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HIV Infection in Women Judith S. Currier, MD University of California, Los Angeles

HIV Infection in Women Judith S. Currier, MD University of California, Los Angeles. Overview. Epidemiology Natural History Treatment Issues. Case 1. 42 year old woman presents to ER with seizure No past medical history Born in Los Angeles, no travel

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HIV Infection in Women Judith S. Currier, MD University of California, Los Angeles

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  1. HIV Infection in Women Judith S. Currier, MD University of California, Los Angeles

  2. Overview • Epidemiology • Natural History • Treatment Issues

  3. Case 1 • 42 year old woman presents to ER with seizure • No past medical history • Born in Los Angeles, no travel • Works in Medical Records at local hospital • Married, monogamous for 15 years, no children • Physical exam within normal limits • Labs WBC 2.7, hgb 9.8 plt 320

  4. DDx includes brain abscess or malignancy • HIV testing discussed with patient

  5. HIV Testing Recommended • She reluctantly reports that her husband is HIV + • He has been on treatment for past five years • She has never been tested • She has been in good health without symptoms ( recurrent leukopenia noted in outpatient records) • Her husband suggested that there was nothing to do if she did not have any symptoms…. And she believed him

  6. Follow-up • HIV test positive, • CD4 =25 cells/mm3 • Toxo IgG positive, Ig M negative • Starts on pyrimethamine/sulfadiazine and folinic acid • Steroids tapered • Started on antiretroviral therapy and responds well Why did this woman resist HIV testing for 10 years?

  7. Impact ongoing access to diagnosis and quality care Stigma/fear of disclosure Disempowerment Caregivers for others Domestic violence Lack of health insurance Co-morbidities Cultural barriers Poverty

  8. Epidemiology Global US

  9. Global summary of the AIDS epidemic  2011 34.2 million [31.8 million–35.9 million] 30.7 million [28.6 million–32.2 million] 16.7 million [15.7 million–17.8 million] 3.4 million [3.1 million–3.9 million] 2.5 million [2.2 million–2.8 million]2.2 million [2.0 million–2.4 million] 330 000 [280 000–380 000] 1.7 million [1.6 million–1.9 million]1.5 million [1.3 million–1.7 million] 230 000 [200 000–270 000] Total Adults Women Children (<15 years) Total Adults Children (<15 years) Total Adults Children (<15 years) Number of people living with HIV People newly infected with HIV in 2011 AIDS deaths in 2011

  10. Different Groups of Women Have Their Own Needs and Issues Female adolescence WOMEN Pregnancy Older Women

  11. Each Year, American Youth Experience • Nearly 900,000 teen pregnancies • Approximately 9 million new cases of STDs • An estimated 15,000 new cases of HIV among those aged 15-24 U.S. Teenage Pregnancy Statistics, Alan Guttmacher Institute, 2004, and Weinstock, H., et al., Sexually Transmitted Diseases in American Youth 2000

  12. Vulnerability of Female Youth to HIV • Sexually active female teenagers may be biologically more susceptible to HIV acquisition than older women • Highest age-specific rates of both gonorrhea and Chlamydia may increase the relative risk of acquiring HIV 2-3 fold • The less mature cervix commonly has larger areas of cervical ectopy than that of a more mature woman. • Age-discrepant sexual relationships Hopkins report

  13. Unique Issues of Adolescents Not still children – not yet adults • Increasingly earlier onset and physical changes of puberty • Age at menarche: 16.9 years in 1800 vs. 12.8 in 2000 • Cognitive development – transition to abstract reasoning • Continuing development of gender identity • Biological/social factors make adolescents vulnerable to unsafe sexual practices

  14. Older Women 69 yr old Hispanic woman undergoing colposcopy Resident performing procedure sustains a needlestick Requests HIV testing on the patient The patient tests positive Her husband died of TB seven years earlier She had never been offered HIV testing and was not aware of his HIV CD4 was 92 cells/mm3 Viral load 45,000

  15. How Many Women Age 65-74 Years Report Having Sexual Intercourse in Prior Year ? A. 10% B. 25% C. 40% D. 70% • My grandmother has sex?

