1. Women and HIV Lucille Sanzero Eller, PhD, RN Associate Professor Rutgers, The State University of New Jersey College of Nursing A Local Performance Site of the NY/NJ AETC June 2008

2. Objectives (1) 1. Discuss the epidemiology of HIV in women. 2. Describe gender-specific symptoms in HIV+ women. 3. Discuss ARV treatment considerations for HIV+ women.

3. Objectives (2) 4. Identify psychological factors in HIV+ women. 5. Discuss contraception and pregnancy in HIV+ women. 6. Describe assessment and counseling issues for women with HIV.

4. Epidemiology of HIV in Women (1) Proportion of AIDS cases in women steadily increased since HIV epidemic began – 1985 - 8% women – 2005 - 27% women Women of color disproportionately infected – Hispanic and African American women 25% of all U.S. women 80% of women with HIV in the U.S.

5. Epidemiology of HIV in Women (2) HIV infection in African American women in 2002: – leading cause of death for those aged 25 to 34 years – 3rd leading cause of death for those aged 35–44 years – 4th leading cause of death for African American women aged 45–54 years and for Hispanic women aged 35–44 years (CDC, May 2006)

6. Race/ethnicity of Women With HIV/AIDS Diagnosed 2005 (CDC, 2007) http://www.cdc.gov/hiv/topics/women/resources/factsheets/women.htm

7. Transmission categories and race/ethnicity of women living with HIV/AIDS 2005 (CDC, 2007)

8. HIV Transmission in Women  Most common routes of HIV infection for women  sex with an HIV-positive man  sharing injection drug works with someone with HIV  Male to female transmission is 1.9 times more effective than female to male transmission; women are about twice as likely as a man to contract HIV infection during unprotected vaginal intercourse

9. Viral load  Viral load in women  After adjustment for differences in measurement method, baseline CD4 + cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4 + counts >200 cells/mm 3  Despite lower viral loads, HIV disease progresses at the same rate in women as in men (Rezza et al., 2000)  Current clinical guidelines do not make a distinction by gender for the initiation of HAART

10. HIV-related Hormonal Changes (1)  HIV can affect the body's ability to produce and maintain hormone levels  Changes in the balance of estrogen, progesterone, or testosterone can lead to multiple symptoms (Margolese, 2004)

11. HIV-related Hormonal Changes (2)  Symptoms of hormonal imbalance:  Abnormal menstrual cycles, possibly including early menopause  Weight loss  Headaches  Mood swings  Depression

12. HIV-related Hormonal Changes (3)  Symptoms of hormonal imbalance:  Sleep disturbances  Fatigue  Decreased bone density  Vaginal dryness  Lack of sexual desire  Difficulty getting pregnant

13. HIV and Menstrual Problems (1)  Menstrual cycle changes  Increase in premenstrual symptoms  Changes may be due to  HIV itself  ARVs  other co-factors that may occur with HIV disease such as drug use

14. HIV and Menstrual Problems (2)  Hypermenorrhea- can predispose a woman to anemia, already a chronic problem in women with HIV  Amenorrhea- should be promptly evaluated to determine possible underlying causes  pregnancy  ovarian cyst  ovarian failure and premature menopause

15. HIV and Osteopenia  Study compared bone density in HIV+ (n=263) and HIV- (n=232) women aged 40 years and older (Arnsten et al., 2006)  prevalence of osteopenia, regardless of ART use, was  27% in HIV+ women  19% in HIV- women  Higher risk of osteopenia if  Black  Underweight  Used opiates

16. HIV and Menopause (1)  The “Ms Study” examined natural history of menopause in HIV-infected and drug using women (Schoenbaum, 2005)  571 women, 52.9% were HIV positive  median age was 43 years  53% had a history of illicit drug use  89% were women of color

