Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy within the International Epidemiologic Databases to Evaluate AIDS in East Africa

Abstract

Objective To describe patterns of suboptimal immune recovery (SO-IR) and associated HIV-related-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa. Design Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania). Methods SO-IR was described by proportions of ART-treated adults with CD4+ cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan–Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4+ cell counts less than 200, 200–350, 351–499, and >500 cells/μl, respectively. Results Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4+ cell count was 126 [interquartile range (IQR), 52–202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4+ cell counts less than 200 and 200–350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 <200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47–16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03–12.94)] and herpes zoster [incident rate 6.30 (5.99–6.64)] events/100 PYAR. With attainment of a CD4+ cell count level 200–350 cells/μl, there was a substantial reduction in events/100 PYAR – by 91% to 1.45 (1.29–1.63) for TB, by 94% to 0.75 (0.64–0.89) for oral candidiasis, by 84% to 0.99 (0.86–1.14) for Herpes Zoster, and by 78% to 1.22 (1.07–1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds. Conclusion Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/ml after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events.

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

“…Noteworthy, majority of the ART-treated adults with CD4 counts ≥ 500 cells/ul in this study were female, which reflects the sub-Saharan HIV epidemic where women are disproportionately more affected than men. In our previous analysis of immune recovery among ART-treated adults in Uganda, Kenya, and Tanzania over 65% of HIV-treated individuals were female although there was no statistical difference in gender among ART-treated adults with CD4 counts above and below 500 cells/μl after five years of treatment [ 34 , 35 ], yet CD4 counts in the general healthy the Ugandan population tend to be higher in women than men [ 36 ]. However differences in NK cell phenotypes among healthy HIV-negative men and women are yet to be studied.…”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…The duration of ART can significantly affect the magnitude of immune reconstitution in HIV‐1‐infected patients, thus hindering the comparison of different findings. According to the heterogeneity among study populations and discrepancy in definitions, the prevalence of INRs varies from 10% to 40% . In contrast, an adequate immune response to ART is defined as CD4 + T‐cell counts >500 cells/µl, mainly because HIV‐1‐infected patients with this level of immune restoration have a morbidity and mortality rate approaching or comparable to those of HIV negative individuals .…”

“…According to the heterogeneity among study populations and discrepancy in definitions, the prevalence of INRs varies from 10% to 40%. 7,14,15 In contrast, an adequate immune response to ART is defined as CD4 + T-cell counts >500 cells/µl, mainly because HIV-1-infected patients with this level of immune restoration have a morbidity and mortality rate approaching or comparable to those of HIV negative individuals. 13,[16][17][18] In addition, the Department of Health and Human Services (DHHS) considered that patients with CD4 + T-cell counts that had not increased to 350-500 cells/µl after 4-7 years of effective ART were defined as INRs.…”

Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome

“…Most patients can achieve significant viral load reduction and peripheral blood CD4 + T cell reconstruction. However, although some patients achieve virological suppression after ART, the reconstruction of CD4 + T cells is still insufficient (Lu et al, 2015); these individuals are known as INRs, and the prevalence ranges from 10 to 40% (Massanella et al, 2013;Nakanjako et al, 2016). Compared with those who had good immune reconstitution, the INRs showed chronic immune activation and high inflammatory state, which was related to the high incidence rate of cardiovascular diseases, metabolic diseases, and cancer (Paiardini and Muller-Trutwin, 2013;Nix and Tien, 2014).…”