- Researchers compared the health of HIV-positive and HIV-negative women
- Women with HIV were nearly 60% more likely to have another health condition
- HIV-positive women developed two comorbidities 30 years earlier on average
Like everyone else, HIV-positive people develop other health conditions as they age. Such conditions can include thinning bones, type 2 diabetes and higher-than-normal blood pressure. These other conditions are called comorbidities. Research suggests that some HIV-positive people may develop more comorbidities and/or develop them earlier than their HIV-negative counterparts. Much of the research on comorbidities and HIV has been done with males. Now a team of scientists in Vancouver, in a study called CARMA, has begun to study the issue of comorbidities in women with and without HIV infection.
In a report to be published in the journal AIDS, the scientists found that HIV-positive women (who were on average younger than their HIV-negative counterparts) were more likely to have more comorbidities, particularly mental health issues. HIV-positive women were also more likely to smoke tobacco. The scientists encouraged healthcare providers caring for HIV-positive women to focus on smoking cessation and to screen for and provide “appropriate management of mood and anxiety disorders.”
Vancouver scientists collected health-related information from 267 HIV-positive and 276 HIV-negative women enrolled in a study called Children and Women: Antiretrovirals and Markers of Aging (CARMA). The HIV-positive women were recruited when they visited the Oak Tree Clinic. According to the scientists, the clinic provides “specialized HIV care to women, children and families living with or affected by HIV in B.C.” The HIV-negative women were recruited from advertisements. The data were collected between December 2008 and October 2017. The present analysis relies on the initial data collected.
In general, both groups of women were similar, though HIV-positive women were, on average, a few years younger. Major differences between the two groups of women were as follows:
- HIV positive – 48%
- HIV negative – 32%
- HIV positive – 41%
- HIV negative – 70%
In general, HIV-positive women were nearly 60% more likely to have a comorbidity than HIV-negative women. Here are some factors that affected the distribution of comorbidities:
As they aged, HIV-positive women seemed to accumulate comorbidities faster than HIV-negative women.
According to the scientists, “Overall, women with income greater than CAN $15,000/year had, on average, 18% lower rate of multiple diagnoses [of comorbidities] than those with lower incomes.” This relationship occurred regardless of their HIV status.
The scientists also stated that, overall, “…tobacco smoking was significantly associated with the number of [comorbidities diagnosed]” even after taking into account income, HIV status or other factors. Specifically, current smokers had a 45% higher rate of comorbidities and past smokers had a 38% higher rate of comorbidities than women who had never smoked.
Types of comorbidities
The scientists found that HIV-positive women were more likely to have the following diagnoses:
A cluster of mental health conditions—depression, anxiety and panic disorder
- HIV positive – 42%
- HIV negative – 27%
Hepatitis C virus
- HIV positive – 40%
- HIV negative – 18%
Thinner-than-normal bones (including osteoporosis and osteopenia)
- HIV positive – 21%
- HIV negative – 3%
Number of medicines
Overall, a trend emerged whereby the older an HIV-positive woman, the more likely that she was taking more medicines than an HIV-negative woman of similar age. This difference was probably driven by older HIV-positive women having more comorbidities.
Two other relationships to the number of medicines taken, regardless of HIV status, were as follows:
The scientists stated that women whose income was $15,000/year or greater “used 28% fewer medications than those with incomes less than $15,000/year.”
The scientists stated that “current smokers were using 85% more medications, and past smokers were using 55% more medications than participants who had never smoked.”
HIV-positive women were more likely to use supplements than HIV-negative women. Regardless of HIV status, current smokers were 52% less likely to use supplements.
Overall, similar proportions of women (about 50%) received treatment for comorbidities. However, the scientists found that fewer HIV-positive women were taking treatment for a comorbidity than their HIV-negative counterparts, as the following examples show:
- HIV positive – 67%
- HIV negative – 100%
- HIV positive – 34%
- HIV negative – 59%
- HIV positive – 45%
- HIV negative – 80%
- HIV positive – 23%
- HIV negative – 47%
Chronic obstructive pulmonary disease
- HIV positive – 27%
- HIV negative – 50%
CARMA was not designed to provide an in-depth report on prescriptions for or adherence to treatment for comorbidities. The researchers are therefore not sure why some HIV-positive women were not taking medicines for the conditions reported above.
The scientists found cases among the HIV-positive women where drug interactions could have potentially occurred. It is likely that these women could have benefitted from a consultation with a pharmacist.
Bear in mind
After taking into account socio-demographic factors, the scientists found that HIV-positive women compared to HIV-negative women “have an increased number of [comorbidity] diagnoses, and this difference becomes larger with age.”
According to their data, the scientists stated that they found a concerning trend: HIV-positive women “would develop, on average, two comorbidities 30 years earlier than their HIV-negative peers.” The Vancouver scientists are not sure why this apparent acceleration of aging occurs. However, other scientists who study the effect that HIV has on the immune system suggest that one or more of the following factors may play a role in the ongoing immunological dysfunction and accelerated aging of the immune system seen in chronic HIV infection:
- continuous activation and inflammation of the immune system, which is only partially diminished with treatment
- co-infection with CMV (cytomegalovirus infection), a member of the herpes virus family
- some unfriendly bacteria that live in the intestine and are directly able to enter the bloodstream through (or transmit their proteins across) the intestinal wall. These unfriendly germs and/or their proteins may adversely affect the immune system and other organ-systems over the long term.