17. HIV and Menopause (2)  Onset of menopause significantly differed  46 years [Interquartile Range (IQR) 39-49 years] for HIV+ women  47 years [IQR 39-48 years] for HIV- women  Those with CD4+ counts <200 cells/mm3 had earliest onset (median age 42.5 years)  No association between receipt of HAART and onset of menopause  Earlier onset of menopause combined with HIV disease contributes to risk of dyslipidemia and osteopenia

18. AIDS Complications in Women  AIDS complications unique to women  recurrent vaginal candidiasis  severe pelvic inflammatory disease  cervical dysplasia  cervical cancer  Women with HIV are at higher risk of developing cervical dysplasia, a precursor to cervical cancer  Risk is associated with immune deficiency (declining CD4 counts and higher HIV RNA levels  Risk is associated with human papillomavirus (HPV) which occurs in more than 60% of women with HIV (Abularach & Anderson, 2005)

19. HIV and Cervical Cancer  Cervical Cancer  Incidence is up to 9 times higher than the expected number of cases  Presents at more advanced stages  Metastasizes to unusual locations  Is less responsive to therapy

20. HIV and Oral Symptoms  Studies have shown a significant relationship between high viral load and both oral candidiasis and hairy leukoplakia (Greenspan et al, 2000; 2004; Patton et al., 2000)  Recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independent of CD4 count and HIV RNA level  HAART does not reduce the incidence of hairy leukoplakia or oral warts in women (Greenspan et al., 2004

21. HIV and Women: Studies (1)  The Women's Interagency HIV Study (WIHS)  established in 1993  investigated the impact of HIV infection on women  recruited 2066 HIV-positive and 575 HIV- negative women from six sites in the U.S.  The Women and Infants Transmission Studies (WITS)  multi-site observational study established in 1989  enrolled 2336 HIV-infected pregnant women and 1887 infants born to them

22. HIV and Women: Studies (2) NIH-funded clinical trials networks and pharmaceutical companies are trying to enroll more women into their clinical trials

23. HIV and Women: Studies (3)  10 primary care sites in the HIV Research Network (HIVRN) (N=19,500) (Gebo et al., 2005)  HIV+ women less likely than HIV+ men to receive prescriptions for the most effective treatments for HIV infection  Those less likely to receive clinically indicated ART :  <40 y.o.; women; African-Americans; IDUs; the uninsured or those with private insurance  Those more likely to receive clinically indicated ART :  older patients; men; Whites; Hispanics; those with risk factors other than IDU; those with Medicare coverage

24. HIV and Women: Treatment (1) Recommendations for treatment of women of reproductive age:  Indications for initiation of therapy and goals of treatment are same as for other adults and adolescents  Avoid Efavirenz for the woman who wants to become pregnant or who does not use effective and consistent contraception Panel on Clinical Practices for Treatment of HIV Infection, 2008

25. HIV and Women: Treatment (2) Recommendations for treatment of women of reproductive age:  For the woman who is pregnant, an additional goal of therapy is prevention of mother-to-child transmission, with a goal of viral suppression to <1,000 copies/mL  Selection of an ARV combination should consider known safety, efficacy, and pharmacokinetic data of each agent during pregnancy ( Panel on Clinical Practices for Treatment of HIV Infection, 2008)

26. Lipodystrophy Syndrome (1)  Metabolic and clinical features include:  insulin resistance  impaired glucose tolerance  type 2 diabetes  Hypertriglyceridemia  Hypercholesterolemia  increased free fatty acids (FFA)  decreased high density lipoprotein (HDL)  fat redistribution

27. Lipodystrophy Syndrome (2)  Higher incidence lipoatrophy with efavirenz + 2 NRTIs vs. lopinavir/ritonavir + 2 NRTIs (ACTG A5142)  thymidine analog use (D4T, ZDV) associates with lipoatrophy  Factors that increase risk of lipodystrophy syndrome  duration of treatment  age  degree of immune compromise

28. Lipodystrophy Syndrome (3) HIV+ women are nearly twice as likely as men to have symptoms of lipodystrophy  Women tend to experience fat accumulation in the abdomen and breasts  Men tend to experience fat depletion from the face and extremities

