Pre-HAART CD4+ T-lymphocytes as biomarkers of post-HAART immune recovery in HIV-infected children with or without TB co-infection

Abstract

Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection. Results We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

Subdividing ART patients and analyzing the medical burden by modeling of CD4 cell count

“…Since the CD4 cell count represents an important diagnostic indicator for post-ART immune recovery,[ 18 ] we conducted CFA on the three indicators of baseline/mean/last CD4 cell counts. The results showed them to be important variables, as shown in Table 2 .…”

“…[ 6 , 21 22 23 ] Poor immune reconstitution was defined as having a last CD4 cell count of <500 cells/μL. [ 18 ] We used the baseline/mean/last CD4 cell counts as variables in the modeling, and the ART-treated patients were subdivided into 15 types [ Table 3 ].…”

“…The CD4 cell count is an important diagnostic indicator for post-ART immune recovery. [ 18 ] The baseline, mean, and last CD4 cell counts indicate the immunity level of the body at the initial treatment, during the treatment, and after the treatment, respectively. According to literature,[ 26 , 27 ] the three variables of the baseline/last/mean CD4 cell counts were subjected to common factor analysis (CFA) to obtain critical variables [ Table 2 ].…”

“…Since the CD4 cell count is considered as an important diagnostic indicator for immune recovery after ART,[ 18 ] different treatment measures can be considered for different types of ART patients, thereby reducing the medical burden. [ 1 , 6 ] The key to reduce the costs could be the accurate subdivision of ART-treated patients according to their needs.…”

A study of the top-cited studies on drug therapy for HIV

“…In order to control this disease, it was very important to diagnose the disease early, start the treatment early, and keep the treatment persistence of the virus load suppressed ( Shahriar et al, 2021 ; Annor et al, 2022 ). Free highly active antiretroviral therapy (HAART) was very important ( Bani et al, 2020 ; Gopalakrishnan et al, 2020 ; Mai et al, 2020 ; Getaneh et al, 2021 ). The introduction of HAART effectively reduced the burden of HIV ( Bani et al, 2020 ; Getaneh et al, 2021 ).…”