Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study

Abstract

BackgroundA paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell-count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART.MethodsA case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. Cases: patients with PIR, defined as CD4 < 350 cells/mm3 (hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. Controls: similar to cases, but with CD4 counts ≥ 350 cells/mm3. Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis.ResultsAmong 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99).ConclusionsPIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses.

Initial suboptimal CD4 reconstitution with antiretroviral therapy despite full viral suppression in a cohort of HIV-infected patients in Senegal

“…Le nombre de patients dont les CD4 étaient disponibles à chaque semestre sont listés en dessous. in patients with a CD4 count < 350 cells/mm 3 at 12 months of treatment, but did not find it significant [14]. Triple therapy, including tenofovir (TDF) in combination with lamivudine (3TC) or emtricitabine (FTC) and a non-nucleoside reverse transcriptase inhibitor (NNRTI), was associated with a lower rate of slow reconstitution at six months of treatment, compared to a regimen containing AZT.…”

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

“…+ T cell nadir and a poor immunological response to HAART [27,28,39,41,42]. In particular, Mendes-Lagares et al have pointed out the role of Tregs in the control of naive CD4…”

“…The CD4 + T cell count nadir is a well-known and wellvalidated predictor of immune response to HAART [41,43]. It is believed that an early diagnosis and suppression of HIV replication could increase the probability of achieving immunological response to HAART by limiting the magnitude of CD4 + T count nadir [44].…”

Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa

“…19 Although CD4+ counts increased, indicating immunologic recovery, only 66% of patients in the NRTI group had a CD4+ count of more than 250 cells per cubic millimeter by 96 weeks, which probably reflects the low baseline CD4+ counts in patients at the time of the switch to secondline therapy. 20 However, even with persistently low CD4+ counts, patients receiving antiretroviral therapy would be expected to have reduced rates of HIV-related complications. 21 Raltegravir was not superior to NRTIs when used in combination with a protease inhibitor in second-line therapy -an unexpected finding, given the predicted benefit associated with adding a second new drug class without overlap with first-line treatment regimens.…”