29. Contraception (1)  WIHS study- effects of hormonal contraceptives on HIV RNA and CD4 counts (Cejtin et al., 2003)  1721 women 50 y.o. or less, not menopausal  controlled for CD4 count, tobacco use, age, race, ART use, and a history of AIDS-defining illnesses  No effect on viral load; small increase in CD4 count, not clinically significant

30. Contraception (2)  WIHS study- effects of hormonal contraceptives on effectiveness of HAART (Chu et al., 2005)  77 hormonal contraceptive users matched with non-users on age, race, and pre-HAART CD4 count and viral load  Followed from point of HAART initiation  No effect on CD4+ cell count and viral load responses to HAART

31. Contraception (3)  Hormonal contraceptives can interact with ARVs and cause any of the following:  decreased contraceptive effectiveness  increased concentrations of the ARV  decreased concentrations of the ARV e.g. Fos-Amprenavir should not be co- administered with hormonal contraceptives  Amprenavir increases blood levels of both estrogen and progestin  oral contraceptives decrease Amprenavir levels

32. Contraception (4)  Copper IUDs  are associated with increased menstrual flow and duration  May contributing to HIV transmission risk  May contribute to anemia in HIV+ women

33. Stigma  Stigma of HIV disease has several negative consequences  secrecy and unwillingness to disclose serostatus  fear of being identified as HIV positive  isolation  reduced access to care  difficulties with medication adherence  unwillingness to seek social support (Carr & Gramling, 2004)

34. Social Support (1)  Social support includes the provision of  Emotional support  esteem  affiliation  Instrumental support  financial  housing  Informational support  advice  information

35. Social Support (2)  Women with HIV receive less social support than demographically similar women  Social support decreases as symptoms of HIV increase (Hough et al., 2003; Klein et al., 2000)  Social support reduces psychological distress and is a critical element in effective coping with HIV (Hough et al., 2005)

36. Social Support: INSPIRE Study (1)  Baseline data of INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study (Knowlton et al., 2006)  Examined role of social support in facilitating effective HAART use in 446 IDUs  34% female, 69% Black, 26% homeless, median age 43 years

37. Social Support: INSPIRE Study (2)  Adjusted odds of undetectable viral load (UVL) 3X higher in those with  high social support  stable housing  CD4 > 200  Adjusted odds of achieving UVL almost 60% higher (AOR = 1.57) in those reporting better patient-provider communication

38. Social Support: INSPIRE Study (3)  Interventions to facilitate effective HAART use in IDUs should promote  social support functioning  patient-provider communication  stable housing  drug abuse treatment (Knowlton et al., 2006)

39. Social Support  Study of social support in 147 poor, young (M=36 y.o., SD=7) urban, African American (87%) mothers with HIV (Hough et al. 2005)  47% of primary support network, who provided the most salient support were children  few friends, and almost no health care providers were reported as sources of social support

40. Social Support: Assessment  Scale to assess social support in HIV+ women and abused women is the Interpersonal Support Evaluation List (ISEL) (Cohen et al., 1985)  Scale available at http://www.psy.cmu.edu/~scohen/ISEL.html

41. Social Support: Study of Unsupportive Social Interactions (1)  Presence of friends, family, significant others is not necessarily supportive  Unsupportive social interactions may be detrimental  Study of relationship-specific unsupportive social interactions and depression in 146 HIV+ women (Scrimshaw, 2003)

42. Social Support: Study of Unsupportive Social Interactions (2)  28% asymptomatic, 29% symptomatic, 43% with AIDS  Mean age 35.6 years (SD D 5.6)  African American (33%), Puerto Rican (34%), White (33%)  Incomes: 36% < $10,000; 48% $10,000 and $19,999; 26% $20,000+  70% married or steady partner  73% mothers  55% IVDUs

