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Providing Care for HIV-Infected Women

Providing Care for HIV-Infected Women. Amneris E. Luque, MD SMH AIDS Center Medical Director. AIDS Incidence* for Women and Percentage of AIDS Cases: US, January 1986-June 1999. 8000. 30. 25. 6000. 20. Cases of AIDS in Women. 4000. 15. Percent of All Cases. 10. 2000. 5. 0. 0.

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Providing Care for HIV-Infected Women

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  1. Providing Care for HIV-Infected Women Amneris E. Luque, MD SMH AIDS Center Medical Director

  2. AIDS Incidence* for Women and Percentage of AIDS Cases:US, January 1986-June 1999 8000 30 25 6000 20 Cases of AIDS in Women 4000 15 Percent of All Cases 10 2000 5 0 0 1990 1993 1986 1987 1988 1989 1991 1992 1994 1995 1996 1997 1998 1999 Half-Year of Diagnosis* *Adjusted for reporting delay.

  3. AIDS Cases and Rates inAdult/Adolescent US Women:by Race/Ethnicity, 1999 Rate per Race/Ethnicity N (%) 100,000 White, not Hispanic 1924 (18) 2 Black, not Hispanic 6784 (63) 49 Hispanic 1948 (18) 15 Asian/Pacific Islander 63 (1) 1 American Indian/ Alaska Native 40 (<1) 5 Total* 10,780 (100) 9.3 *Includes 21 women of unknown race/ethnicity.

  4. AIDS in US Women:Rate per 100,000, by State, 1999 2.1 * 2.0 * * 1.8 1.7 1.2 1.2 NH 1.3 30.0 1.6 14.8 MA 2.5 3.4 RI 7.2 9.2 1.2 CT 13.0 1.9 1.8 4.6 19.6 NJ 2.0 2.1 5.5 2.1 0.9 14.1 DE 2.5 7.4 5.2 MD 21.0 2.7 3.6 93.4 DC 6.7 5.9 1.5 0.9 4.7 3.0 15.0 Rate per 100,000 <5 6.3 9.1 13.4 _ 7.4 5 9.9 11.0 10+ 23.2 * * <5 cases VI 30.1 PR 21.3 1.6 US rate: 9.3 N=10,780

  5. HIV in Women • Initially acquired through IVDU • 1991-Heterosexual contact with IVDU or bisexual partner • 1995- Heterosexual partner not in a high risk group

  6. Risk Factors for Increased Heterosexual Transmission of HIV • Presence of ANY other STD in HIV negative partner • Anatomic factors • Sexual practices

  7. Risk Factors for Increased Heterosexual Transmission of HIV • HIV disease stage in HIV+ partner • Certain HIV clades • Use of hormonal contraceptives

  8. HIV in Women • Disease characteristics • Impact of pregnancy on HIV disease • Impact of HIV disease on fetal outcome

  9. Demographics of HIV-infected Women in US • Age 15-44 years • Majority are from racial/ethnic minority groups • 64% live in households with incomes < 10K/year • 23% live alone, 2% live in facilities 1% are homeless

  10. Access to Health Care in HIV-infected Women • Several studies have shown that women are less likely to receive ARV and to be admitted for AIDS related conditions than men • Family and child care obligations may preclude access to care • HCW less familiar with HIV diseasein women

  11. Is HIV Different in Women? • The Viral load debate • Early in infection lower viral loads than men at similar CD4 counts • Survival and disease progression appear to be similar to men • Further studies are needed

  12. Initial Manifestations of HIV infection in Women • The most common is recurrent candida vaginitis (37%) • Generalized lymphadenopathy (15%) • Bacterial pneumonia (13%)

  13. Other Gynecological Infections • PID tends to be more severe • HSV infections are common • Bacterial vaginosis more frequent than in HIV- • Syphilis

  14. Menstrual Abnormalities • Amenorrhea • Lower CD4 count • Low serum albumin • Heroin use • Other menstrual irregularities • Not clearly different from HIV- • Report of menorrhagia in 4 women on RIT

  15. Toxicity of ARV in Women • Women more likely to experience nausea and perioral paresthesias with RIT • More abdominal pain with NFV • Higher incidence of rash with DLV

  16. Toxicity of ARV in Women • Higher incidence of hepatotoxicity with NVP • Different patterns of fat redistribution with ARVT • More frequent increase in abdominal girth • More frequent increase in breast size

  17. Toxicity of ARV in Women • Steatosis and death with use of stavudine plus didanosine during pregnancy.

  18. Interactions Between ARV and Ethinyl Estradiol

  19. AIDS-defining illnesses in women • Similar spectrum than in men • Two exceptions: • Kaposi’s sarcoma • Cervical cancer

  20. Cervical Cancer in HIV-infected Women • More aggressive disease • 40-60% more likely to have relapses

  21. HPV in HIV-Infected Women Study Amneris E. Luque, Lisa M. Demeter, Heng Li and Richard C. Reichman

  22. Study Design • HIV-infected women obtaining their care at the University of Rochester’s AIDS Center. • Longitudinal study of HPV infection in HIV-infected women. • 204 non-pregnant women with documented HIV infection gave informed consent

  23. Study Design • Subjects who were menstruating at the time of the study visit or had a history of hysterectomy were excluded (n=16) • All participating subjects underwent : • Standardized history and physical examination • Gynecological questionnaire • Pelvic examination

  24. Study Design • Pelvic examination: • PAP Smear: Cervex-Brush® • Cervical cultures for N. gonorrheae and C. trachomatis • Cervical sampling for wet mount preparation. • Cervical sampling for HPV DNA.

