Loss of CD127 & increased immunosenescence of T cell subsets in HIV infected individuals.

Background & objectives: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naïve T cell subsets in HIV-infected and uninfected individuals. Methods: We characterized T cell subsets based on expression of these markers, and compared their expression pattern in HIV infected subjects and uninfected controls. We further assessed therapy generated changes in these subsets and expression of CD127 and CD57 on them. Results: There was a generalized decrease in naïve CD4 and CD8 T cells in HIV infected subjects. These changes in T cell subset distribution were related to antigen load. CD127 expression was significantly reduced in T cells from HIV infected subject. In association to this, HIV infected subjects had higher percentage of T cell subsets expressing CD57. Increased CD57 and reduced CD127 expression correlated with plasma viraemia and CD8 T cell activation state. Incomplete restoration of T cell subset proportions was observed, despite suppression of viral replication and increase in CD4 T cell counts. Further, the improvement was more pronounced in CD127 expression. Interpretation & conclusions: HIV infected subjects have reduced T cell regenerative capacity along with increased senescence, highlighting decreased proliferation and effector activities.

Defects in blood dendritic cell subsets in HIV-1 subtype C infected Indians.

Background & objective: DCs trigger both innate and adaptive immune responses to control HIV infection and represent a viral reservoir acting as target and HIV carriers for infection of permissive CD4+ T-cells. DCs thus form a very attractive study subject to further our existing knowledge of HIV induced immunopathogenesis due to its diverse and crucial role in HIV infection establishment, viral dissemination, immune evasion, viral persistence, etc. We aimed to characterize the effect of HIV infection on myeloid and plasmacytoid dendritic cell subsets in a group of HIV-1 subtype C infected treated or untreated Indian individuals. Methods: Blood DC subset numbers and immunophenotype were studied for 79 HIV infected subjects at various stages of disease and compared with 13 HIV-uninfected controls. Comparisons were also made between groups of subjects based on their CD4+ T cell counts and also experience of antiretrovirals. Results: Significant decreases were observed in blood DC counts and the two DC subsets in HIV infected individuals. Subjects with lowest CD4+ T cell counts also had a drastically reduced DC subset pool which correlated positively with plasma viraemia and negatively with CD4+ T cell counts. DC subsets from HIV infected subjects showed higher expression of co-stimulatory molecules CD40 and CD86, and HIV-1 co-receptors CXCR4 and CCR5 which correlated positively with HIV-1 plasma viraemia. The alterations in blood DCs were partly resolved in ART receiving study subjects. Interpretation & conclusions: Correlation between DC subset activation state and viraemia supports the role of DC activation on viral replication and CD4+ T cell depletion.

Antiretroviral treatment in resource-poor settings: a view from India.

CONTEXT: The introduction of highly effective generic antiretroviral drugs at reduced cost has transformed the face of HIV/AIDS epidemic in developing countries like India. However, there is an urgent emphasis on developing and implementing guidelines for antiretroviral treatment monitoring by laboratory methods utilizing the available technologies in resource-limited settings. AIM: We studied the efficacy of antiretroviral treatment, adherence to therapy and motivation of patients for regular treatment monitoring by CD4 counts. SETTINGS AND DESIGN: A longitudinal cohort study on an established cohort of 166 HIV-1-infected Indian individuals. MATERIALS AND METHODS: Study subjects were followed up for the period from January 2002 to November 2006. Their clinical status and treatment regimen were recorded and CD4 counts were performed at each visit. STATISTICAL ANALYSIS: Repeated-measures ANOVA was used to compute changes in median CD4 counts at each visit in the different treatment groups. RESULTS: We observed a growing awareness and motivation for regular HIV disease monitoring among patients, accompanied by a trend of increasing median CD4 counts at all subsequent follow-up visits after initiation of antiretroviral treatment. CONCLUSIONS: The study gives an insight into the institutional efforts for the establishment of cohorts for longitudinal studies, which will help in designing effective treatment guidelines, thus providing impetus to the free public sector antiretroviral therapy program in India. Such formative research aims to fill the lacunae in the limited available data for the formulation of treatment-monitoring guidelines in resource-poor settings of developing countries like India.