# Alteration in the hypothalamic-pituitary-gonadal axis and frailty in aging men with HIV

> **NIH NIH K01** · JOHNS HOPKINS UNIVERSITY · 2022 · $130,140

## Abstract

PROJECT SUMMARY/ABSTRACT People with human immunodeficiency virus (HIV), (PWH), are at increased
risk of frailty, which increases the risk of adverse age-related outcomes, including falls, hospitalization and
mortality. The mechanisms of frailty are not completely understood, particularly among PWH. The objectives of
this proposal are to study the extent to which free testosterone and sex hormone binging globulin (SHBG)
concentrations are associated with frailty and inflammation in men with HIV. We hypothesize that free
testosterone and SHBG are key biomarkers for identifying PWH at the highest risk of frailty and who may
benefit from intervention with anabolic agents. Our specific aims are to: 1) Determine the association of
circulating free testosterone and SHBG with incident frailty using state-of-the-art hormone measurements among
men with HIV, 2) Determine the association of diurnal variation in free testosterone with HIV serostatus in men
and its association with systemic inflammation, 3) Determine the association of novel SHBG glycans with frailty
among men with HIV.
In Aim 1, we will measure serum free testosterone with state-of-the-art methods and SHBG in men with HIV
who are part of the Multicenter AIDS Cohort Study (MACS), an ongoing prospective study since 1984 studying
the natural and treated histories of HIV-1 infection in homosexual and bisexual men. We will determine the
associations of these hormones with incident frailty, collected at semi-annual visits since 2007.
In Aim 2, we will select men with and without HIV that have collected blood samples in AM and PM to assess
diurnal variation in free testosterone and systemic inflammation [Interleukin 6 (IL6) and soluble TNF-alpha
receptors II (sTNFRII)].
In Aim 3, we will study novel SHBG glycoforms in men with HIV, the identification and quantification of SHBG
glycoforms will be performed by capillary electrophoresis and lectin microarray. The proposed research aims to
provide new insights to the contribution of free testosterone and SHBG in frailty and its relationship with systemic
inflammation. The goals during the award period include gaining advanced expertise in biostatistical methods,
design and conduct epidemiological studies, as well as hands-on experience in the measurement of glycoforms
from plasma proteins and interpretation of glycomic data through mentored research, tailored didactic
coursework, and supervised performance of relevant laboratory techniques. Long-term goals include developing
a career as an independent investigator in translational epidemiology and developing new approaches to treating
and preventing age-related outcomes such as frailty in PWH.

## Key facts

- **NIH application ID:** 10545981
- **Project number:** 1K01AG079680-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jenny Pena Dias
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $130,140
- **Award type:** 1
- **Project period:** 2022-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545981

## Citation

> US National Institutes of Health, RePORTER application 10545981, Alteration in the hypothalamic-pituitary-gonadal axis and frailty in aging men with HIV (1K01AG079680-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10545981. Licensed CC0.

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