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The performance of a rapid particle agglutination test for human immunodeficiency virus (HIV) (Capillus HIV type 1 [HIV-1]/HIV-2) on hospital samples is compared with enzyme-linked immunosorbent assays. The test had a sensitivity and specificity of 99 and 98.9%, respectively. In addition, the test was reactive on plasma samples from all individuals infected with HIV-1 subtype C. This test can safely be used for voluntary counseling and testing in India.

BACKGROUND: An important aspect of ensuring blood safety is the performance of mandatory serological testing for transfusion transmissible infections. The practice of internal quality control (IQC) in blood banks in India is nonuniform, especially the use of third-party materials. Cited reasons are cost, lack of access to control materials, and need for deep-freezers for storage, if prepared in-house. OBJECTIVE: Validation of dried tube specimen (DTS) from HIV-positive plasma as a low-cost, stable material for use as IQC material in blood banks. METHODS: Fresh-frozen plasma (FFP) prepared from four HIV-positive blood-donors were pooled. Equal numbers of seronegative FFPs were pooled. Twenty microlitre aliquots of plasma were made in micro-centrifuge tubes and air-dried overnight at room-temperature. These were stored in 2–8°C refrigerators and tested once weekly for 6 months on multiple platforms with different detection principles: Rapid tests, second-generation enzyme-linked immunosorbent assay (ELISA), fourth-generation ELISA, and fourth-generation Chemiluminescence immunoassay. The protocol was sustained over the next 6 months with decreased testing frequency to study the extended stability of DTS. RESULTS: A total of 139 positive-DTS and 139 negative-DTS were tested with 100% samples showing consistent results on all platforms over 1 year. There was mild deterioration in reaction strengths, which did not interfere in result interpretations. CONCLUSION: Plasma in form of DTS maintained stability when stored at 2–8°C for 1 year. This provides evidence that DTS can be a modality for the production of cost-effective, stable, in-house control material for resource-restricted countries. [ABSTRACT FROM AUTHOR]

Transplantation of allogenic hematopoietic stem and progenitor cells (HSPCs) with C-C chemokine receptor type 5 (CCR5) Δ32 genotype generates HIV-1 resistant immune cells. CCR5 gene edited autologous HSPCs can be a potential alternative to hematopoietic stem cell transplantation (HSCT) from HLA-matched CCR5 null donor. However, the clinical application of gene edited autologous HSPCs is critically limited by the quality of the graft, as HIV also infects the HSPCs. In this study, by using mobilized HSPCs from healthy donors, we show that the CD34+CD90+ hematopoietic stem cells (HSCs) express 7-fold lower CD4/CCR5 HIV receptors, higher levels of SAMHD1 anti-viral restriction factor, and possess lower susceptibility to HIV infection than the CD34+CD90- hematopoietic progenitor cells. Further, the treatment with small molecule cocktail of Resveratrol, UM729 and SR1(RUS) improved the in vivo engraftment potential of CD34+CD90+ HSCs. To demonstrate that CD34+CD90+ HSC population as an ideal graft for HIV gene therapy, we sort purified CD34+CD90+ HSCs, treated with RUS and then gene edited the CCR5 with single sgRNA. On transplantation, 100,000 CD34+CD90+ HSCs were sufficient for long-term repopulation of the entire bone marrow of NBSGW mice. Importantly, the gene editing efficiency of ~90% in the infused product was maintained in vivo , facilitating the generation of CCR5 null immune cells, resistant to HIV infection. Altogether, CCR5 gene editing of CD34+CD90+ HSCs provide an ideal gene manipulation strategy for autologous HSCT based gene therapy for HIV infection. [ABSTRACT FROM AUTHOR]

Background & objectives: 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 (MIP1α), MIP1β and RANTES, in relation to disease status in HIV-1 infected individuals and compared with uninfected individuals. Methods: RANTES and MIP1α were estimated using ELISA in 114 HIV-1 infected and 30 controls, whereas MIP1β 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 MIP1α and RANTES level among the HIV-1 infected individuals was higher while MIP1β 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 IFNγ, for MIP1α with viral load and IL10. There was a significant negative correlation between MIP1 a with CD4 count and CD4: CD8 ratio and MIP1 b with CD4 count and CD8 count. There was a negative correlation between RANTES values and CD8 per cent. Interpretation & conclusions: In conclusion, our study showed a significantly higher level of b chemokines in south Indian HIV-1 infected individuals compared to controls. These b 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 b chemokines with HIV-1 viral load. [ABSTRACT FROM AUTHOR]

• Symptomatic HIV CNS viral escape presents as a global cerebral syndrome in treatment experienced patients. • Atazanavir and Tenofovir may be associated with CNS viral escape due to poor CNS penetration. • CNS viral escape produces a CD8 predominant inflammation in the CNS. • Appropriate change of cART improves symptoms in most patients. The clinical syndrome in symptomatic HIV associated CNS viral escape is poorly defined. We attempted to describe the clinical syndrome, laboratory profile, radiological features and outcomes of HIV infected patients with symptomatic central nervous system (CNS) viral escape in our study. This is a retrospective study were adult patients with HIV infection on cART admitted with a diagnosis of CD8 encephalitis or CNS viral escape in a large teaching hospital in South India was identified. The mean age of the eleven patients included in the study was 37.5 years. Most patients had received almost a decade of antiretroviral treatment at diagnosis (mean: 11.18 years). All patients presented with global cerebral syndrome. Cognitive decline, tremors, and headaches were common manifestations. All patients had lymphocytic pleocytosis (mean cell count: 44.63 cells/ml; lymphocyte percentage: 94.81%) with elevated protein (mean: 125.36 mg/dl). All patients were on boosted protease inhibitors (81.8% on Atazanavir and 18.18% Lopinavir). All except one patient was on Tenofovir and lamivudine combination therapy. White matter changes and deep brain nuclei involvement were common. Most patients required a change of cART to regimens with better CNS penetration and suppression of the resistant virus in the plasma and improved. CNS viral escape should be considered as a differential among patients on Atazanavir presenting with non-focal cerebral syndrome and CSF lymphocytic pleocytosis. [ABSTRACT FROM AUTHOR]