Sex Differences in HIV Infection

Altfeld, Marcus; Scully, Eileen P.

doi:10.1007/978-3-031-35139-6_3

Cited by 3 publications

(3 citation statements)

References 87 publications

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“…Similarly, female PLWH1 have been suggested to have a lower set-point pVL compared to male PLWH1. 96 However, while findings from our cohort, and others, suggest that female PLWH2 progress slower to AIDS compared to male PLWH2, 3 , 97 the same has not been observed among female PLWH1. The underlying mechanisms behind the difference in disease progression rate associated with sex, in a HIV type-dependent manner, is not known, but could potentially be explained by the fact that females mount stronger type I interferon responses compared to males at matched HIV-1 pVL.…”

Section: Discussioncontrasting

confidence: 48%

“…The underlying mechanisms behind the difference in disease progression rate associated with sex, in a HIV type-dependent manner, is not known, but could potentially be explained by the fact that females mount stronger type I interferon responses compared to males at matched HIV-1 pVL. 96 While the high pVL of PLWH1 has been suggested to lead to increased immunopathology among female PLWH1 compared to male PLWH1 at matched pVL levels, 96 it is possible that the naturally low to undetectable pVL of PLWH2 provides an advantage for female PLWH2. This could be explained both by the fact that HIV-2 has been shown to be more interferon-sensitive than HIV-1, and that the increased induction of type I interferon responses by HIV-2 has been suggested to result in an improved priming of HIV-specific CD8 + T-cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

Johansson,

Nazziwa,

Freyhult

et al. 2024

iScience

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

Johansson,

Nazziwa,

Freyhult

et al. 2024

iScience

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“…The finding that detectable HIV-DNA in CSF cells was associated with male sex at birth and lower CD4 + cell count at enrollment should be evaluated in larger studies, particularly given previously described sex differences in HIV pathogenesis and persistence. These include higher type I interferon responses and lower viral loads in untreated infection, with increased residual immune activation yet decreased residual viremia and cell-associated HIV-RNA levels during ART in women [ 61 ]. How these differences influence CSF HIV-DNA in men and women is not known.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy

Wagner,

Tierney,

Huang

et al. 2024

Aids

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Objective: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). Design: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. Methods: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) > 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIVpol/gag-DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. Results: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. 9/18 (50%) were female sex-at-birth, 14/18 (78%) were Black. Median (range) age was 20 years (13–27), time on ART 18.3 years (8.0–25.5), and FCCS 68 (53–80). HIV-DNA was detected in PBMCs from all participants. In CSF, 2/18 (11%, 95% CI: 1.4–34.7%) participants had detectable cell-free HIV-RNA, while HIVgag or pol-DNA was detectable in 13/18 (72%, 95% CI: 47–90%). Detectable HIV-DNA in CSF was associated with male sex-at-birth (p = 0.051), lower CD4 count at enrollment (p = 0.016), and higher PBMC HIVpol-DNA copies (p = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. Conclusions: We found a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

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Attenuation of HIV-specific T cell responses Among people with HIV on ART following dipyridamole treatment

Morris,

Hixson,

Klamar-Blain

et al. 2024

Journal of Leukocyte Biology

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Twelve weeks of dipyridamole increased extracellular adenosine levels and decreased T cell activation in people with human immunodeficiency virus (HIV). In this analysis, we investigated the effect of dipyridamole on HIV-specific T cell responses. We compared changes in Gag- and Env-specific T cell responses using intracellular cytokine staining, following 12 wk of dipyridamole treatment vs placebo. We evaluated whether frequencies of polyfunctional HIV-specific T cells were associated with purines in the adenosine pathway and with measures of HIV persistence and chronic inflammation. There was a significant decrease in CD4+ polyfunctional T cell responses to Gag (−62.6% vs −23.0%; P < 0.001) and Env (−56.1% vs −6.0%; P < 0.001) in the dipyridamole arm. In the dipyridamole group, lower frequencies of polyfunctional Env-specific CD4+ T cells were associated with higher plasma levels of adenosine (r = −0.85, P < 0.01) and inosine (r = −0.70, P = 0.04). Higher adenosine levels induced by dipyridamole treatment is associated with decreased HIV-specific CD4+ T cell polyfunctional responses in people with HIV on antiretroviral therapy.

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Sex Differences in HIV Infection

Cited by 3 publications

References 87 publications

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy

Attenuation of HIV-specific T cell responses Among people with HIV on ART following dipyridamole treatment

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