Immunologic Response of HIV-Infected Children to Different Regimens of Antiretroviral Therapy: A Retrospective Observational Study

Abstract

Background. Both abacavir- (ABC-) based and zidovudine- (AZT-) based regimens are widely utilized for managing HIV infection in children. Unfortunately, there is a lack of data regarding their immunological response and associated risk factors in Ethiopia. Methods. A retrospective hospital-based cohort study was conducted on HIV-infected children in Jimma Medical Center (JMC). A total of 179 records were reviewed by including data from November 2015 to April 2017. Data were collected on sociodemographic, clinical characteristics of patients and drug-related variables. Data analysis was done using STATA 13.1. Mixed-effect linear regression was performed to assess the difference in CD4+ changes between groups adjusting for baseline characteristics. The change in predicted CD4 count attributed to each regimen was also assessed by marginal analysis. P<0.05 for slope of the random-effect linear regression was used as an indicator for the presence of association. Result. Of 179 patients, 98 (54.7%) were females. The mean (±SD) duration of follow-up was 939.8 ± 478.3 and 984.92 ± 453.1 days for ABC and AZT groups, respectively. AZT group had a significant CD4+ count gain per visit compared with their ABC counterparts ((β = 20.51, 95% CI [6.37–34.65]), P=0.004) over time. The regimen AZT + 3TC + LPV/r tended to have an excellent predicted CD4+ lymphocyte count change relative to all other regimens, while ABC + 3TC + LPV/r had the least immunologic recovery (margins 338.0 cells/mm3 versus 249.13 cells/mm3 (P<0.001)). Baseline CD4+ lymphocyte count, ART group, WHO clinical stages, and viral load were independent predictors for CD4+ change overtime. Conclusion. AZT-based regimens seem to have better immunological response compared to ABC-based regimens. Immunologic response was described worse in patients with a viral load of >1000copies/ml, low baseline CD4+ count, advanced WHO clinical stages, and ABC-containing regimens. Further study is needed to clarify these aspects.

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

“…As a consequence, mortality in HIV patients has decreased significantly [2][3][4]. However, drug-induced side effects associated with longterm antiretroviral therapy are becoming a growing concern [2,3,5]. HIV therapy involves highly active antiretroviral therapy (HAART), meaning that patients are treated with drug combinations.…”

Safety and efficacy of abacavir for treating infants, children, and adolescents living with HIV: a systematic review and meta-analysis

“…12 (50%) were prospective cohort studies, 15,[22][23][24][25][26][27][28][29][30][31][32] including one cohort nested in an RCT. 22 Seven (29%) were retrospective cohort studies 14,[33][34][35][36][37][38] and two (8%) were crosssectional surveys. 19,39 These studies were conducted in various settings; nine (38%) in southern Africa (Zambia, South Africa, and Zimbabwe), six (25%) in eastern Africa (Ethiopia, Uganda, and Malawi), two (8%) in western Africa (Ghana and Nigeria), three (13%) in south Asia (India), three (13%) in Europe, and three (13%) in North America.…”

“…One study showed higher CD4 count gain at 6 months for zidovudinebased regimens compared with abacavirbased regimens. 37 Most outcomes were reported heterogeneously between studies, and except for two randomised trials, studies were considered of moderate to high risk of bias. Therefore, data inter pretation needs to be made cautiously.…”

“…Cassim et al (2017) 33 Crichton et al (2020) 29 de Waal et al (2020) 24 Dirajlal-Fargo et al (2017) 22 Fortuny et al (2014) 21 Mulenga et al (2016) 13 Technau et al (2013) 14 Four studies reported CD4 data related to abacavir treatment, 20,30,33,37 and three of these studies compared abacavir with other ARTs. In the studies by Strehlau and colleagues 20 and Cassim and colleagues, 33 the CD4 per centages (defined as the proportion of all lymphocytes that are CD4 cells) were similar between the abacavir and stavudine groups over time (at 26, 32, 52, and 56 weeks; appendix p 14).…”

Population-Specific Predictors of Immunologic Reconstitution Following Initiation of Combined Antiretroviral Therapy in Children: A Retrospective Observational Study from a 15-year Cohort of HIV-Positive Children and Adolescents in Eritrea

“…Moreover, many children are inclined to exhibit poor immunologic response due to the variations arising from the response to therapy that may increase their risk of morbidity and mortality despite the widespread use of cART 23,24 . In prior studies, a multitude of sociodemographic and clinical parameters have been found to in uence IR in HIVinfected pediatric patients following cART initiation: Baseline CD4 + lymphocyte count, cART group, WHO clinical stages, initial nutritional status, tuberculosis and the presence of anemia have all been found to in uence CD4 + count reconstitution 23,24 . Nonetheless, with the existing data and the lines of evidence, the depth of knowledge in the Sub-Saharan context remains sparse.…”