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Human Immunodeficiency Virus in Women. Lori E. Kamemoto, MD, MPH Department of Obstetrics, Gynecology and Women’s Health University of Hawaii. HIV in Women. 1. Epidemiology 2. Sexual Transmission and post- exposure prophylaxis 3. Contraception 4. Gynecologic problems

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human immunodeficiency virus in women

Human Immunodeficiency Virus in Women

Lori E. Kamemoto, MD, MPH

Department of Obstetrics, Gynecology and Women’s Health

University of Hawaii

hiv in women
HIV in Women

1. Epidemiology

2. Sexual Transmission and post-

exposure prophylaxis

3. Contraception

4. Gynecologic problems

HPV disease

hiv in women1
HIV in Women

USA: 24% of all AIDS cases are women (1999)

Hawaii: 8% of all AIDS cases are women (1994-9)

Worldwide: more than 40% of all adult HIV infections are women (75% of all new infections)

aids in women u s
AIDS in Women, U.S.

Estimated 1,080 50+ AIDS cases in 1996

CDC, 1998

most common aids indicator diseases in women
Most Common AIDS-indicator Diseases in Women

*some with more than one diagnosis, CDC, 1992

sex differences in hiv
Sex Differences in HIV
  • Women have a lower viral load than men
  • Time to development of AIDS was similar in men and women
  • Women with the same viral load as men had a higher risk of AIDS (OR = 1.6, 95% CI 1.1-2.32)
  • Suggests that viral load recommendations for antiretrovirals may need to be revised downwards for women

Farzadegan, etal. Lancet, November 7, 1998

hiv infection in women sexual transmission
HIV Infection in WomenSexual Transmission

Homosexual

Men

Men infected by

Blood products

Male IVDU

Bisexual

Men

Infected Sperm

Donors

WOMEN

Homosexual

Women

hiv prevention key strategies
HIV Prevention Key Strategies
  • Prevent HIV
  • Determine HIV status
  • Treat HIV as early as possible
barriers to hiv testing in women
Barriersto HIV Testing in Women
  • No prenatal care (15% of HIV+ have no prenatal care)
  • Heavy clinic load
  • When health care providers strongly recommend testing (routine prenatal test), patient 3 times as likely to get tested
  • Patient afraid of testing

Ickovics, 1999

sexual transmission of hiv
Sexual Transmission of HIV
  • Probability of HIV transmission with vaginal intercourse: 0.1%
    • Women about twice as susceptible to heterosexual transmission of HIV than men
  • Probability of HIV transmission with anal intercourse: 0.5-3%

Lurie, JAMA, 1998

hiv in the female genital tract
HIV in the Female Genital Tract
  • HIV detected in cervicovaginal secretions and cervical tissue
  • Increased rate of cervical HIV shedding with cervical ectopy, cervicitis, pregnancy, oral contraceptives and increased serum viral load
  • Decreased genital tract HIV with anti-retrovirals

Critchlow CW, OBGyn Survey 1997

chlamydia and hiv transmission
Chlamydia and HIV Transmission
  • Chlamydia may increase susceptibility to HIV
  • Prostitutes with Chlamydia cervicitis had a 3 times higher risk for HIV seroconversion
  • Chlamydia causes mucosal friability, bleeding and an inflammatory response

Laga M. Sixth Int’l Conf on AIDS, 1990

male circumcision and hiv infection risk
Male Circumcision and HIV infection Risk
  • Thirty studies reviewed
  • 22 studies reported a significant association between circumcision and HIV + status (RR 1.5 - 8.4)

(4 studies with a trend towards association and 4 studies with no association)

Moses. STD 1994

depoprovera and hiv transmission
DepoProvera and HIV Transmission
  • 1996 - SIV contracted by 14/18 monkeys on progesterone implants
    • 1/10 not on implants implants HIV infected
  • Hypothesis: thinning of the monkeys’ vaginal epithelium increased risk of transmission
  • Martin (Kenya) - women on DepoProvera had an increased risk of HIV infection (OR 2.2, 95% CI 1.3-3.1)
  • Other human studies show no increased risk

Martin HL. J of Inf Dis, October 1998

vaginal microbicides
Vaginal Microbicides
  • Need to develop methods that a woman can control to help prevent sexual transmission of HIV
  • Various vaginal microbicides are currently being studied
needlestick injuries to health care workers
Needlestick Injuriesto Health Care Workers
  • HIV

-22 published studies

-0.25% (1 in 400) risk of seroconversion

from needlestick

-0.09% (1 in 1,000) risk of seroconversion from mucous membrane exposure

-chemoprophylaxis is the standard of

care

  • Hepatitis B: 5-60% chance of infection
hiv postexposure prophylaxis
HIV Postexposure Prophylaxis
  • NO randomized studies exist
  • Biologically plausible
  • Scientific evidence

animal models

ARV prophylaxis in pregnancy studies

support PEP

hiv postexposure prophylaxis after sexual contact
HIV Postexposure Prophylaxis after Sexual Contact
  • Probability of HIV transmission

with vaginal intercourse 0.05-0.15%

anal intercourse 0.8-3.2%

  • If the partner’s HIV status is known, recommend prophylaxis
  • If the partner’s HIV status is unknown, decision based on type of exposure and likelihood of HIV in the partner
  • Several probable cases of HIV transmission from rape reported

Katz. JAMA 1997

postexposure prophylaxis after non occupational hiv exposure
Postexposure Prophylaxis afterNon-occupational HIV Exposure

“The probability of HIV transmission by certain sexual or injection drug exposures is of the same order of magnitude as percutaneous occupational exposures for which the CDC recommends PEP.”

