Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

Abstract

Background. The therapeutic goal of antiretroviral therapy (ART) is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line HAART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592) of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm 3 , 70% (n=645) of patients had a haemoglobin level >11 g/dl and 88% (n=803) were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP). Six months after ART initiation, 24% (n=220) of patients had a discordant immune response and 7% (n=67) a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm 3 (AOR 3.02; 95% confidence interval (CI) 2.08 -4.38; p<0.001) and moderate anaemia (8.0 -9.4 g/dl) at baseline (AOR 2.30; 95% CI 1.25 -4.59; p=0.007) were independently associated with the development of discordant immune response, after adjustment for education level, World Health Organization (WHO) clinical stage and ART regimen. Conclusions. Discordant immune response following ART initiation was common and associated with baseline anaemia and CD4 cell count in our cohort. Intensive monitoring of at-risk individuals may improve clinical outcomes.

Immunological outcomes of Tenofovir versus Zidovudine-based regimens among people living with HIV/AIDS: a two years retrospective cohort study

“…The bi-phasic CD4+ count response shown in our finding was also reported by other findings [ 18 , 19 ] as a rapid increase of memory CD4+ cells (a high CD4+ count slope) in the first several months after treatment initiation succeeded by a slow increase in naive CD4+ cells (smaller slope compared to the initial several months). The linear trend in CD4+ increment at early phase of of therapy became flat with minimal CD4+ gain latter after 18th month of treatment irrespective of the regimen used.…”

“…Immunologic response after 6 months of ART indicates a favourable clinical outcome in HIV-1 infected patients regardless of virologic response [ 20 ]. Several studies has reported that as many as 8–40% of patients on ART do not show a significant increase in CD4+ cell count despite viral suppression [ 18 , 21 , 22 ]. Our finding, in general, is almost consistent with these studies.…”

“…So, it is not surprising that most of these patients in this study were from TDF based regimens. As the recovery of the CD4+ T-cell count is hindered by several patient and viral factors, including: residual viral replication, impaired thymic function, advanced age, enhanced T-cell activation and apoptosis, genetic variations, baseline anaemia and poor adherence [ 18 , 21 , 23 , 24 ], our finding might not quest the efficacy of TDF based regimens in resource limited settings, even though it needs a further workup with adequately powered and methodological high quality study.…”

“…As this study has short comings including absence of viral marker measurement to conclude the rate of sub-optimal immunologic recovery among the patients, further study with quality design is needed as lack of knowledge about this subgroup may contribute to inadequate clinical management and current HIV treatment guidelines do not provide specific applicable guidance [ 18 ].…”

<p>Predictors of Clinical and Immunological Failure Among Patients on First-Line Antiretroviral Therapy (ART) in Southwest Ethiopia</p>

“…The result is supported by finding from a study conducted in Johannesburg, South Africa. 26 In most the case, anemic patients are more likely to have advanced immunosuppression and a higher rate of comorbidities which could impose a negative effect of response to ARV treatments. Evidence from other studies also shows anemia at ART initiation associated with increased mortality, disease progression (poor virologic response) and reduced quality of life.…”