  16. Sex is Not Only for the Young Percentage reporting sex in last 12 months Age Lindau NEJM 2007 357(8):762-774 National Social Life, Health, and Aging Project (NSHAP), 2004

  17. Sex is Not Only for the Young Percentage reporting sex in last 12 months Age Lindau NEJM 2007 357(8):762-774 National Social Life, Health, and Aging Project (NSHAP), 2004

  18. Estimated numbers of persons newly diagnosed with HIV/AIDS, by year and selected characteristics, 2009 – 40 states and 5 U.S. dependent areas with confidential name-based HIV infection reporting N = 42,959 Median: age 40-44 years 16.7 % aged > 50 years Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2009. Vol. 21. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2011: http://www.cdc.gov/hiv/topics/surveillance/resources/reports/., Table 1a

  19. Why are older patients getting infected? 1) Individual lack of awareness of HIV risk factors • Many older people are newly single • Poor understanding of their risk for a disease • Perceive as disease affecting young or gay people • Perceived risk decreased even among high risk groups • Levy et al. JAIDS 2003 33(Supp 2): S59-67. • Savasta et al., J Assoc Nurses AIDS Care 2005 15(1): 50-59.

  20. Why are older patients getting infected? 2) Altered biological risk for HIV acquisition • Women: changes related to menopause • No risk for pregnancy  risk compensation - Decreased need for condoms as birth control • Cervicovaginal changes favoring infection • ↓ estrogen → thinner epithelium, less mucous • risk of microabrasions • Immune system changes • ↑ CCR5+CD4+ T-cells (target for wild type virus) • ↑ pro inflammatory factors (↑ HIV replication) • Meditz et al., 2011 Conference on Retroviruses and Opportunistic infection, abstract #33 • Rollenhangen and Asin, Conference on Retroviruses and Opportunistic infection, abstract #776

  21. Why are older patients getting infected? Condom use is rare among persons age > 50 years National Survey of Sexual Health and Behavior (early 2009)  20% used a condom for any vaginal/anal sex Shick et al., J Sex Med 2010 7(suppl): 315-329.

  22. Why are older patients getting infected? • Inadequate efforts of care providers to assess and communicate risk • Infrequently assess risk (i.e., take a sex history) - Fear of angering or insulting - Shame or discomfort discussing sex with seniors (imagine Grandma and Grandpa doing it!) - Misinformed about sexual life of elders, perceive their patients as being at low risk • Poor skills at taking a sex history - Especially in persons > age 50 years Loeb et al., J Gen Intern Med 2011 7(suppl): 315-329.

  23. Older Women Immune reconstitution Co-morbid illnesses Poly-pharmacy Issues specific to older women Limited incomes Insufficient data on drug interactions in older pop Delay in testing Unprotected sex Nauen E. AIDS: A woman’s disease. 2002; Clark RA, Bessinger R. J Acquir Immune Defic Syndr Hum Retrovirol. 1997; Adler WH, et al. Mech Ageing Dev. 1987.

  24. Gender Differences in HIV Natural History

  25. Risk Factors for HIV Transmission Women are more susceptible than men to contract HIV through heterosexual intercourse Factors that increase the risk of transmission Presence of STD Role of contraception Stage of disease in partner Exposure site (oral, vaginal, anal) Substance use Social/behavioral Age DHHS. HRSA Care Action. HIV disease in women of color. 1999; NIAID. NIH. Fact Sheet. HIV infection in women. 2002; Fowler MG, et al. Obstet Gynecol Clin North Am. 1997; Lazzarin A, et al. Arch Intern Med. 1991.

  26. Viral Loads in Women Viral load lower in women Viral load higher in women Study N Moore (VI)* 1173 Sterling (1999) 71 Evans 42 Sterling (2001) 202 Moore (V)* Farzadegan 527 Anastos (IV)* 2859 Rezza 415 Lyles 149 Moroni 2011 Anastos (III)* Moore (IV)* Katenstein 391 Junghans (H)* 1337 Junghans (IDU)* Anastos (II)* Moore (III)* Bush 40 Anastos (I)* Moore (II)* Moore (I)* Kalish 494 750 675 600 525 450 375 300 225 150 75 0 CD4 count *Number represents total in study and not total in strata. Gandhi M, et al. 9th CROI, 2002. Abstract 775-W.

