Predictors of virologic response in persons who start antiretroviral therapy during recent HIV infection

Abstract

Objective Despite evidence supporting antiretroviral therapy (ART) in recent HIV infection, little is known about factors that are associated with successful ART. We assessed demographic, virologic, and immunologic parameters to identify predictors of virologic response. Design A 24-week observational study of ART on persons enrolled within 6 months of their estimated date of infection (EDI) evaluated baseline demographics and the collection of blood and gut specimens. Methods Flow cytometry analyses of blood and gut lymphocytes allowed characterization of CD4+ and CD8+ T cells at study entry and end. Additional assessments included soluble CD14 (sCD14), lipopolysaccharide, CD4+ T-cell counts, and HIV RNA levels. Results Twenty nine participants initiated ART, and 17 achieved undetectable HIV RNA by study end. A longer time from EDI to ART, older age, higher sCD14, lower proportions of central memory CD4+ T cells, and higher proportions of activated CD8+ T cells were associated with detectable viremia. Multivariable logistic regression found only older age and elevated sCD14 were independently associated with persistent viremia. Additionally, we observed that ART in recent infection did not result in discernible recovery of CD4+ T cells in the gut. Conclusion In persons who started ART within 3–33 weeks from EDI, age and microbial translocation were associated with detectable HIV RNA. As observed in other cohorts, ART in recent infection did not improve proportions of total CD4+ T cells in gut-associated lymphoid tissue (GALT). This lends support to further evaluate the use of more potent ART or regimens that protect the GALT in recent HIV infection.

Impact of early cART in the gut during acute HIV infection

“…This dichotomy suggests that the previously observed increases occurred within lymphoid tissue structures (e.g., lymphoid aggregates) and not within the effector sites of the gut. This is in concordance with several previous studies demonstrating that CD4 + T cells in the GI tract remained significantly lower than in HIV − controls, despite effective prolonged cART (14, 39–43). It is encouraging to note that several individuals treated during FI/II approached HIV − baseline CD4 + T cell levels in the LP and demonstrated significant increases in CD4 + T cells from the 24 to 96 week time point.…”

Correlation of (1→3)-β-D-glucan with other inflammation markers in chronically HIV infected persons on suppressive antiretroviral therapy

“…The enteropathy associated with HIV infection is characterized by microbial over-growth in the intestinal lumen and disrupted intestinal permeability resulting in increased levels of lipopolysaccharides (LPS) and 16S rRNA in blood plasma. Such microbial translocation most likely leads to local and systemic immune activation, characterized by increased levels of pro-inflammatory cytokines such as tumour-necrosis-factor α (TNF-α), neopterin, cluster of differentiation 14 (CD14), interleukin-8 (IL-8), and interleukin-6 (IL-6) [6], [7], [8], [9]. In particular, plasma neopterin is an established marker of monocyte activation and was repeatedly associated with HIV disease progression, greater peripheral monocyte HIV DNA reservoirs and negative neurocognitive and cardiovascular outcomes [10], [11], [12].…”

Immune recovery uveitis in HIV patients with cytomegalovirus retinitis in the era of HAART therapy—a 5-year study from Singapore

“…Hartigan-O’Connor et al previously reported that IRU is most likely to develop in patients with the greatest degree of immune dysfunction prior to HAART [22]. Additionally, older age groups have been correlated with quicker seroconversion to AIDS in the pre-HAART era, as well as higher rates of immunologic failure and persistent HIV viraemia in the HAART era [23]. Thus, it is plausible that younger HIV patients have a more intact immune system that may not have such heightened sensitivity to CD4 T cell responses, consequently delaying their development of IRU until the occurrence of further immune dysfunction.…”