Note that the present study is observational in nature with data captured only at one point in time. Such snapshot studies are good at finding associations but cannot prove cause and effect. Specifically, the present study, though well designed, cannot prove that HIV-positive women outside of this study will develop problems at the same rate as women inside the study. If the scientists could secure long-term funding, they would be able to capture data at multiple points in time from the same person. Then CARMA would be able to make more accurate predictions about the future risk of comorbidities in HIV-positive women.
Other studies of HIV-positive people have also found high rates of smoking and mental health conditions. These other studies support the overall findings from CARMA.
What to do?
The CARMA scientists encourage healthcare providers to screen HIV-positive women for tobacco use and to offer support to those who smoke on the journey to quitting. These interventions are important because the CARMA scientists found a strong statistical relationship between tobacco use and poor health. Separate research by the CARMA team suggests that smoking also contributes to the aging process in HIV-positive women.
The relatively high rate of a cluster of mental health conditions found in HIV-positive women is something that requires more attention. Poor mental health can degrade quality of life and lead to worse health. The CARMA scientists encouraged healthcare providers to screen HIV-positive women for mental health conditions and provide “appropriate management of mood and anxiety disorders, particularly in a population of aging individuals with increased morbidity.”
About 40% of HIV-positive women in the study had been exposed to hepatitis C virus (HCV) at some point in their lives. The CARMA scientists were not able to check if the women were currently infected with HCV. However, screening for current HCV infection in HIV-positive women may be useful. In cases where the infection is found to be active, an offer of treatment would be a step forward to curing HCV co-infection. Some of the women may also need to be referred to harm reduction services.
The results in this analysis of CARMA point to the importance of income as a factor on health. In the future, the effect of income supplementation (and/or other forms of socio-economic support such as housing and access to healthy food) on the long-term health of HIV-positive women is an area that could be explored.
For the future
The CARMA study is an exciting platform for conducting research with HIV-positive women. If the CARMA team were to receive additional funding, more much-needed research in this population could be conducted over the long-term.
—Sean R. Hosein
- Donaldson MA, Campbell AR, Albert AY, et al. Comorbidity and polypharmacy among women living with HIV in British Columbia. AIDS. 2019; in press.
- Ziada AS, Lu MY, Ignas-Menzies J, et al. Mitochondrial DNA somatic mutation burden and heteroplasmy are associated with chronological age, smoking, and HIV infection. Aging Cell. 2019; in press.
- Arshad O, Gadawska I, Sattha B, et al. Elevated cell-free mitochondrial DNA in filtered plasma is associated with HIV infection and inflammation. JAIDS. 2018 May 1;78(1):111-118.
- Thompson CG, Rosen EP, Prince HMA, et al. Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species. Science Translational Medicine. 2019 Jul 3;11(499).
- Costiniuk CT, Salahuddin S, Farnos O, et al. HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long-term suppressive antiretroviral therapy. AIDS. 2018 Oct 23;32(16):2279-2289.
- Bernal E, Martinez M, Torres A, et al. T cell senescence predicts subclinical atherosclerosis in HIV-infected patients similarly to traditional cardiovascular risk factors. Antiviral Research. 2019 Feb;162:163-170.
- Duffau P, Ozanne A, Bonnet F, et al. Multimorbidity, age-related comorbidities and mortality: association of activation, senescence and inflammation markers in HIV adults. AIDS. 2018 Jul 31;32(12):1651-1660.
- Heath JJ, Fudge NJ, Gallant ME, et al. Proximity of cytomegalovirus-specific CD8+ T cells to replicative senescence in human Immunodeficiency virus-infected individuals. Frontiers in Immunology. 2018 Feb 15;9:201.
- Ballegaard V, Brændstrup P, Pedersen KK, et al. Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV. Scientific Reports. 2018 Feb 28;8(1):3778.
- Pallikkuth S, De Armas LR, Pahwa R, et al. Impact of aging and HIV infection on serologic response to seasonal influenza vaccination. AIDS. 2018 Jun 1;32(9):1085-1094.
- Desai SN, Landay AL. HIV and aging: role of the microbiome. Current Opinion in HIV/AIDS. 2018 Jan;13(1):22-27.
- Tanaskovic S, Price P, French MA, et al. Impaired upregulation of the costimulatory molecules, CD27 and CD28, on CD4+ T cells from HIV patients receiving ART is associated with poor proliferative responses. AIDS Research and Human Retroviruses. 2017 Feb;33(2):101-109.
- Cobos Jiménez V, Wit FW, et al. T-cell activation independently associates with immune senescence in HIV-infected recipients of long-term antiretroviral treatment. Journal of Infectious Diseases. 2016 Jul 15;214(2):216-25.
- Eberhard JM, Ahmad F, Hong HS, et al. Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment. Clinical and Experimental Immunology. 2016 Nov;186(2):227-238.
- Appay V, Sauce D. Assessing immune aging in HIV-infected patients. Virulence. 2017 Jul 4;8(5):529-538.
- Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature Medicine. 2006 Dec;12(12):1365-71.
- Ramendra R, Isnard S, Mehraj V, et al. Circulating LPS and (1→3)-β-D-Glucan: A folie à deux contributing to HIV-associated immune activation. Frontiers in Immunology. 2019 Mar 18;10:465.
- Mehraj V, Ramendra R, Isnard S, et al. Circulating (1→3)-β-D-Glucan is associated with immune activation during HIV infection. Clinical Infectious Diseases. 2019; in press.
- Hoenigl M. Fungal Translocation: A driving force behind the occurrence of non-AIDS events? Clinical Infectious Diseases. 2019; in press.
- Wang Z, Gurule EE, Brennan TP, et al. Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane. Proceedings of the National Academy of Sciences USA. 2018 Mar 13;115(11):E2575-E2584.