TRIMETHOPRIM-SULFAMETHOXAZOLE FOR PNEUMOCYSTIS JIROVECII PNEUMONIA PROPHYLAXIS AMONG HIV-POSITIVE PATIENTS IN THE ERA OF EARLY ANTIRETROVIRAL THERAPY INITIATION
DOI:
https://doi.org/10.55374/jseamed.v7.162Keywords:
HIV, Early antiretroviral therapy, Pneumocystis jirovecii pneumonia, Trimethoprim-Sulfamethoxazole, ProphylaxisAbstract
Background: Trimethoprim-Sulfamethoxazole (TMP-SMX) is currently recommended for the primary prevention of Pneumocystis jirovecii pneumonia (PCP) among HIV-positive patients whose CD4 count is less than 200 cells/mm3. However, adverse drug reactions (ADR) have been reported among some patients. In the era of early antiretroviral therapy (ART) initiation, the prevalence of PCP has gradually decreased. Therefore, to avoid unnecessary ADR, TMP-SMX might be less beneficial when the patient receives early ART initiation.
Objectives: The study aimed to evaluate the incidence of PCP, all-cause mortality, CD4 count at 6 months after ART, other opportunistic infections (OIs), and ADRs among HIV-positive patients receiving early ART initiation with and without TMP-SMX for PCP prophylaxis.
Methods: This retrospective cohort study was conducted in Ratchaburi Hospital between January 2014 and February 2022. HIV-positive patients with an initial CD4 count <200 cells/mm3 or <14% and receiving early ART initiation within 2 weeks after HIV diagnosis were investigated. Patients with and without TMP-SMX prophylaxis were analyzed in terms of baseline characteristics, the incidence of PCP, all-cause mortality, other OIs and ADRs from TMP-SMX. The ratio of TMP-SMX vs. no TMP-SMX groups was 2:1.
Results: In total, 230 HIV-positive patients presenting an initial CD4 count <200 cells/mm3 or <14% were included in this study. All patients received early ART initiation within 2 weeks after HIV diagnosis and showed good adherence. The incidence of PCP in the TMP-SMX prophylaxis group was 2 of 153 cases (1.31%) and in the no prophylaxis group was 3 of 77 cases (3.89%), OR 0.329; 95% CI, (0.053 – 1.998); p=0.226. CD4 count at 6 months after ART initiation significantly increased in the no prophylaxis group (277.4 vs. 179.5 cells/mm3; mean difference 97.92; 95% CI of difference, (65.15-130.69); p <0.001). All-cause mortality and other bacterial and OIs did not differ between the two groups. All adverse events from TMP-SMX were minor rashes, 13 of 153 cases (8.5%).
Conclusion: Among HIV-positive patients receiving early ART initiation, the incidence of PCP revealed no difference between with and without TMP-SMX prophylaxis. All-cause mortality and rate of OI were also comparable between the 2 groups.
Metrics
References
Rojanawiwat A, Tsuchiya N, Pathipvanich P, Pumpradit W, Schmidt WP, Honda S, et al. Impact of the national access to antiretroviral program on the incidence of opportunistic infection in Thailand. Inter Health 2011; 3: 101-7. PMid:24038182 DOI: https://doi.org/10.1016/j.inhe.2010.12.004
Pulvirenti J, Herrera P, Venkataraman P, Ahmed N. Pneumocystis carinii Pneumonia in HIV-infected patients in the HAART era. AIDS Patient Care STDS 2003; 17: 261-5. PMid:12880489 DOI: https://doi.org/10.1089/108729103322108139
Gangcuangco LMA, Sawada I, Tsuchiya N, Alejandria M, Leyritana K, Yokomaku Y, et al. Regional differences in the prevalence of major opportunistic infections among antiretroviral-naive human immunodeficiency virus patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines. Am J Trop Med Hyg 2017; 97: 49-56. PMid:28719295 PMCid:PMC5508895 DOI: https://doi.org/10.4269/ajtmh.16-0783
Morris A, Lundgren JD, Masur H, Walzer PD, Hanson DL, Frederick T, et al. Current epidemiology of Pneumocystis Pneumonia. Emerg Infect Dis 2004; 10: 1713-20. PMid:15504255 PMCid:PMC3323247 DOI: https://doi.org/10.3201/eid1010.030985
Centers for Disease Control and Prevention. Pneumocystis pneumonia. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV 2022. Available at https://clinicalinfohivgov/en/guidelines/adult-and-adolescent-opportunistic-infection.
