Association Between HIV Symptom Burden and Inflammatory Cytokines: An Analysis by Sex and Menopause Stage

Introduction: There is a growing body of knowledge characterizing the menopause experience in those with HIV. The primary goal of this study was to assess inflammatory cytokine associations with symptoms and sex-specific differences, and the secondary focus was to assess differences among women by menopause status. Materials and Methods: One hundred persons living with HIV (PLWH) (25 men and 75 women recruited by menopause stage) completed a blood draw for hormones and cytokines and study questions on demographics, height and weight, reproductive health status, HIV symptoms, PROMIS-29 measures, and most recent viral load; study visits were synchronized to the early follicular phase in women with regular cycles. Results: In both sexes, the most burdensome HIV symptoms were muscle aches/joint pain, difficulty falling asleep, fatigue, and neuropathy. Three of the five symptoms where burden scores differed by menopause stage were related to pain with highest scores in the premenopause group; the postmenopause group also demonstrated a similar burden for muscle aches/joint pain while scores for men and perimenopause women were lowest. Pain intensity scores on the PROMIS-29 also varied significantly by groups. After controlling for sex, menopause stage and body mass index, significant differences were noted in C-reactive protein (CRP), interleukin (IL)-6, and IL-8 for PLWH who reported muscle aches/joint pain. Conclusions: Our findings suggest enhanced burden for HIV-related symptoms in women in the early follicular phase, possibly owing to menstruation. This supports the need for more targeted investigations in younger cycling women with HIV at multiple phases across the menstrual cycle. Muscle aches/pain are strongly associated with decreased CRP and IL-8 levels and increased IL-6 levels suggesting the need for further investigation of the biological pathways contributing to pain in PLWH. Finally, there is evidence to support that in PLWH, systemic inflammation is heightened above recommended clinical guidelines even when viral load is undetectable supporting the need for further study of the effects of persistent elevated inflammation on health outcomes.