Immune reconstitution inflammatory syndrome (IRIS) occurs in up to 40% of individuals co-infected with pulmonary tuberculosis (PTB) and HIV, primarily upon antiretroviral therapy (ART) initiation. Phenotypic changes in T-cells during TB-IRIS and their relationship with systemic inflammation are not fully understood. In this prospective cohort study, we followed 48 HIV-positive patients with PTB from South India before and after ART initiation, examining T-lymphocyte subsets and inflammatory biomarkers in peripheral blood. Quantification of naïve (CD27+CD45RO−) as well as effector memory CD4+ T cells (CD27−CD45RO+) at weeks 2–6 after ART initiation could distinguish TB-IRIS from non-IRIS individuals. Additional analyses revealed that ART reconstituted different quantities of CD4+ T lymphocyte subsets with preferential expansion of CXCR3+ CCR6− cells in TB-IRIS patients. Moreover, there was an expansion and functional restoration of central memory (CD27+CD45RO+) CXCR3+CCR6− CD4+ lymphocytes and corresponding cytokines, with reduction in CXCR3−CCR6+ cells after ART initiation only in those who developed TB-IRIS. Together, these observations trace a detailed picture of CD4+ T cell subsets tightly associated with IRIS, which may serve as targets for prophylactic and/or therapeutic interventions in the future.

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T cells play an important role in controlling viral replication during HIV infection. An effective vaccine should, therefore, lead to the induction of a strong and early viral-specific CD8 + T cell response. While polyfunctional T cell responses are thought to be important contributors to the antiviral response, there is evidence to show that polyfunctional HIV-specific CD8 + T cells are just a small fraction of the total HIV-specific CD8 + T cells and may be absent in many individuals who control HIV replication, suggesting that other HIV-1 specific CD8 + effector T cell subsets may be key players in HIV control. Stem cell-like memory T cells (T SCM) are a subset of T cells with a long half-life and self-renewal capacity. They serve as key reservoirs for HIV and contribute a significant barrier to HIV eradication. The present study evaluated vaccineinduced antiviral responses and T SCM cells in volunteers vaccinated with a subtype C prophylactic HIV-1 vaccine candidate administered in a prime-boost regimen. We found that ADVAX DNA prime followed by MVA boost induced significantly more peripheral CD8 + T SCM cells and higher levels of CD8 + T cell-mediated inhibition of replication of different HIV-1 clades as compared to MVA alone and placebo. These findings are novel and provide encouraging evidence to demonstrate the induction of T SCM and cytotoxic immune responses by a subtype C HIV-1 prophylactic vaccine administered using a prime-boost strategy.

Background and Objectives:A variety of demographic factors, sex, and degree of immunosuppression can influence antiretroviral drug concentrations. The authors studied the influence of immune status, sex, and body mass index (BMI) on the steady-state pharmacokinetics of nevirapine delivered as a fixed-dose combination in HIV-1-infected patients in India. Methods: Twenty-six HIV-1-infected adult patients undergoing treatment with nevirapine-based highly active antiretroviral therapy regimens participated in the study. Pharmacokinetic variables were compared between patients divided based on CD4 cell counts, sex, and BMI. Results: Patients with higher BMI had lower peak and trough concentration and exposure of nevirapine than those with lower BMI; none of the differences in the pharmacokinetic variables of nevirapine between the various patient groups was statistically significant. Conclusions: Patients' immune status, sex, or BMI had no impact on the pharmacokinetics of nevirapine. Plasma nevirapine concentrations were maintained within the therapeutic range of the drug in the majority of the patients.Keywords: pharmacokinetics; nevirapine; India; immune status; sex; BMI Access to antiretroviral drugs for HIV-1-infected patients in developing countries is a global public health priority. The World Health Organization currently recommends first-line therapy with 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-NRTI (NNRTI)⎯a combination with good efficacy, tolerability, simplicity, and low cost. 1 Generic fixed-dose combinations (FDCs) of such regimens are widely regarded as crucial for scaling up AIDS treatment in developing countries. Two triple-drug combinations consisting of nevirapine and lamivudine with either stavudine or zidovudine as the third agent are available as FDCs in the developing world. A vast majority of HIV-infected patients in India receive nevirapine-based highly active antiretroviral therapy (HAART), the common co-drugs being lamivudine and stavudine. 2 A few studies have reported the effectiveness and safety of generic FDCs for treatment of HIV-1-infected adults. [2][3][4][5] It has been suggested that a variety of demographic factors such as age, body size, and weight can influence antiretroviral drug concentrations. 6 Sex-based differences in the pharmacokinetics of nevirapine have also been observed. 7 Keating et al reported that malabsorption correlates significantly with the degree of immunosuppression. 8 We undertook a study to obtain information on the pharmacokinetics of nevirapine in HIV-infected patients on treatment with FDCs in India, as well as the influence of immunological status, sex, and body mass index (BMI) on the pharmacokinetics of these drugs, as very limited information is available on this aspect. Methods PatientsThe study participants were composed of HIV-infected patients of ethnic Indian origin who were participating in a controlled clinical trial and were being followed