Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia

Abstract

Background There is very little data on long-term immune recovery responses in patients on suppressive antiretroviral therapy (ART) in the setting of sub-Saharan Africa (SSA). Thus, we sought to determine CD4+ T-cell, CD8+ T-cell and CD4/CD8 ratio responses in a cohort of HIV infected individuals on sustained suppressive ART followed up for more than a decade. Methods The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 14 years. Trends in median CD4+ T-cells, CD8+ T-cells and CD4/CD8 ratio were reviewed retrospectively. Poisson regression models were used to identify factors associated with achieving normalized T-cell biomarkers. Kaplan-Meier curves were used to estimate the probability of attaining normalized counts while on suppressive ART. Results A total of 227 patients with a median duration of follow-up on ART of 12 (IQR: 10.5–13.0) years were included. CD4 cell count increased from baseline median of 138 cells (IQR: 70–202) to 555 cells (IQR: 417–830). CD4 cell increased continuously up until 5 years, after which it plateaued up until 14 years of follow up. Only 69.6% normalized their CD4 cell count within a median of 6.5 (IQR: 3.0–10.5) years. In addition, only 15.9% of the cohort were able to achieve the median reference CD4+ T-cell threshold count in Ethiopians (≈760 cells/μL). CD8+ T-cell counts increased initially until year 1, after which continuous decrease was ascertained. CD4/CD8 ratio trend revealed continuous increase throughout the course of ART, and increased from a median baseline of 0.14 (IQR: 0.09–0.22) to a median of 0.70 (IQR: 0.42–0.95). However, only 12.3% normalized their ratio (≥ 1.0) after a median of 11.5 years. In addition, only 8.8% of the cohort were able to achieve the median reference ratio of healthy Ethiopians. Conclusion Determination of both CD4+ and CD8+ T-cells, along with CD4/CD8 ratio is highly relevant in long-term follow-up of patients to assess immune recovery. Monitoring ratio levels may serve as a better biomarker risk for disease progression among patients on long-term ART. In addition, the findings emphasize the relevance of initiation of ART at the early stage of HIV-1 infection.

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

“…This shows that there is a normal recovery of CD4 + T cell counts in patients who are only infected with Leishmania parasites. It has been shown that despite ART, poor recovery of CD4 + T cell counts is common, especially in individuals who start ART with low CD4 + T cell counts 45 , 46 , 47 ; and results of a multi-country prospective cohort study in sub-Saharan Africa showed a suboptimal recovery of CD4 + T cells despite sustained viral suppression on continuous first-line ART. 48 In addition to bone marrow failure, reduced thymic output may play a role in the lower number of CD4 + T cells, and indeed, a recent study showed a clear correlation between decreased numbers of recent thymic emigrants and poor CD4 + T cell recovery in HIV patients.…”

“…d HIV treatment: ART was provided according to the National guideline for comprehensive HIV prevention, care and treatment. 46 VL/HIV patients were on ART at the time of VL diagnosis, the remaining three started ART at the end of the anti-leishmanial treatment, all patients were on ART following the Ethiopian national guidelines for comprehensive HIV prevention, care, and treatment, and the following combination therapies were used Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) + Efavirenz (EFV), azidothymidine (AZT) + 3TC + EFV or TDF + 3TC + atazanavir (ATV).…”

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

“…This shows that there is a normal recovery of CD4 + T cell counts in patients who are only infected with Leishmania parasites. It has been shown that despite ART, poor recovery of CD4 + T cell counts is common, especially in individuals who start ART with low CD4 + T cell counts (44)(45)(46); and results of a multi-country prospective cohort study in sub-Saharan Africa, showed a suboptimal recovery of CD4 + T cells despite sustained viral suppression on continuous first-line ART (47). In addition to bone marrow failure, reduced thymic output might also play a role in the low number of CD4 + T cells, and indeed, a recent study showed a clear correlation between decreased numbers of recent thymic emigrants and poor CD4+ T cell recovery in HIV patients (48).…”

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

“…The evidence suggests that the immune dysfunction plays a crucial role in HIV pathogenesis, leading to non‐AIDS morbidity and mortality in PLWH [ 24 , 25 , 26 , 27 , 28 , 29 ]. First children infected at the beginning of the HIV pandemic are now reaching adulthood, but studies regarding the evolution of the immune system of YWVH are rather scarce.…”