ESCMID Online Lecture Library. by author

Improving Patient Safety: the Neglected Impact of Age and Gender, ESCMID Postgraduate Technical Workshop HIV in men, women and elderly Juan Ambrosioni MD, PhD

Content HIV in men and women: differences and similarities -Transmission, prevention, treatment -Timing of HIV diagnosis: Early vs. Late presentation -Not all men are equal for HIV: MSM vs. Heterosexuals -Specific vulnerable women populations (elderly, adolescents) HIV and age -HIV-positive patients, an aging population: reasons -Effect of HIV on aging (immunity, metabolic, neoplastic) -Effect of aging on HIV Conclusions and take-home messages

HIV in men and women: are available data applicable to women? HIV cure studies, but it happens with all studies Johnston et al. AIDS Res Hum Retrov. 2015

-Transmission, prevention, treatment For a given sexual intercourse, always higher risk of transmission for the receptive partner (anal > vaginal > oral, always higher if ejaculation) -A man can be insertive or receptive, but a woman is always receptive -However, in many settings (e.g. BCN) epidemics is driven by MSM (PHI) Varghese B, et al. Sex Transm Dis. 2002

-Transmission, prevention, treatment Effective measures to decrease female-to-male transmission (circumcision, 3 large RCT in Africa), but not in the other side Microbicides, only modest results, difficult to apply (CAPRISA) In many settings, poor power of decision for women to impose the use of condoms Siegfried et al. Cochrane Syst Rev 2009 Abdool Karim et al. Science 2010

-Transmission, prevention, treatment Abdool Karim et al. Science 2010

-Transmission, prevention, treatment Particular situations SHOULD be considered for therapy in women: PREGNANCY Irrespective of the guideline: ALWAYS PRIORITY FOR TREATMENT. If possible, do not stop ART after delivery. MTCT is less than 1% for women effectively on ART WHO consolidated guidelines 2013

WHO consolidated guidelines 2013 -Transmission, prevention, treatment B+: Lifelong B: al least pregnancy and breastfeeding

-Transmission, prevention, treatment Particular situations SHOULD be considered for therapy in women: D-D interactions, pregnancy desire, comorbidities and toxicities (e.g. osteoporosis) Optimal ARV regimen for women? EFV? Yes or no? It won t be longer contraindicated in next EACS guidelines. Several PI and NNRTI may decrease contraceptive plasmatic levels, thus reducing efficacy Greig et al. Curr Opin Infect Dis, 2014 EACS Guidelines, 2015 (in preparation)

Drug choice for women Although few women in RCT. Higher % of discont. in RCT. More nausea and larger increases in weight with PI. NVP-EFV toxicity. Particularly pregnancy and contraception. Greig et al. Curr Opin Infect Dis, 2014

Antinori et al. HIV Medicine 2011, Breskin et al. Sex Transm Dis. 2015 Timing of HIV diagnosis: Early vs. Late presentation and co-infections Consistently, MSM population is diagnosed at earlier stages compared to heterosexual men and women Late presenters are much more frequent among populations with low perception of risk Several definitions. Largely accepted ( European ): -Late presenters: <350 CD4 cells (+/- opport. event) -Advanced disease: <200 CD4 cells (+/- opport. event) Some infections are rarely transmitted through heterosexual contacts, but frequently among MSM (HCV)

Specific vulnerable women populations (elderly, adolescents) Extreme age groups are at particular risk for acquiring the infection and to neglect the possibilities of being infected Adolescents: in countries with the highest rates of HIV, males dominate sexual decision making. Older women: early menopause, neurocognitive impairment, osteoporosis. Frequently missed by the risk reduction programs Hardee et al. JAIDS 2014 Durvasula. Behav Med 2014

