US study suggests women living with HIV should be screened earlier for non-AIDS co-morbidities

Women living with HIV are at greater risk of developing non-AIDS co-morbidities than their HIV-negative peers, with the difference most evident among younger women, according to US research published in Clinical Infectious Diseases. Overall, women living with HIV were 36% more likely to develop non-AIDS co-morbidities during the study period compared to women without HIV, after adjusting for demographics factors, drug and alcohol use, body mass index (BMI) and income level. This rose to 48% among women aged below 25 – a group not traditionally prioritised in co-morbidity screening guidelines.

“These findings substantiate that women living with HIV are susceptible to premature multimorbidity… and that co-morbidity risk assessment and intervention should optimally begin for women in their childbearing years,” the authors write.

A number of studies suggest that people living with HIV are more likely to develop co-morbidities that are not related to AIDS, such as heart disease or high blood pressure, at a younger age than people who are not living with HIV. There is also some evidence indicating that women living with HIV are at greater risk than men. However, women living with HIV are generally underrepresented in research and incidence of co-morbidities among this group is not well understood.

With this in mind, a team of researchers led by Dr Lauren Collins of the Emory University School of Medicine undertook a study to determine the prevalence, incidence and associated risk factors of ten co-morbidities among women living with or at risk of HIV. The co-morbidities evaluated in the study were high blood pressure, high cholesterol, heart disease, diabetes, chronic kidney disease, liver, bone, and lung disease, psychiatric illness, and non-AIDS-related cancer.

They used data from over 3000 participants in the Women’s Interagency HIV Study, the largest prospective US-based cohort of women living with HIV and HIV-negative women at risk of acquiring HIV. Women without HIV are recruited based on HIV risk-factors such as substance use and a history of STIs.

There were 2239 women living with HIV and 890 HIV-negative women included in the analysis, with 36,589 person-years of follow-up in total. Participants were restricted to those on whom there were data between 2009 and 2018.

The median age of participants was 37 years and 65% were Black. Only 35% of women in the study had greater than high school education and all of the participants had an annual household income below $24,000, with 56% earning below $12,000. Both women living with and without HIV had a median score of 12 on a scale of 0-60 for depressive symptoms, with the threshold for depression being 16 or above.

Along with these similarities, there were also several significant differences between the two groups. HIV-negative women were significantly more likely to smoke (54% vs 44%), drink alcohol (57% vs 47%), use crack/cocaine (15% vs 10%), and have a BMI of 30 kg/m² or above (47% vs 40%). Women living with HIV were more likely to use medication for high blood pressure (20% vs 16%), be living with hepatitis C (12% vs 9%) and hepatitis B (2% vs 1%), and to have worse kidney function.

At baseline, women living with HIV had a median CD4 count of 484 cells/mm³, over two-thirds (69%) were on antiretroviral treatment and just under half (45%) were virally suppressed. By the end of the study, the proportion of women virally suppressed had risen to over 80%.

When enrolling in the study, women living with HIV had, on average, 1.4 of the ten co-morbidities evaluated compared to 1.2 among HIV-negative women. They were more likely to have liver disease (26% vs 16%) and psychiatric illness (26% vs 21%), but otherwise there was no significant difference between the groups in terms of prevalent disease.

During the study period, women living with HIV were 36% more likely to develop co-morbidities during the study period compared to women without HIV (aIRR 1.36; 95% CI 1.02-1.81, p < 0.0001) after adjusting for BMI, current use of drugs and alcohol, and socio-demographic factors such as age, race and income.

"Socio-economic and lifestyle risk factors were significantly associated with co-morbidities, whereas HIV-specific risk factors (such as low CD4 count or high viral load) were not."

High blood pressure was the most common co-morbidity among women living with HIV with 55% developing it over the course of the study. However, this was similar to HIV-negative women, of whom 53% developed high blood pressure.

Women living with HIV were more likely to develop chronic kidney disease (13% vs 5%), liver disease (25% vs 12%), psychiatric illness (42% vs 35%), high cholesterol (35% vs 29%) and bone disease (38% vs 29%) during the study. There was no significant difference in incidence between women with or without HIV of the other five co-morbidities studied.

Surprisingly, when analysed by age group, the authors found that the difference in incidence risk was greatest among very young women. Women living with HIV aged below 25 were 48% more likely to develop a co-morbidity compared to their HIV-negative peers. This compares, for example, to a 36% increase in risk among women aged over 55. The co-morbidities with the highest incidence rates among women living with HIV aged below 25 were psychiatric illness, high blood pressure and lung disease.

The study investigated a range of risk factors that might explain the elevated risk of co-morbidities among women living with HIV. They found that socio-economic and lifestyle risk factors such as low income, high BMI, smoking and drug use were significantly associated with higher incidence, whereas HIV-specific risk factors (such as low CD4 count or high viral load) were not.

The authors speculate that the early occurrence of co-morbidities among women living with HIV is multi-factorial. In addition to the socio-economic and lifestyle risk factors identified above, they highlight the higher prevalence of viral co-infections compared to the general population, long-term exposure to certain types of antiretroviral drugs, lower oestrogen levels among menopausal women (which may occur earlier amongst women living with HIV), and HIV-associated chronic inflammation, as possible contributors to co-morbidity risk. The reason for younger women living with HIV having greater risk of developing co-morbidities remains unclear, and the authors hope to investigate this further.

They argue that age-based general population screening guidelines are inappropriate for people living with HIV, and especially for women living with HIV. They call for earlier screening, sex-stratified guidelines and risk assessment tools that take both HIV status and sex into account. Given the major contribution of social determinants of health (such as poverty and ethnic inequality) to the development of co-morbidities among women, regardless of HIV status, the authors also emphasise the importance of addressing these systemic issues.

“Innovative HIV- and female-specific clinical risk-assessment and risk-reducing tools… will be paramount to address the synergy of HIV and premature multimorbidity, fueled by underlying social determinants, in this high-risk population”, they conclude.