Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study.

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.

Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening.

The evolution of clinical study design in heavily treatment-experienced persons with HIV: A critical review.

Heavily treatment-experienced (HTE) persons with HIV have limited options for antiretroviral therapy and face many challenges, complicating their disease management. There is an ongoing need for new antiretrovirals and treatment strategies for this population. We reviewed the study designs, baseline characteristics, and results of clinical trials that enrolled HTE persons with HIV.

Dolutegravir-based regimens in treatment-naive and treatment-experienced aging populations: analyses of 6 phase III clinical trials.

Older adults living with HIV (OALWH) are a growing population facing unique challenges to successful antiretroviral therapy. To assess efficacy and safety profiles of antiretroviral regimens, including those containing dolutegravir, in OALWH. Combined data from 6 phase III/IIIb trials in treatment-naive (ARIA, FLAMINGO, SINGLE, SPRING-2;  = 2634) and treatment-experienced (DAWNING, SAILING;  = 1339) participants receiving dolutegravir- or non-dolutegravir-based regimens were analyzed by age (<50, ≥50 to <65, and ≥65 years).

Morbidity in older HIV-infected patients: impact of long-term antiretroviral use.

The introduction of HAART has represented a major advance in the care of people with HIV. By markedly increasing life expectancy, HAART has significantly changed the pattern of HIV infection in developed countries, the "graying" of the HIV-infected population being a powerful testament to its success. However, this has presented physicians with new challenges relating to the care of older patients with HIV, many of whom exhibit a "frailty syndrome" associated with increased comorbidity and chronic low-grade inflammation in a process which has recently been termed "inflammaging".

Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial.

Low levels of vitamin D are reported in HIV-infected individuals. In HIV-negative people, low vitamin D levels have been associated with an increased risk of cardiovascular disease and cancer and with worse survival. The MONET trial recruited 256 European patients with HIV RNA <50 copies/ml at screening, while taking either NNRTI- or PI-based HAART.

Ex vivo analysis of HIV-1 co-receptors at the endocervical mucosa of women using oral contraceptives.

Combined oral contraceptives may alter the microenvironment of the female genital tract and, thus, influence susceptibility of endocervical cells to HIV-1 transmission. The mechanism for this effect is unknown but might involve combined oral contraceptive up-regulation of chemokine receptors on CD4+ endocervical cells. We measured chemokine co-receptor (CCR5 and CXCR4) expression on cervical intraepithelial CD4+ T lymphocytes, macrophages and dendritic cells using flow cytometry in 32 healthy women, 16 of whom were combined oral contraceptive users and 16 non-users.

Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis.

Presence of early secretory antigenic target-6 (ESAT-6)-specific, interferon- gamma -secreting T cells in blood accurately marks tuberculosis infection. In tuberculous pleural effusions from 10 patients with tuberculosis, these cells were concentrated a mean of 15-fold (standard deviation, +/-6-fold), relative to their level in peripheral blood (P=.014), and displayed rapid effector function.

Chemokine receptor expression on mucosal dendritic cells from the endocervix of healthy women.

Dendritic cells (DCs) may be an initial target of human immunodeficiency virus (HIV) during heterosexual transmission. An analysis of DCs in the intraepithelial layer of the endocervix of the female genital tract from healthy women showed that ~20% expressed CD1a, and 30% expressed cutaneous leukocyte antigen (CLA). Langerin, a molecule associated with Langerhans DCs, was on CD1a-positive and -negative DCs and on CLA-positive cells.

Recruitment of CD4 T lymphocytes and macrophages into the cervical epithelium of women after coitus.

Objective: T lymphocytes and macrophages are considered essential components of the immune response. Many factors are known to influence the presence and distribution these cells in genital mucosa. This study investigated the effect of sexual intercourse on cervical intraepithelial T lymphocytes and macrophages in healthy uninfected women.

Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women.

Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the predominant mode of infection worldwide. Increased risk of HIV-1 transmission has been reported with oral contraceptive use. To elucidate the underlying mechanism of this observation, intraepithelial endocervical T lymphocytes from women using oral contraceptives were analysed for expression of activation and chemokine receptors.