Content HIV in men and women: differences and similarities -Transmission, prevention, treatment -Timing of HIV diagnosis: Early vs. Late presentation -Not all men are equal for HIV: HSH vs. Heterosexuals -Specific vulnerable women populations (elderly, adolescents) HIV and age -HIV-positive patients, an aging population: reasons -Effect of HIV on aging (immunity, metabolic, neoplastic) -Effect of aging on HIV Conclusions and take-home messages

-Not all men are equal for HIV: MSM vs. Heterosexuals Intergenerational sex as a risk factor for HIV in MSM Anema et al. Curr HIV/AIDS Rep, 2013

-HIV-positive patients, an aging population: reasons Inelmen et al. Agin Clin Exp Res, 2014

-HIV-positive patients, an aging population. Approach for care providers. Inelmen et al. Agin Clin Exp Res, 2014

Deeks SG et al. Curr Opin Immunol, 2012 Tsoukas, Curr Opin HIV AIDS, 2014 Senescence and immune senescence Normal cell process, common pathway of many cell lines, characterized by shortened telomeres Immune senescence is associated with a lost of expression of CD28 and increase expression of CD57 Senescent immune cells are: highly differentiated, very limited capacity of proliferation and produce a pro-inflammatory cytokine profile

Senescence and immune senescence Biologically (organism): -increased susceptibility to infection -lost of protection from previous vaccinations -decreased responsiveness to new vaccinations -decreased surveillance against cancer -increased auto-inmmunity - frailty High proportion of CD28- cells and increased chronic inflammation in HIV-infected individuals This immune senescence may be, at least in part, responsible for the non-aids co morbidities Deeks SG et al. Curr Opin Immunol, 2012 Brothers et al. J Infect Dis, 2014

GALT depletion during PHI Undetectable not equal to no virus Deeks SG et al. Curr Opin Immunol 2012 Deeks SG BMJ 2009

-The window-of-opportunity is not very long -Depletion of GALT occurs really early during PHI GALT depletion Fiebig et al, AIDS 2003. McMichael et al, Nat Rev Immun 2010.

HIV-related cognitive disorders, ilicit drugs, ARV (EFV) Smoking, dyslipidemia, ARV (ABC?) Remember: not HIV alone ARV (TDF), malnutrition Hepatotoxic drugs HBV, HCV co-infection, alcohol

Addition of biological, epidemiological and sociological aspects What lacks? The direct association of risk phenotype and HIV/AIDS progression. Tsoukas, Curr Opin HIV AIDS, 2014

On the other side Impaired immunological response to ART in older individuals Linear regression model. Study performed in African adults (N=9800), median age=37, female 60%. Linear regression model. Study performed in African adults (N=8800), median age=35, female 65%. Semeere AS et al, JAIDS 2014. Mutevedzi PC et al. Plos One 2011.

Conclusions and take-home messages Important disparities when considering men and women infected with HIV, or at risk for acquiring HIV Women are more vulnerable (particularly very young and older women) and have more risk of transmission MTCT remains an issue in limited resources settings Late presentation is more frequent for heterosexuals than MSM, but MSM drive epidemics in many places HIV infection is itself an accelerating aging process (more metabolic, neurocognitive and neoplastic risk) driven by chronic inflammation in the context of other contributing factors

What can we do? Disparities among men and women Remember specific needs for women, particularly very young and older women (stigma, vulnerability, pregnancy, drug interactions, contraceptives) Test for HIV EVERY SINGLE PREGNANT WOMEN. TREAT ALL THEM!!! Think the possibility of HIV infection in heterosexual men and women, to avoid late presentation. It s better get upset a patient than losing the diagnosis

What can we do? Reduce the impact of accelerated aging Consider previous co-morbidities and avoid toxicity potentiation If possible, treat HIV infection in the earliest possible stage Always discuss and work with the patient the classic risk factors for cancer, CV, brain, bone and kidney disease Think about co-infections and repeat serologies when appropriate (Ex. HCV for MSM) Always consider ART changes, simplifications or improvements

Questions and discussion Questions, comments, anything? Thank you very much for your attention!