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New Developments in HIV Care for Women

New Developments in Epidemiology

The proportion of cases among women has increased dramatically from 1993 to the present. Each year the proportion of cases has increased steadily, with women constituting a larger amount of the total cases. In 1995 women constituted 19% of the total cases for that year and as of December 2006 the number rose to 20%.

Heterosexual Transmission (HT)

The incidence of AIDS has increased more in women in the last few years because of increases in heterosexual transmission in women.

Male IDUs are the main reservoir for heterosexual transmission in women.

In 1995 heterosexual contact was the dominant mode of transmission for the majority of women in almost all regions of the U.S. (58% in the South, 52% in the West)..

Heterosexual Transmission of AIDS Among Young Women

Probably the most alarming trends are in young women ages 13-25. It is estimated that 20% of younger adults will progress to AIDS within 5 years; they are considered rapid progressors.

In the year ending in 2006, HT was the mode of transmission in 51% (362) of all the infections in women ages 20-24. In young men of the same age group, it accounts for 7% (79) of infections. These trends are similar among even younger women ages 13-19.

These trends are important to note. They are markers for increased transmissibility in young women due at least partially to cervical ectopy as well as underlying social inequities. In young women the thin columnar cells of the cervical transition zone are more exposed than in older women making transmission of HIV easier.

Adolescent women are becoming infected by older men.

Classification of Heterosexual Transmission

Heterosexual Transmission requires a history of heterosexual contact with a partner who has HIV infection, AIDS or risk factors for HIV infection (IDU, hemophilia, etc). This implies that if you say you got AIDS from heterosexual contact that you know about these risk factors in your partner. This is not true for many of the women who develop AIDS.

Disproportionate Amounts of AIDS in Women of Color

Twelve percent of all women in the U.S. are African-American.

As of December 2006, 56% of all the women with AIDS were African-American.

Three of the five cities with the highest incidence of AIDS are located within 70 miles of each other. In southern Florida, AIDS strikes black non-Hispanic women even more disproportionately. Not surprisingly, the bulk of these women are poor and receive care in the public health system.

What is Driving the Particular Epidemiology in Florida? Why is Prevention Difficult and Complex?

In southern Florida HIV transmission is associated with crack cocaine and IDU. High-risk sex with multiple partners is often a byproduct.

This area of Florida represents a broad cultural mix of individuals from Latin America as well as the Caribbean. Cultural differences may have a significant effect on driving the epidemiology.

Open discussion of sex often is taboo. Homosexuality and bisexuality are akin to heinous crimes and open acknowledgment of homosexuality or bisexuality is uncommon.

Gender Differences

Heterosexual Transmission

The UN estimates that 2/3 of infected women worldwide may have had only their own husbands as sexual partners. Many other observations support the concept that the number of sexual partners may not be the major factor in male to female transmission in North America but the risk is a relationship with one HIV positive man.

Results in cross sectional studies of couples consisting of discordant partners are fairly consistent in reporting

What is Driving Greater Male to Female Transmission?

1.    There is increased virus in semen and an increased volume of semen versus vaginal secretions.

2.    The surface areas of the vagina and cervix are much greater than the male urethra

Natural History -So What's Different?

1.    Gynecologic issues are a large domain of women and AIDS with women having a great deal more morbidity from gynecologic issues than one might appreciate.

D.    Non-Gynecological Differences

1.    Benson from Rush notes that major differences included the greater incidence of candida infections of other mucosal surfaces, especially the esophagus. Candida esophagitis has been increasing in frequency as the epidemic has increased. All studies of women have found it to be quite common. Before 1993 it was the number

E.    Skin Manifestations of HIV and Differences between Men and Women

1.    Seborrheic dermatitis is the most common skin condition. In men it is common on the face, chin, nasal area, auditory canal, and axilla.

2.    In women it appears in the axilla, between the breasts, in the groin and occasionally in the external ear.
F.    Kaposi's Sarcoma

1.    It is the initial presentation in 30% of all people with AIDS but is found in less than 2% of women. More commonly described in homosexual men and bisexual men, it is also described in women having sex with bisexual men.

G.    Progression and Survival Differences

1.    Results of initial early studies analyzing survival suggested there was a difference based on gender. Regardless of the risk group or race many early studies indicated that the prognosis for women was worse than that for men.

2.    All of the more recent work disputes this and supports the contention that those results were just markers.
H.    Use of Antiretroviral Therapy in Women
1. Disappointingly there is still a paucity of data about efficacy and toxicity of antiretroviral drugs in women. Initial studies of AZT did not include women. Although more recent studies have sought participation from women their participation is still low.2.    Cotton and colleagues present data from 1987-1990 when women accounted for 6.7% of 11,909 ACTG clinical trial participants. Most of the women were Caucasian and only 22.6% were IDU's.
I.    OI Prophylaxis and CMV Antibody Screening

1.    Appropriate OI prophylaxis is necessary for both women and men and no gender specific recommendations can

III.    Lesbian, Bisexual Women and WSW (Women having Sex With Women)

A.    Transmission of HIV

1. The myth circulating is that lesbians are at no risk for contracting AIDS.

2.    Lesbians and bisexual women are a very heterogeneous group with a wide variety of lifestyles and behaviors. Sexual identity is often not a good marker for sexual behaviors.

3.    HIV transmission depends only on behaviors and not any particular sexual identity.
4.    Transmission of HIV between women was documented as early as 1984.

1.    The survey examined 498 lesbians and bisexual women 17 years or older randomly sampled at 25 public locations in San Francisco and Berkeley.

