Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

Abstract Background Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART. Results We examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03). Conclusion HIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART.

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Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008–2013, Cameroon)

BMC Pediatrics ◽

10.1186/s12887-021-02664-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Francis Ateba Ndongo ◽

Mathurin Cyrille Tejiokem ◽

Calixte Ida Penda ◽

Suzie Tetang Ndiang ◽

Jean-Audrey Ndongo ◽

...

Keyword(s):

Cohort Study ◽

Viral Load ◽

Antiretroviral Therapy ◽

Antiretroviral Treatment ◽

Viral Suppression ◽

Virologic Response ◽

Sub Saharan Africa ◽

Factors Associated ◽

Sub Saharan

Abstract Background In most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon. Methods In the ANRS-12140 Pediacam cohort study, 2008–2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions. Results The viral load after five years of early ART was suppressed in 66.8% (60.1–73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0–74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1–6.8); p = 0.033). Conclusions The probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

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