“In such cases, if the exposure is sporadic, it seems appropriate to extrapolate from the data on occupational PEP and recommend prophylaxis”

JAMA 1998

assessing risk of hiv transmission after non occupational exposure
Assessing Risk of HIV Transmission after Non-occupational Exposure

Probability of HIV infection depends on:

  • frequency of exposure
  • probability that the source is HIV +
  • probability of infection if the source is

HIV +

hiv infected women sexual behaviors
HIV infected WomenSexual Behaviors
  • Heterosexual activity in the last 6 months

HIV positive 65%

HIV negative 76%

  • Always use a condom with vaginal intercourse

HIV positive 63%

HIV negative 28%

Wilson TE. AIDS, April 1999 (WIHS)

emergency contraception
Emergency Contraception
  • Plan B: levonorgestrol
  • Must be taken within 72 hours of intercourse
  • 89% effective in preventing pregnancy
  • No studies on HIV infected women
birth control pills and antiretrovirals hiv women
Birth Control Pills and AntiretroviralsHIV + Women
  • Efavirenz increases estradiol levels (AUC  37%)
  • Nevirapine decreases estradiol levels (AUC 19%)
  • Ritonavir decreases estradiol levels (AUC 41%)
  • Nelfinavir decreases estradiol levels (AUC 47%)
  • Birth control pills may not be effective with certain antiretrovirals
depoprovera hiv women
DepoProveraHIV+ Women
  • No data on progesterone levels and antiretrovirals
  • DepoProvera and Antiretrovirals study currently in enrollment
  • Many HIV infected women choose this

method of birth control

iuds hiv women
IUDsHIV+ Women
  • Theoretical concern regarding increased risk of uterine infection and PID with immuno- compromised patients
  • African study seemed to validate safety in their population, however these patients were not followed long term
gynecologic problems and hiv
Gynecologic Problems and HIV
  • Severe, recurrent yeast vulvovaginitis

Rhoads: 24% of HIV+ women had chronic candidiasis

  • Severe, recurrent genital Herpes
  • Syphilis may follow an accelerated course
  • Human Papilloma Virus infections occur more frequently and are more severe
  • Trichomonas infections are more severe
  • PID possibly more severe
longitudinal study of hpv in hiv infected women
Longitudinal Study of HPV in HIV infected Women
  • Prevalence of HPV at baseline

HIV + 73%, HIV neg 43%

  • Prevalence of high risk oncogenic HPV at baseline

HIV + 32.5%, HIV neg 17%

  • HIV + women with lower CD4 counts had a higher prevalence of HPV
stages of hpv infection
Innoculation

Incubation period: HPV DNA establishes itself

Active lesion growth  3-6 months

 9 months from the time of the first lesion: equilibrium between lesion growth and host immune response  sustained remission or continued active lesions

Stages of HPV Infection
a shared etiology for all anogenital cancers
A Shared Etiology for all Anogenital Cancers?
  • Cancers associated with HPV infection
      • Cervical
      • Vulvar, vaginal
      • Anal
      • Penile
  • Common risk factors
      • Smoking
      • STDs, sexual activity
  • Factors that may not support shared etiology
      • Cervical cancer incidence peaks at age 40-50; other anogenital cancers continue to increase with age
      • Penile cancer does not seem to be increasing, slight increase in vulvar cancer, anal cancer increasing
anogenital dysplasia and hiv interaction between hiv and hpv
AnoGenital Dysplasia and HIVInteraction between HIV and HPV
  • HPV infection restricted to the epithelium and HIV infection primarily in the stromal cells/T-cells/Langerhans cells (1) and (2)
  • Pathogenesis theories
    • decreased cell mediated immunity to HPV
    • HIV and HPV may co-infect the same epithelial cells (3)
    • HIV infected cells may secrete factors that up-regulate HPV infection

Palefsky J, Monogr Natl Cancer Inst, 1998

anogenital disease and hiv immune response model
Anogenital Disease and HIVImmune ResponseModel
  • HPV infection acquired early with onset of sexual activity, followed by HIV
  • Early HIV infection: immunity relatively intact and no anogenital lesions
  • Late HIV infection: increased HPV levels and anogenital lesions

Palefsky J, Monogr Natl Cancer Inst, 1998

anogenital disease and hiv immune response model1
Anogenital Disease and HIVImmune Response Model
  • Restoration of immune response with HAART regression of HSIL
  • If HAART leads to prolonged life, but does not fully restore immunity to HPVcancer

Palefsky J, Monogr Natl Cancer Inst, 1998

gyn case presentation
23 year old G1 HIV+ woman who is 37 weeks pregnant and on combination ARVs

On pelvic examination, she is noted to have multiple condylomatous growths on the vulva

CD4=300 and viral load=8,000

Gyn Case Presentation
gyn case presentation1
Vulvar biopsy reveals condyloma

Cesarean section is performed

You ask her to follow-up in 3-4 months and on this visit, most of her condyloma has now disappeared

She is still taking her ARVs

A pap smear is done and you ask her to follow-up in another 3-4 months

Gyn Case Presentation
gyn case presentation2
Her pap smear revealed ASCUS

She complains of vulvar itching

Flat hyperplastic lesions are noted on the vulva

She was recently discharged from the hospital (PCP)

Gyn Case Presentation
gyn case presentation4
Biopsies reveal:

1. Cervical severe dysplasia, cannot rule out cancer

2. Vaginal biopsies reveal VaIN 1

3. Vulvar biopsies reveal

VIN 2-3

Procedures:

1. Cervical conization

2. Laser vulva

You ask her to follow-up in another 4-6 months

Gyn Case Presentation
gyn case presentation5
Another pap smear and colposcopy is done

You note that she still has a few residual vulvar raised lesions

A repeat pap smear and colposcopy is done

HPV disease waxes and wanes depending on patient immune status-HIV+ women need to be followed closely

Gyn Case Presentation
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