43. Social Support: Study of Unsupportive Social Interactions (3)  Unsupportive social interactions from family  direct negative effect on depressive symptoms  Unsupportive interactions from a lover/ spouse and friends  interactive effect on depression  independently predicted high levels of depressive symptoms (Scrimshaw, 2003)

44. Social Support: Study of Unsupportive Social Interactions (4)  Number of HIV-related physical symptoms significantly associated with more unsupportive social interactions from all three sources:  family  lover/spouse  friends (Scrimshaw, 2003)

45. Assessment of Unsupportive Social Interactions (1)  Assess unsupportive illness-related social interactions during the past month Responses range from never (1) to all the time (5)  Ask whether others: 1. Were trying to be overly optimistic or cheerful 2. Were avoiding you or was uncomfortable being with you 3. Were unwilling to listen to you talk about the illness (Siegel et al., 1994; 1997)

46. Assessment of Unsupportive Social Interactions (2)  Ask whether others: 4. Resented the demands the illness placed on them 5. Said or did things that you found unhelpful or disturbing 6. Made you more dependent on assistance than you needed to be (Siegel et al., 1994; 1997)

47. Assessment of Unsupportive Social Interactions (3)  Questionnaire should be completed three times, once each for  lover/spouse  family  friends  Calculate 3 separate summary scores (i.e., the sum of the six items) to assess the frequency of unsupportive social interactions in each type of relationship ( Scrimshaw, 2003)

48. Depression (1)  Depression in women with HIV was 77% (Ickovics, 2001)  Depression in PLWHIV associated with:  poorer virologic response  increased likelihood of immunologic failure  incident AIDS defining illness  higher risk of all-cause, but not AIDS-related, death

49. Depression (2)  Depression following HAART initiation was associated with a greater likelihood of HAART discontinuation (Anastos et al., 2005; Ickovics et al, 2001)  Psychotherapy, pharmacotherapy or combination of both can be used to treat depression  Self-care strategies for management of depressive symptoms used effectively by people with HIV include prayer, meditation, talking to others, using distraction, and exercise (Eller et al., 2005)

50. HIV and Pregnancy (1)  80% of HIV+ women are of childbearing age; consider in ART regimen selection  Care should include routine, regular education and counseling about pregnancy/ contraception  Assess for factors associated with unplanned pregnancies  substance abuse by the woman or her partner  mental illness  domestic violence

51. HIV and Pregnancy (2)  About 1/3 of HIV+ women and men receiving medical care in the US desire children in the future (Chen, 2001)  20% of serodiscordant couples would practice unsafe sex in order to conceive (Klein, 2003)

52. HIV and Pregnancy: Counseling (1)  Impact of HIV on pregnancy course/outcome  Impact of pregnancy on HIV progression  Other reproductive issues based on maternal factors  coexisting drug/alcohol use  advanced maternal age  hypertension, diabetes (Anderson, 2005)

53. HIV and Pregnancy: Counseling (2)  General preconception issues  nutritional counseling (e.g. folic acid)  importance of early and intense prenatal care  Long term health of mother and care for children (guardianship issues) (Anderson, 2005)

54. HIV and Pregnancy: Counseling (3)  Perinatal transmission  Use of antiretrovirals and other medications in pregnancy  Safe conception if partner HIV-negative (Anderson, 2005)

55. HIV and Pregnancy: Studies (1)  Meta-analysis: 7 studies of effects of pregnancy on HIV disease; no overall significant differences in  death  HIV disease progression  progression to an AIDS-defining illness  fall in CD4 count to below 200/mm 3 (French, 1998)

56. HIV and Pregnancy: Studies (2)  Study of pregnancy on HIV disease progression In women with repeat pregnancy (n=329), compared to those with only one pregnancy (n=953)  There was no difference observed in:  viral load  CD4  clinical disease progression (Minkoff et al., 2003)