  25. Virological Studies • HIV-1 RNA Roche’s Amplicor® Assay • HPV DNA DIGENE® Hybrid Capture Assay • Low risk HPV: (LR HPV): HPV 6, 11, 42, 43, 44 • High risk HPV: (HR HPV): HPV 16, 18, 31, 33, 35, 45, 51, 52, 57 • HPV Serology: ELISA, using VLP

  26. Results-Cross Sectional Study • HIV-1 RNA levels > 10,000 are associated with presence of oncogenic HPV and abnormal Pap smears Luque AE, Demeter LM and Reichman RC. JID 179:1405-9, 1999

  27. Results-Cross Sectional Study • Abnormal Pap smears were associated with HIV-1 RNA > 10,000 copies/ml P = 0.0016 • Oncogenic HPV was strongly associated with abnormalities in Pap smear P = < 0.001 Luque AE, Demeter LM and Reichman RC. JID 179:1405-9, 1999

  28. HPV inn HIV-infected Women • Pap smear results (n=191) • 123 (64%) normal • 31 (16%) ASCUS • 25 (13%) LGSIL • 7 (4%) HGSIL • 3 (2%) dysplasia nos

  29. HPV in HIV-infected Women • ARVT • At baseline: • 104 (51%) were on ARV • 37 (18%) were on 2 NRTI • 61 (30%) were on 2 NRTI + PI • 6 (3%) were on 2NRTI + NNRTI

  30. Pap Smears and Cervical HPV DNA Results in 108 Women at Enrollment and F/U Visits According to ARVT

  31. Pap Smear Results at F/U Visit,According to ART in 34 Women With Abnormal Pap Smears at Enrollment 100 P<.03 87% 80 60 ART 53% No ART 47% 40 20 13% 0 Normal Abnormal Luque. 8th CROI; 2001; Chicago. Abstract 724.

  32. HPV DNA in Cervical Samples at F/U Visit, According to ART, in 53 Women With HPV DNA– at Enrollment P<.01 80 80% 78% 60 ART 40 No ART 20 22% 20% 0 HPV DNA+ HPV DNA– Luque. 8th CROI; 2001; Chicago. Abstract 724.

  33. Conclusions • In this study women receiving ARVT were more likely to have a normal Pap smear than women not receiving ARVT • Among women who had an abnormal Pap smear at enrollment, those on no ARV were more likely to continue to have an abnormal Pap smear at the F/U visit than those on ARV P = 0.03, OR: 0.17, 95% CI: 0.03-0.97

  34. Conclusions • Women receiving ARVT were less likely to have HPV DNA detected on their cervical samples at the first F/U visit than women not receiving ARV. P = <0.01, OR: 0.07, 95% CI; 0.013-0.416 • These differences remained significant after adjusting for HIV-1 plasma level and CD4 counts

  35. Influence of Pregnancy on HIV Infection • 32 women (SHCS) compared to 416 controls • Recurrent bacterial pneumonia only AIDS defining illness that was SS • Inconsistent acceleration of disease progression Weisser M, Rudin C, et al. J Acqu Imm Def Hum Ret 1998;17:404-410

  36. Vertical transmission • Intrauterine • Peripartum • Postpartum

  37. Vertical Transmission • Intrauterine • HIV in fetal organs (PCR) • HIV detected as early as 10th weeks gestation • Placental infection • Corioamnionitis

  38. Vertical Transmission • Peripartum • HIV in cervico-vaginal secretions • Discordant infections in twins • Less genetic diversity in viral strains of the newborn compared to maternal strains

  39. Vertical Transmission • Intrauterine • Peripartum • Postpartum • Breast milk

  40. Risk Factors in Vertical Transmission • High maternal plasma and genital tract virus load • Advanced maternal clinical HIV-1 disease stage • Reduced maternal immunocompetence

  41. Risk Factors in Vertical Transmission • Vaginal delivery • Lengthy interval between rupture of amniotic membrane and delivery • Prematurity and low birth weight

  42. Prevention of Vertical Transmission

  43. ACTG 076 • ZDV 500 mg/day starting at week 14-34 • ZDV during labor 2mg/Kg over one hour followed by ZDV 1mg/Kg until delivery • ZDV to the newborn 2 mg/Kg q 6 h for 6 weeks starting 8-12 h after birth

  44. DHHS Recommendations • To inform the results of ACTG 076 to all HCW and all HIV + patients • To inform HIV + patients that the risk of transmission is reduced but not eliminated • Caution not to use ZDV before week 14 of pregnancy

  45. ZDV during Pregnancy • ZDV crosses the placenta • ZDV is well tolerated by the newborn • Macrocytic anemia most common adverse effect

  46. Time of ZDV No. of Infants Positive PCR Relative Risk N (%) 95% CI Prenatal 423(45) 26 (6) 4.1-8.9 0.23 (0.16-0.34) Intra-partum 50(5.3) 5 (10) 3.3-21.8 0.38 (0.18-0.81) Within 48 h after birth 86 (9.2) 8 (9.3) 4.1-17.5 0.35 (0.19-0.65) >3d after birth 38 (4) 7 (18.40 7.7-34.3 0.69 (0.35-1.36) No ZDV 237 (25) 63 (26.6) 21-32.7 1 Abbreviated ZDV Prophylaxis and Perinatal Transmission Wade N, Birkhead G et al NEJM 1998: 339-1409-14

  47. Recommendations • Offer ZDV intrapartum to HIV+ women who did not take prenatal ZDV • Initiate testing for identification of HIV+ women during labor-48h after delivery using rapid testing to implement prophylaxis

  48. Vertical TransmissionHIVNET-012 • 311 women in Uganda received single dose NVP (200 mg PO) at onset of labor • Infants received NVP within 72h • Compared to ZDV • NVP 47% more effective than ZDV in decreasing Vertical transmission Guay LA, Musoke P, Fleming T et al Lancet 199;354:795-802

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