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Introduction: Human pegivirus-1 (HPgV-1) influences the pathogenesis and outcome of viral infections. We investigated the prevalence and impact of HPgV-1 due to the paucity of studies on Indian people living with HIV (PLHIV)., Methodology: Samples were collected from 347 treatment-naïve PLHIV; and 100 blood donors negative for HIV, HBV, and HCV. CD4+ T-cell and HIV-1 viral load were measured using flow-cytometry and quantitative polymerase chain reaction (qPCR), respectively. HPgV-1 was quantified and genotyped by qPCR and Sanger sequencing, respectively., Results: HPgV-1 viremia in PLHIV and controls was 11% (38/347) and 1% (1/100), respectively. We found HPgV-1 genotype-2a in PLHIV and genotype-2b in controls. Male preponderance was seen in HIV-1 mono-infection and co-infection groups (166 vs. 143 and 33 vs. 5; p < 0.0001). The peak prevalence of HPgV-1 was at 31-50 years (p = 0.02). CD4+ T-cell count (245.5 vs. 240; p = 0.59) and HIV-1 log viral load (4.7 vs. 4.9; p = 0.50) were not significantly different between the HIV-1 mono-infected and coinfected individuals. However, a direct correlation existed between HpgV-1 viral load and CD4+ T-cell count (r = 0.27, p = 0.05) and an inverse correlation with HIV-1 viral load (r = -0.21, p = 0.10)., Conclusions: This is the first study in India to estimate the HPgV-1 prevalence in PLHIV with the predominance of genotype-2a. HPgV-1 viremia had a moderate impact on CD4+ T-cells and HIV-1 viral load, which requires a longitudinal study to identify the beneficial influence on HIV-1 disease progression and outcome., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Diviya Alex, Runal J Steve, Veena V Ramalingam, John P Demosthenes, Gopinathan Vijayalakshmi, Ben C Ghale, Priscilla Rupali, George M Varghese, Dolly Daniel, Grace Rebekah, Gnanadurai J Fletcher, Priya Abraham, Rajesh Kannangai.)

Background: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV., Methods: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV&HBV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV., Results: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups., Conclusion: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Using computer modeling of three-dimensional structures and structural information available on the crystal structures of HIV-1 protease, we investigated the structural effects of mutations, in treatment-naive and treatment-exposed individuals from India and postulated mechanisms of resistance in clade C variants. A large number of models (14) have been generated by computational mutation of the available crystal structures of drug bound proteases. Localized energy minimization was carried out in and around the sites of mutation in order to optimize the geometry of interactions present. Most of the mutations result in structural differences at the flap that favors the semiopen state of the enzyme. Some of the mutations were also found to confer resistance by affecting the geometry of the active site. The E35D mutation affects the flap structure in clade B strains and E35N and E35K mutation, seen in our modeled strains, have a more profound effect. Common polymorphisms at positions 36 and 63 in clade C also affected flap structure. Apart from a few other residues Gln-58, Asn-83, Asn-88, and Gln-92 and their interactions are important for the transition from the closed to the open state. Development of protease inhibitors by structure-based design requires investigation of mechanisms operative for clade C to improve the efficacy of therapy.

Background and Objective: HIV-1 uses co-receptors CCR5 and CXCR4 in addition to CD4 for viral entry into cells. CCR5 is used in the early stages of HIV-1 infection, but viruses that utilize CXCR4 for viral entry emerge in the later stages. This is not common among clade C strains, with previous data from India showing the absence of the emergence of CXCR4-using strains. Sequence analysis has demonstrated that the V3 loop plays a very important role in determining the syncytium-inducing (SI) phenotype. The V3 region of the SI variants were observed to have positively charged amino acids at positions 11 and/or 25 and also a overall higher charge. This study looked at co-receptor usage among HIV-1 strains in India from individuals who were antiretroviral therapy (ART) naïve and those not responding to ART., Methods: Amplification and sequencing of the HIV-1 env gp120 V3 region was done on 40 ART-naïve individuals, who were selected for the study based on their CD4 counts, and eight patients who had not responded to ART. The sequences were submitted to Geno2Pheno and Web PSSM. The pol gene sequences of these strains were submitted to the REGA HIV-1 subtyping tool., Results: Forty-seven strains were identified as clade C and one strain as clade A1. Geno2Pheno identified three CXCR4-using strains, and the Web PSSM clade C matrix identified two., Conclusion: We report, for the first time, CXCR4-using strains among HIV-1 clade C strains circulating in India.

Background & Objective: Individuals infected with HIV-1 have higher levels of chemokine producing cells compared to uninfected individuals. It is important to know the changes in chemokine levels associated with rate of progression of disease. There is a paucity of information on the plasma chemokines in HIV-1 infected individuals from India. We therefore carried out this study to estimate the levels of three chemokines namely macrophage inflammatory protein alpha (MIP1alpha), MIP1beta and RANTES, in relation to disease status in HIV-1 infected individuals and compared with uninfected individuals., Methods: RANTES and MIP1alpha were estimated using ELISA in 114 HIV-1 infected and 30 controls, whereas MIP1beta was estimated in 101 HIV infected individuals only and 30 controls. The values were compared to the T cell subsets, HIV-1 viral loads and plasma cytokines (interferon gamma and interleukin-10)., Results: Compared to controls the mean MIP1alpha and RANTES level among the HIV-1 infected individuals was higher while MIP1beta level was lower in HIV infected individuals except CDC C groups. There was a significant positive correlation for MIP1á with HIV-1 viral load and IFNgamma, for MIP1alpha with viral load and IL10. There was a significant negative correlation between MIP1alpha with CD4 count and CD4: CD8 ratio and MIP1beta with CD4 count and CD8 count. There was a negativecorrelation between RANTES values and CD8 per cent., Interpretation & Conclusion: In conclusion, our study showed a significantly higher level of beta chemokines in south Indian HIV-1 infected individuals compared to controls. These beta chemokines may have the inhibitory effect on HIV-1 only during the initial period and with the progression of disease this inhibitory effect wanes as shown by the positive correlation of beta chemokines with HIV-1 viral load.

Background & objectives: Apoptosis causes a decline in the counts of uninfected bystander CD4+ T cells in HIV infection. The rate of disease progression of HIV infection is considered to be faster in the developing countries. The present study was carried out to investigate certain markers for apoptosis in immunopathogensis of disease in HIV infected south Indian population. Methods: Soluble Fas (sFas) antigen and Fas ligand levels in plasma samples from 39 antiretroviral treatment naïve patients was estimated and compared with T cell subsets and HIV-1 viral load. Results: The mean sFas antigen levels among controls and the CDC A, B and C clinical stages were 2.77, 3.08, 3.26 and 3.28 ng /ml respectively, higher though not significantly among HIV-1 infected individuals compared to controls. The mean sFas ligand levels in CDC A, B and C stages were 0.138, 0.125 and 0.117 ng/ml respectively were higher (P<0.001) than controls (0.073 ng/ml) and positively correlated with total lymphocyte % (r=0.43, P =0.007). sFas antigen levels were negatively correlated with total WBC count (r=-0.34, P=0.04), CD4% (r=-0.4, P=0.01) and CD4:CD8 ratio (r=-0.37, P=0.02). There was an increase in plasma levels of sFas antigen and Fas ligand over time in asymptomatics. Interpretation & conclusions: The high levels of sFas antigen and Fas ligand seen in HIV infected individuals suggest increased activation and apoptosis of T cells, due to constant stimulation of the immune system by inter-current infections of HIV infected individuals in south India. [ABSTRACT FROM AUTHOR]