Inflammatory Blood Indices Show No Link to Erectile Dysfunction in Young Men with HIV

A cross-sectional study of 308 young men living with HIV has found no significant association between erectile dysfunction and a panel of inflammation-based blood indices, in contrast to what has repeatedly been reported in the general population. The research, conducted at the outpatient HIV clinic of ASST Spedali Civili di Brescia in Italy, is among the first to systematically test whether novel inflammatory and atherogenic indices—ratios derived from routine blood counts and lipids—are linked to erectile dysfunction in this population. The answer, across every analytical approach the investigators applied, was no.

The study enrolled men aged 18 to 50 who were routinely followed at the clinic between January 2023 and January 2024. The upper age limit was chosen deliberately to minimize age-related confounding, since erectile dysfunction becomes steadily more common with advancing age. All eligible patients were systematically screened for erectile dysfunction symptoms during routine follow-up visits, in line with current European AIDS Clinical Society guidelines. Of 358 men screened for eligibility, 24 were excluded because of psychiatric disorders requiring treatment and 26 declined participation, leaving 308 participants in the final analysis.

Erectile dysfunction was defined as any self-reported persistent difficulty in attaining or maintaining an erection, regardless of severity. By this measure, 63 of the 308 participants—20.5 percent—reported the condition, with a mean International Index of Erectile Function-5 score of 13.6 among those affected. The investigators excluded men taking phosphodiesterase type 5 inhibitors, antidepressants, antipsychotics, gonadotropin-releasing hormone analogues, and several other medications that could confound the picture, and also excluded those with current or recent chemotherapy or anticonvulsant use.

The core of the analysis rested on a set of indices that have attracted growing interest as cheap, easily obtainable markers of systemic inflammation and atherogenic risk. These included the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, the platelet-to-neutrophil ratio, the lymphocyte-to-monocyte ratio, the neutrophil-to-lymphocyte-platelet ratio, and the atherogenic index of plasma, calculated as the base-10 logarithm of the ratio between fasting triglycerides and high-density lipoprotein cholesterol. The CD4-to-CD8 ratio, a recognized marker of immunosenescence and immune activation in people living with HIV, was also examined.

Demographic characteristics and viro-immunological parameters were comparable between participants with and without erectile dysfunction, and no statistically significant differences emerged in any of the inflammatory or atherogenic indices between the two groups. Univariate logistic regression models identified no significant associations between erectile dysfunction and any of the indices examined. Multivariate models adjusting for age, total CD4 and CD8 T-cell counts, and a cumulative comorbidity score likewise failed to reveal any predictors of the condition.

The novelty of the study lay in its second analytical layer. Because relationships between inflammatory markers and disease risk are often not linear, the researchers also fitted generalized additive models, which allow flexible, curved relationships rather than forcing a straight-line assumption. These models revealed mildly non-linear trends for the atherogenic index of plasma, the platelet-to-lymphocyte ratio, and the platelet-to-neutrophil ratio, but none of the smooth terms reached statistical significance. Interestingly, the overall additive model fit the data better than the corresponding linear model, with a lower Akaike Information Criterion of 168.9 versus 180.2 and a higher percentage of explained deviance, 14.4 percent versus 7.0 percent. Marginal effect plots, however, showed no consistent or clinically meaningful patterns.

What did differ between the groups was comorbidity burden. Men reporting erectile dysfunction carried a significantly higher load of cardiovascular disease, 25.4 percent versus 13.1 percent; dyslipidaemia, 57.1 percent versus 32.2 percent; and hepatic steatosis, 35.2 percent versus 12.4 percent. Twelve percent of those with erectile dysfunction reported at least three comorbid conditions, compared with seven percent of those without. These differences suggest that in this young cohort, non-inflammatory contributors—metabolic and vascular in particular—may be more relevant to erectile function than circulating immune-cell ratios.

The 20.5 percent prevalence observed here sits well below figures reported in other studies of people living with HIV, which have ranged from 13 to 86 percent and have included recent Italian estimates near 60 percent. The authors note that their figure is comparable to rates from population-based self-reported surveys in the United States, and that self-report may underestimate true prevalence given the well-documented reluctance of patients to discuss sexual health with clinicians. The study’s design also cannot establish causation, and the absence of an HIV-negative comparison group means no direct inferences can be drawn about HIV-specific mechanisms.

Several explanations for the null result are plausible. The cohort was young and largely free of obesity, and the CD4-to-CD8 ratio has been linked to adverse outcomes primarily in older populations. The authors also raise the possibility that high rates of dyslipidaemia combined with guideline-driven statin use in people living with HIV over 40 may have blunted the inflammatory indices, since statins have anti-inflammatory and immunomodulatory actions beyond lipid lowering, although evidence on their effects on these specific indices remains inconsistent. The relatively small number of erectile dysfunction cases—63—may also have limited statistical power and restricted the number of covariates that could be included in the multivariable models without overfitting.

The study had further limitations worth weighing. Erectile dysfunction was assessed by self-report rather than a validated questionnaire, introducing potential misclassification, and no data were collected on hormonal status, psychological or sexual health factors, partner characteristics, or concomitant medications beyond the exclusion criteria. Residual confounding cannot be excluded, and the single-center design limits generalizability. No formal sample size calculation was performed, as the study was designed as an exploratory pilot. The authors conclude that erectile dysfunction in young men living with well-controlled HIV may be driven substantially by non-inflammatory mechanisms, including psychological and functional factors, and they argue for a multidisciplinary approach that includes andrological evaluation rather than reliance on inflammation-based blood markers alone.

Subject of Research: Inflammatory blood indices and erectile dysfunction in young men living with HIV

Article Title: Non-linear relationships between inflammatory indices and erectile dysfunction in a group of young men living with HIV

Article References: Tiecco, G., Riva, M., Cesanelli, F., Rossi, L., Colangelo, C., Reale, S. A., Gottardi, F., Delbarba, A., Cappelli, C., Focà, E., Castelli, F., & Quiros-Roldan, E. (2026). Non-linear relationships between inflammatory indices and erectile dysfunction in a group of young men living with HIV. Basic and Clinical Andrology, 36(1), Article 18. https://doi.org/10.1186/s12610-026-00320-6

Image Credits: AI Generated

DOI: 10.1186/s12610-026-00320-6

Keywords: erectile dysfunction, HIV, inflammatory indices, cross-sectional study, atherogenic index of plasma, CD4/CD8 ratio, comorbidities, young men, immune activation, generalized additive models, dyslipidaemia, single-center study