Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection.

OBJECTIVE: AIDS-defining illness develops at higher CD4 + T-cell counts in individuals infected with HIV-2 compared with HIV-1-infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types. DESIGN: Cross-sectional. METHODS: ART-naive HIV-1 ( n  = 83), HIV-2 ( n  = 63), and HIV-1/2 dually positive ( n  = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls ( n  = 26). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206. RESULTS: Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 + cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants. CONCLUSION: The monocyte phenotype of HIV-2-positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2-positive participants also had a lower concentration of extracellular CD206 vesicles compared with HIV-1-positive participants. This does not explain the difference in AIDS development.

Acceptance and Feasibility of Partner Notification to HIV Infected Individuals in Guinea-Bissau.

As partner notification (PN) has shown effective in increasing the number of partners of HIV infected patients being tested we aimed to evaluate the feasibility of implementing PN in the West-African country Guinea-Bissau. Patients enrolled were offered the choice of three different PN methods. Acceptance, successful referrals and HIV status of partners were evaluated. Of 697 patients offered PN, 495 (71.0%) accepted and listed 547 partners. At end of follow-up 118 (21.5%) partners had been tested of which 44 (37.3%) were HIV infected. HIV infected partners had a higher median CD4 count at diagnosis compared with index patients; 401 cells/mm3 versus 240 cells/mm3, p < 0.001. The results indicate that implementation of PN is feasible, effective in identifying HIV infected partners and enables initiation of earlier treatment, yet there are major barriers to bringing partners in for testing which should be addressed in order to exploit the full potential of PN.

T-cell and B-cell perturbations are similar in ART-naive HIV-1 and HIV-1/2 dually infected patients.

BACKGROUND: HIV-2 may slow progression of a subsequently acquired HIV-1 infection through cross-neutralizing antibodies and polyfunctional CD8 T cells. We hypothesized that HIV-1/2 dually infected patients compared with HIV-1-infected patients had more preserved immune maturation subsets and less immune activation of T and B cells. METHODS: ART-naive patients with HIV-1 (n = 83) or HIV-1/2 dual (n = 27) infections were included in this cross-sectional study at an HIV clinic in Guinea-Bissau. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry according to T-cell maturation and activation, regulatory T-cell fraction, and B-cell maturation and activation. RESULTS: HIV-1/2 dually infected patients had lower levels of HIV-1 RNA compared with patients with HIV-1 infection, but the levels of total HIV RNA (HIV-1 and HIV-2) were similar in the two patient groups. T-cell maturation, and proportions of regulatory T cells (FoxP3+) were also similar in the two groups. HIV-1/2 dually infected patients had higher proportions of CD4 and CD8 T cells positive for the activation marker CD38, but there was no difference in other T-cell activation markers (CD28, CTLA-4, PD-1). HIV-1/2 dually infected patients also had higher proportions of IgM-only B cells and plasmablasts. CONCLUSION: HIV-1/2 was not associated with less immune perturbations than for HIV-1 infection.

T-cell and B-cell perturbations identify distinct differences in HIV-2 compared with HIV-1-induced immunodeficiency.

BACKGROUND: For unknown reasons, HIV-2 is less pathogenic than HIV-1, and HIV-2-induced immunodeficiency may be different from that caused by HIV-1. Previous immunological studies have hinted at possible shifts in both T-cell and B-cell subsets, which we aimed to characterize further. METHODS: From an HIV clinic in Guinea-Bissau, 63 HIV-2, 83 HIV-1, and 26 HIV-negative participants were included. All HIV-infected participants were ART-naive. The following cell subsets were analysed by flow cytometry; T cells (maturation and activation), regulatory T cells, and B cells (maturation and activation). RESULTS: After standardizing for sex, age, and CD4 T-cell count HIV-2 had 0.938 log10 copies/ml lower HIV RNA levels than the HIV-1-infected patients. Whereas T-cell maturation and regulatory T-cell profiles were similar between patients, HIV-2-infected patients had higher proportions of CD8CD28 and lower proportions of CD8PD-1+ T cells than HIV-1-infected patients. This finding was independent of HIV RNA levels. HIV-2 was also associated with a more preserved proportion of naive B cells. CONCLUSION: HIV-2 is characterized by lower viral load, and lower T-cell activation, which may account for the slower disease progression.