57. Pregnancy and ARV Treatment: Study  Contributions of maternal factors to adverse pregnancy outcomes in HIV+ women on ART  N = 497 HIV+ pregnant women  adverse pregnancy outcomes were  pre-term birth,  low birth weight  intrauterine growth retardation  Pregnancy outcomes similar to those reported for uninfected women of similar race/ethnicity who received adequate prenatal care (Lambert, 2000)

58. Pregnancy and ARV Treatment (1)  Goals in use of ARVs during pregnancy  treatment of maternal infection  reduction in the risk of perinatal transmission  Pregnant women who meet criteria as for other adults and adolescents  offer standard combination ARV therapy  two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI) (excluding efavirenz) (Anderson, 2005)

59. Pregnancy and ARV Treatment (2)  Considerations for ARV treatment decisions: (Anderson, 2005)  Treatment recommendations for health of the woman  Current information re effectiveness of ART in reducing perinatal transmission  Known or potential effects of ARV drug exposure on the pregnant woman  Known or potential effects of ARV drug exposure on the fetus/newborn  importance of adherence to any prescribed ARV regimen

60. Pregnancy and ARV Treatment (3)  Considerations re prevention of mother-to- child transmission (PMTCT) and maternal and fetal safety influence  timing of initiation of treatment  selection of regimens NOTE: Curriculum of the WHO and HHS/CDC Prevention of Mother-to-Child Transmission of HIV (PMTCT) Generic Training Package (CDC, March, 2006) is available at http://www/cdc.gov/nchstp/od/gap/pmtct/

61. Pregnancy and ARV Treatment (4)  Drugs that cause GI upset  may not be well tolerated in early pregnancy when morning sickness is common  may increase risk for non-adherence  may have inadequate blood levels from vomiting  All ARVs should be discontinued and restarted when the nausea and vomiting is gone or effectively treated

62. Pregnancy and ARV Treatment (5)  Pregnant women starting ARV therapy should not be offered nelfinavir-containing regimens  Pregnant women with alternative treatment options should be switched to another drug  Nelfinavir should be avoided in HIV-infected women who are planning to become pregnant  The drug has been found to contain ethyl methanesulfonate (EMS), a chemical that is potentially carcinogenic in humans

63. Pregnancy and Nevirapine (1)  Potential side effects of nevirapine in pregnancy  Women, esp. with CD4 counts >250/mm 3, are at increased risk for symptomatic, rash- associated, nevirapine-related hepatotoxicity  Deaths from hepatic failure reported  Early non-specific symptoms of hepatotoxicity can be confused with symptoms common in pregnancy

64. Pregnancy and Nevirapine (2)  Potential side effects of nevirapine in pregnancy (cont.)  Women should be monitored for clinical symptoms and hepatic transaminases (i.e., ALT and AST), particularly during the first 18 weeks of therapy, when this toxicity is most likely

65. Pregnancy and Protease Inhibitors (1)  PIs are associated with development or worsening of hyperglycemia or diabetes  Pregnancy also increases risk for glucose intolerance  It is not known conclusively whether the use of PIs in pregnancy will exacerbate risk for development of gestational diabetes

66. Pregnancy and Protease Inhibitors (2)  For women receiving PIs in pregnancy  monitor glucose levels  ask regularly about symptoms of hyperglycemia.

67. Lactic acidosis and Hepatic steatosis (1)  Lactic acidosis and hepatic steatosis (fatty liver)  may have higher incidence in women  thought to be due to damage to mitochondrial DNA (mitochondrial toxicity) that is caused by long-term nucleoside analogue use (Arenas-Pinto et al, 2003; McComsey & Lonergan, 2004)

68. Lactic acidosis and Hepatic steatosis (2)  Several maternal deaths due to lactic acidosis/hepatic steatosis  All were in women receiving combination of d4T/ddI as part of their ART at the time of conception and for the duration of pregnancy  Non-fatal cases of lactic acidosis have also been reported in pregnant women receiving this combination

