Comorbidities in Women Living With HIV

A Systematic Review

Sonia Raffe; Caroline Sabin; Yvonne Gilleece


HIV Medicine. 2022;23(4):331-361. 

In This Article

Abstract and Introduction


Objectives: Effective antiretroviral therapy (ART) has improved the life expectancy of women living with HIV (WLWH). This population is now experiencing age-related comorbidities. This systematic review presents the current understanding of the prevalence and impact of comorbidities in WLWH in the modern ART era.

Methods: MEDLINE and Embase were searched for studies (1 January 2010 to 1 September 2020) reporting the prevalence of cardiovascular, bone, renal and neurocognitive disease in WLWH aged > 18 years. Studies were included if at least 100 participants (or > 50%) were female and data analysis included prevalence by sex.

Results: In all, 3050 articles were identified and screened; 153 full-text articles were assessed for eligibility and 38 were included in the final review. Significant gaps in the literature were identified, notably a lack of data on WLWH aged > 50 years. The data suggest a high burden of cardiovascular, bone, renal and neurocognitive disease in WLWH compared with HIV negative women. Traditional risk factors, such as hypertension, diabetes and dyslipidaemia, were common and often poorly managed. Generalizability of the results was limited, as many studies were conducted in the USA. Comparisons between WLWH and men with HIV were limited by marked differences in demographic and socioeconomic factors.

Conclusions: Women living with HIV experience a high burden of comorbid disease. Traditional risk factors are common and often poorly managed. This review also highlights the magnitude of differences between women and men living with HIV beyond the pathophysiological. Future research must unpick the complex drivers of morbidity in WLWH, to improve the holistic management of this population.


Over half of all people living with HIV (PLWH) globally are female.[1] While this proportion is lower in many resource-rich settings, 35.3% of new HIV diagnoses in Europe in 2018 were in women.[2] Despite this, our understanding of HIV in women is limited, with both publicly funded and industry-sponsored HIV trials often failing to demonstrate adequate female representation.[3]

Effective combination antiretroviral therapy (ART) has markedly improved the life expectancy of PLWH.[4] Consequently, PLWH are experiencing an increasing burden of age-related comorbid disease[5] with likely contributions from immune activation, exhaustion, senescence and chronic inflammation.[6] The ageing process is complex, and numerous clinical and lifestyle factors add to the challenge of apportioning causation.

Ageing and multimorbidity in PLWH create a unique set of challenges for those providing HIV-related care. Additional expertise in the screening and management of a greater number of conditions is required. Careful consideration of ART selection is needed to avoid compounding comorbidity risk and drug–drug interactions that could jeopardize the successful management of both HIV and the comorbid condition. It is essential that care providers understand, and are prepared for, the changing needs of PLWH.

Evidence suggests that the experience of women ageing with HIV differs from that of men. An analysis of the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort found that women living with HIV (WLWH) experienced greater multimorbidity at a younger age than their male counterparts and that every individual comorbidity, except for non-AIDS malignancies, carried an excess mortality risk.[7] Marked disparities are projected among key populations of PLWH in the US, with the highest burden of multimorbidity predicted among black women who inject drugs and the greatest increase in multimorbidity among Hispanic heterosexual women.

A notable physiological difference between men and women which may contribute to differing health outcomes, is the difference between sex hormones, reproductive capability and transition through the menopause. The oestrogen-deficient postmenopausal state is a well-recognized driver of cardiovascular disease (CVD), metabolic syndrome, bone density loss and decline in cognitive function in the general population,[8–11] although little is known about the impact of reproductive ageing on the development of age-related comorbidities in WLWH.[12] In addition, greater systemic immune activation,[13] sex-specific differences in immune response to HIV infection[14] and differing pharmacokinetic profiles may further explain the different outcomes between women and men with HIV.[15] There are also marked demographic and socioeconomic differences between women and men with HIV which may impact on the success of health promotion and disease prevention activities, and on the ability to access and engage with health services.

To address this evidence gap, this systematic review presents a summary of our current understanding of the prevalence and impact of cardiovascular, bone, renal and neurocognitive disease in WLWH, in resource-rich settings, in the modern ART era.