  27. Progression to new AIDS diagnoses or death same in both sexes 1Sterling. AIDS 2001; 2Junghans. AIDS 1999; 3Moore A. JAIDS 2002; 4Nicastri. AIDS 2005; 5Moore A. JAIDS 2003 [ Slide adapted from Monica Ghandi MD, UCSF)

  28. Rates of other clinical events same in both sexes in HAART era 1Lewden. JAIDS 2001; 2CASCADE. Lancet 2003; 3Gebo. JAIDS 2003; 4Floris-Moore. JAIDS 2003 Slide adapted from Monica Ghandi, MD UCSF

  29. Pharmacokinetics How Women Differ Drug interactions Lower body weight Hepatic metabolism Effects of pregnancy Higher body fat content Hormonal differences Hader SL, et al. JAMA. 2001; DHHS. Guidelines…, February 2002; Garcia PM, et al. ClinicalUpdate. 2000; Anderson GD. JGend Specif Med. 2002; Mirochnick M. Ann NY Acad Sci. 2000; Mildvan D, et al. J Acquir Immune Defic Syndr. 2002.

  30. Women and HIV: Lactic Acidosis • FDA received 60 reports of lactic acidosis associated with dual nucleosides; 55% mortality1 • 83% in women; 50% > 175 lbs • Mean time on ART= 255 days • 85% of 20 fatal cases were in women • Lactate levels measured in naïve pts treated with d4T containing HAART • 15/ 31 African women responding to tx had AE • 20% severe hyperlactatemia vs 0% among 31 men 1. Boxwell DE et al 39th ICAAC, Abst 1284 1999 2. Gerard, Poster 69 7th IWADRL, Dublin 2005

  31. Sex Differences in Toxicity- the NVP story • NVP FDA approved in 1996 adults based on benefit in treatment experienced patients • 2002 concern regarding toxicity in HIV negative HCW • Early studies of NVP conducted in early 1990s included few women • Reports of excess toxicity in women began to appear in literature 2001-2003 • 2004 Dear Doctor Letter and Black Box warning added to label- sex specific recommendation about use of nevirapine

  32. Women and NNRTI toxicity • 9.5% women developed rash vs 1.1% men in a prospective trial (Bersoff-Matcha Sj et al, CID 2001) • Women 5 times more likely than men to develop rash to NVP or EFV in retrospective review (Mazhude C et al, AIDS 2002) • 3 fold higher risk (5.8 vs 2.2%) of “symptomatic hepatitis” among women on NVP • Women with CD4+ cell counts >250 cells/mm3 11% risk vs. 0.9% for women with CD4 + cell counts <250cells/mm3 • Men with CD4+ cell counts >400 cells/mm3 6.3% risk vs 2.3% for men with CD4+ <400 cells/mm3

  33. 32 yr old woman dx HIV 11/05 when she was found to have an abnormal pap smear • Husband died of AIDS one month earlier • CD4 cell count 200, VL 46,000 • Started on efavirenz/zidovudine/lamivudine with good response • Six weeks later found to be pregnant • Therapy changed to nelfinavir/zidovudine/lamivudine • Referred to UCLA for management during pregnancy • 8 weeks on new regimen, VL still 18,000 copies She reports adherence to medication with minimal side effects

  34. U.S. Pregnancies: Unintended vs. Intended Unintended (49%) Intended (51%) Unintended Births (22.5%) Elective Abortions (26.5%) Finer et al, 2006 (2002 data)

  35. Time of HIV Diagnosis in Pregnant Women PACTG 367 n=1,527 pregnancies Timing of HIV Diagnosis

  36. “COMPETING” ISSUES:Use of ARV in Pregnancy SAFETY EFFICACY FOR MOTHER SAFETY FOR BABY REDUCE TRANSMISSION

  37. GOAL • Uncomplicated pregnancy • Healthy HIV uninfected baby • Healthy mother who has not compromised her future treatment options for the management of her disease

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