69. Lactic acidosis and Hepatic steatosis (3)  Early symptoms of mitochondrial dysfunction are nonspecific and mimic symptoms of pregnancy  nausea and vomiting  abdominal pain  dyspnea  weakness

70. Lactic acidosis and Hepatic steatosis (4)  Pregnant women receiving nucleoside analogue drugs (NRTIs)  should have liver enzymes and electrolytes evaluated more frequently during the last trimester of pregnancy  should have new symptoms evaluated promptly and thoroughly

71. Assessment and Counseling (1)  Women infected with HIV may have more difficulty accessing health care due to:  Fear of disclosure  Lack of financial resources  Lack of transportation  Burden of caring for others, especially children

72. Assessment and Counseling (2)  Women often have difficulty negotiating protective sex due to power differentials  Lack of power may cause women to:  Have sex against their will  Have sex without a condom, against their will (CDC, May 2006)

73. Assessment and Counseling (3)  Lack of power may cause women to (cont.) :  Have sex with a man without knowing whether he has high-risk behaviors (unprotected sex with men, sex with many other partners, injection drug use)  Trade sex for drugs or money  Be unable to talk to their partners about abstinence, faithfulness, and condom use (CDC, May 2006)

74. Assessment and Counseling (4)  Support system: At initial visit and at intervals assess woman’s support system  Who knows her HIV status  Problems encountered with disclosure  Family and/or friends to whom she turns for ongoing support  Barriers to disclosure to sexual or needle- sharing partners

75. Assessment and Counseling (5)  Contraception:  Discuss method of contraception  If pregnant, discuss postpartum contraceptive plans  Educate and counsel about available options to permit informed decision making  Condom use:  Review sexual activity at each visit  Reinforce condom use

76. Assessment and Counseling (6)  Drug use/treatment: At initial visit and at intervals assess past/current substance abuse (tobacco, alcohol, illicit drugs)  Type of substance(s)  Amount of use  Route of administration  Prior drug or alcohol treatment  Counsel about specific risks associated with substance abuse in pregnancy. Treatment should be encouraged and facilitated for active problems

77. Assessment and Counseling (7)  Adherence: Assess and reinforce importance of adherence to prescribed medications before they are initiated and at each visit  Clinical trials: Inform about the availability of and offer participation in clinical trials for which woman is eligible

78. Assessment and Counseling (8)  Advance directives: Discuss advance directives for care in the event of sudden deterioration in the woman’s health  Discuss guardianship plans for children in the event of the mother’s incapacitation or death  Facilitate legal assistance, if needed

79. Key Points (1) 1. The proportion of AIDS cases in women has increased from 8% in 1985 to 27% in 2004. 2. Women of color are disproportionately infected with HIV. 3. HIV’s effect on estrogen, progesterone and testosterone leads to multiple symptoms.

80. Key Points (2) 4. HIV+ women are less likely than HIV+ men to receive HAART. 5. Avoid efavirenz in pregnant women and those at risk for pregnancy. 6. NRTI and PI-related lipodystrophy 2X more common in HIV+ women vs. HIV+ men.

81. Key Points (3) 7. Contraception  Hormonal contraceptives: no sig. effect on CD4+ count, viral load, response to HAART  IUD may increase menstrual flow, transmission risk, anemia 8. Negative consequences of stigma include  Fear of disclosure and identification as HIV+  Isolation; reduced social support  Reduced access  Reduced adherence

82. Key Points (4) 9. Supportive and unsupportive social interactions should be assessed. 10. HIV and pregnancy  Assess risk for unplanned pregnancy  Counsel re impact of HIV on pregnancy and pregnancy on HIV disease  ARVs (treat maternal infection; PMTCT)  potential side effects of nevirapine, PIs  lactic acidosis, hepatic steatosis

83. Key Points (5) 11. Assess and counsel regarding:  Support system  Contraception  Condom use  Drug use and treatment  Adherence  Clinical trial availability  Advance directives  Guardianship  Legal assistance