiretroviral therapy. AIDS, 2006; 20(12):1613–1619.
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