2.    Results: The study found that 1.2% of lesbians and bisexual women were infected with HIV, 5.4% had markers for hepatitis B and 0.4% had markers indicating a history of syphilis. The prevalence of HIV infection in this population is more than 3 times higher than that estimated for all adults or adolescent women in San Francisco (0.35%).

3.    Lesbians and bisexual women reported high levels of injection drug use and unsafe sex behaviors with male.

IV: HIV and Pregnancy

A.     Pregnancy and Its Effect on HIV

1.    Pregnancy itself has an immunosuppressive effect on all women with an expected decline in CD4 lymphocytes.
2.    Preliminary studies indicate that CD4 counts take longer to return to pre-pregnancy levels in HIV infected women. Most studies in industrialized nations suggest that being pregnant does not accelerate asymptomatic HIV disease. There are no more miscarriages or other pregnancy complications among asymptomatic HIV infected.

B. Transmission of the Virus

1.    The vast majority of infections result from vertical transmission during pregnancy, delivery or breast-feeding.

2.    Virus has been isolated in the conceptus and in the anmiotic fluid at all times during the pregnancy.

3.    Increased rates of transmission are associated with high viral load, P24 antigenemia, increased CD8 counts, low CD4, placental membrane inflammation, placental membrane rupture for greater than 4 hours, maternal fever.
C.    AZT and Pregnancy

1.    AZT appears to limit the transmission of HIV to fetuses.

2. NIAID ACTG 076 study started in August 1991. The original data published included (364) mothers at 50 U.S. sites and 9 French sites. All women had > than 200 T-cells and were antiretroviral negative.3.    100 mg of AZT five times a day or 200 mg three times a day was given between the 14th and 34th weeks of pregnancy. During labor

D.    Toxicity of AZT?

1.    AZT can interfere with DNA polymerase, and increased rates of cancer (liver and vaginal) have been seen in
E.    What other types of ARV Therapy Can be Used During Pregnancy?

1.    This is clearly an area where a paucity of data exists but still recommendations can be made.

2.    Recent data suggest that both AZT and 3TC and the new non-nucleoside reverse transcriptase inhibitor
F.    New Recommendations for Pregnant Women
1.    Assess the CD4, viral load and clinical indicators to determine the optimal antiretroviral medications.
G.    If the Pregnant Woman Has No Prior Use of ARVs

1.    Discuss the risks and benefits of starting therapy before or after the 14th week of gestation.

2.    Select a combination of medications that is appropriate for her given CD4 count, viral load and clinical status. Include AZT as part of that regimen.
V. Gynecologic Issues

A.    Routine Gynecologic Care

1.    Baseline colposcopy at HIV diagnosis if available.

B.    Counseling

1.    Should include information on STDs, cervical cancer, HPV, contraception, pregnancy and safer sex.
C.    CIN and HPV

1.    HPV has been investigated as an etiologic factor in human and cervical cancer since the 1970s. Approximately 95% of cervical condyloma, all grades of CIN and invasive cervical cancer contain HPV~DNA.

D.    Abnormal Cervical Cytology and immunosuppression

1.    Data collected through the WIHS on 2054 HIV infected women and 568 seronegative controls shows a 40% prevalence of abnormal Pap smears in HIV infected women versus 17% prevalence in the seronegative women. Abnormal PAP smears include ASCUS (atypical squamous cells of undetermined significance).

E.    Sensitivity of Pap Smears

1.    Pap smears appear to be approximately 75-90% sensitive in studies looking at immunocompetent women. In immunocompetent populations dysplasia is often extremely slow before progression to cervical cancer occurs. The Pap smear is a reasonable screening test.

F.    Treatment of CIN

1.    CIN I that is documented on biopsy (not just Pap smear) does not appear to progress to invasive cervical cancer. It does need to be followed to ensure that it doesn't progress to a higher grade of CIN.

G.    Vaginal Candidiasis

1.    Can occur across the whole spectrum of early to late HIV disease. Many women, with HIV, even with late stage disease, do not experience VC.

H.    Persistent Ulcerative Lesions

1. Rule out syphilis, chancroid, HSV, and ulcerative candidiasis.

2.    Perform RPR and Dark Field exam (even if patient has non-reactive RPR); bacterial culture and sensitivity.

I.    Acute Herpes Simplex

1.    Augenbraun recently demonstrated that HSV-2 shedding was nearly four times greater in HIV+ than in HIV- women.

2.    Schacker demonstrated in 12 HIV infected men with recurrent HSV and HIV, consistent HIV in the HSV lesions with many containing 5,000 or more copies of HIV RNA per sample. There is every reason to assume this occurs.

J.    PID

1.    Presentations are not substantially worse in HIV+ women.2.    Serious infections can present with normal white blood cell counts. Remember that baseline white cell counts for patients with AIDS may normally be 2.0- 3.5 X 109

L.    Menstrual Irregularities

1.    It has been suggested that HIV infected women experience higher rates of menstrual irregularities including amenorrhea, menorrhagia, intermenstrual bleeding and worse PMS.

2.    Some small studies (not all well controlled) suggest bleeding abnormalities in 1/3 of patients, with either amenorrhea or excess bleeding. A New York study of IDUs compared 39 HIV+ and 39 HIV- women.
VII. Referral for HIV Counseling and Testing

A. Possible immunosuppression must be considered with the following gynecologic conditions:

1.    Recurrent genital herpes simplex (more than 2 episodes within 6 months).