We genotyped the RT and PI regions of the pol gene of HIV-1 from treatment-naive infected individuals in North India and evaluated their possible physiological relevance and association with drug resistance. Plasma samples from 52 newly diagnosed HIV-1-infected drug-naive individuals were subjected to CD4(+) cell count and plasma viral load. For genotyping, the protease and RT regions of the pol gene were amplified from cDNA reverse transcribed from plasma viral RNA by single or nested polymerase chain reaction (PCR). Sequences of amplified products were analyzed for mutations using the Stanford DR and REGA database. Two out of 49 amplicons showed mutations at known "major" subtype B drug resistance positions (one each in protease and RT). In the protease region it showed a major drug resistance mutation at M46I as well as "minor" positions F53L and T74P. In the RT gene, one patient showed a mutation at major NNRTI position G190V. Forty-nine percent had mutations in the hinge (M36I, R41K, H69K) and alpha-helix (L89M) regions of the C-virus protease, which has been linked to increased catalytic activity. Our study indicates that a number of major mutations associated with resistance to PIs, NNRTIs, and NRTIs do exist, though at a low frequency, among HIV-1 isolates from treatment-naive individuals in North India. Many minor or accessory mutations related to resistance to PIs and NRTIs are also present as the variants. These results point to the greater biochemical fitness of subtype C protease and faster decrease in drug sensitivity.

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Activation of NF-κB has been reported to play a key role in causing endotoxin-induced hepatic damage through enhanced production of reactive oxygen species and pro-inflammatory mediators. In this context, the potential of polyphenolic phytochemicals in preventing endotoxin-induced liver damage remains unclear. Here, we demonstrate that catechin and quercetin have the potential to down-regulate the initial signalling molecule NF-κB which may further inhibit the downstream cascade including TNF-α and NO. These results were confirmed using N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of inducible nitric oxide synthase (iNOS) along with the biochemical and histological alterations occurring in the presence and absence of supplementation with both the polyphenols. However, catechin was found to be more effective than quercetin against endotoxin-induced liver injury. These findings suggest that these polyphenols may form a pharmacological basis for designing a therapeutic agent against endotoxin-mediated oxidative damage.

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Understanding of the chronic immune activation, breakdown of immune defense and synergistic effect between HIV and Mycobacterium tuberculosis (Mtb) may provide essential information regarding key factors involved in the pathogenesis of HIV disease. In this study, we aimed to highlight a few of the immunological events that may influence and accelerate the progression of HIV disease in the presence of co-infecting Mtb. A cross-sectional study was performed on cohorts, including anti-tubercular therapy (ATT) naïve active pulmonary tuberculosis (PTB) patients, antiretroviral therapy (ART) naïve HIV-1 infected individuals at different stages of disease, ATT and ART naïve HIV-PTB co-infected individuals and healthy controls. A significantly higher T-regulatory cell (Treg) frequency coupled with the high FoxP3 expression in the CD4 T-cells indicated an immunosuppressive environment in the advance stage of HIV-1 infection. This is further substantiated by high HO-1 expression favoring TB co-infection. Functionally, this change in Treg frequency in HIV-1 infected individuals correlated well with suppression of T-cell proliferation. Mtb infection seems to facilitate the expansion of the Treg pool along with increased expression of FoxP3, specifically the variant-1, as evident from the data in HIV-1 co-infected as well as in patients with only PTB. A significantly lower expression of HO-1 in co-infected individuals compared to patients with only HIV-infection having comparable CD4 count correlated well with increased expression of CCR5 and CxCR4 as well as NF-κB and inflammatory cytokines IL-6 and TNF-α, which collectively may contribute to enhanced viral replication and increased cell death, hence faster disease progression in co-infected individuals.