Chantachaeng W, Chularojanamontri L, Kulthanan K, Jongjarearnprasert K, Dhana N. Cutaneous adverse reactions to sulfonamide antibiotics. Asian Pac J Allergy Immunol 2011; 29: 284-9.
Björkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull World Health Organ 1991; 69: 297-304.
Wang L, Varghese S, Bassir F, Lo Y-C, Ortega CA, Shah S, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis:A systematic review of PubMed/MEDLINE case reports from 1980 to 2020. Front Med (Lausanne) 2022; 9: 949520. PMid:36091694 PMCid:PMC9449801 DOI: https://doi.org/10.3389/fmed.2022.949520
Teshale EH, Hanson DL, Wolfe MI, Brooks JT, Kaplan JE, Bort Z, et al. Reasons for lack of appropriate receipt of primary Pneumocystis jiroveci pneumonia prophylaxis among HIV-infected persons receiving treatment in the United States: 1994-2003. Clin Infect Dis 2007; 44: 879-83. PMid:17304464 DOI: https://doi.org/10.1086/511862
Lim PL, Zhou J, Ditango RA, Law MG, Sirisanthana T, Kumarasamy N, et al. Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the treat Asia HIV observational database. J Int AIDS Soc 2012; 15: 1. PMid:22281054 PMCid:PMC3354658 DOI: https://doi.org/10.1186/1758-2652-15-1
Bonora S, Di Perri G, Vento S, Cazzadori A, Concia E. Failure of prophylaxis against PCP in patients with HIV infection. AIDS Patient Care STDS. 1998; 12: 843-8. PMid:11362040 DOI: https://doi.org/10.1089/apc.1998.12.843
Moorman AC, Von Bargen JC, Palella FJ, Holmberg SD. Pneumocystis carinii Pneumonia incidence and chemoprophylaxis failure in ambulatory HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 19: 182-8. PMid:9768629 DOI: https://doi.org/10.1097/00042560-199810010-00013
Ruxrungtham K, Chokephaibulkit K, Chetchotisakd P, Chariyalertsak S, Kiertburanakul S, Putcharoen O, et al. Thailand national guidelines on HIV/AIDS treatment and prevention 2021/2022. Nonthaburi: Division of AIDS and STIs, Department of Disease Control; 2022. Available at https://www.thaiaidssociety.org/wp-content/uploads/2023/03/HIV-AIDS-Guideline-2564_2565_ED2.pdf (thaiaidssociety.org)
Alanio A, Hauser PM, Lagrou K, Melchers WJG, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 2016; 71: 2386-96. PMid:27550991 DOI: https://doi.org/10.1093/jac/dkw156
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 2022; 329: 63-84. PMid:36454551 DOI: https://doi.org/10.1001/jama.2022.22246
Turner BJ. Adherence to antiretroviral therapy by human immunodeficiency virus-infected patients. J Infect Dis 2002; 185 (Suppl2): S143-51. PMid:12001036 DOI: https://doi.org/10.1086/340197
Giuseppe C, Fabrizio F, Silvia C, Paolo B, Lucia L, Francesca S, et al. Mild cutaneous reactions to drugs. Acta Biomed 2019; 90 (Suppl3): 36-43.
Costiniuk CT, Fergusson DA, Doucette S, Angel JB. Discontinuation of Pneumocystis jirovecii Pneumonia prophylaxis with CD4 count <200 cells/µL and virologic suppression: a systematic review. PLoS One 2011; 6: e28570. PMid:22194853 PMCid:PMC3241626 DOI: https://doi.org/10.1371/journal.pone.0028570
Mocroft A, Reiss P, Kirk O, Mussini C, Girardi E, Morlat P, et al. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/ µL. Clin Infect Dis 2010; 51: 611-9. PMid:20645862 DOI: https://doi.org/10.1086/655761
Downloads
Published
How to Cite
Issue
Section
License
The Journal of Southeast Asian Medical Research will hold the copyright to all published articles. The publisher's production department handles copyright forms once a manuscript is accepted and scheduled for publication.
