HIV Disease In Women

Pamela Juba, M.D.
Pam Juba, M.D. is an HIV specialist and Assistant Professor at the University of Florida
Health Science Center / Jacksonville. She is Associate Director of Adult Programs
of the Rainbow Center for Women, Adolescents, Children and Families.

Introduction

There is estimated to be between 120,000 to 160,000 women in the United States infected with HIV. Because HIV was perceived as a disease primarily affecting gay white men, the impact of this disease remained largely ignored. Despite more recent increased attention, needs assessment at all levels often either did not include women or had only token participation. HIV disease and many of the issues associated with it differ for men and women. HIV-infected women are less likely to know their CD4 cell counts or viral load, less likely to have access to health care or clinical trials, and less likely to receive current standard of care. The needs of women are different than men and in a recent survey of HIV-infected women conducted in Jacksonville, these differences were brought to the forefront.

Epidemiology

AIDS is affecting women at an increasing rate. In Florida, 38% of the reported HIV cases are in women, and in Duval County 35% reported heterosexual contact as the mode of exposure. Black women in Duval County are disproportionately affected comprising 79% of the AIDS cases and 86% of the female HIV cases. A majority of these cases were in women of childbearing age. Many women are diagnosed HIV-infected during their pregnancy.

Male to female sexual transmission of HIV infection is more efficient than female to male sexual transmission, primarily due to higher viral inoculum in the male ejaculate, longer periods of exposure to HIV infected fluids and larger surface area. Several factors increase the risk of transmission including sex during menses, sex with a partner with rapid progression of immunodeficiency, traumatic sex, and presence of systemic disease. Conditions that lead to inflammation of the vaginal epithelium or cervix such as ulcerative disease, infections with Gonorrhea, Chlamydia or Trichomonas exposes HIV-susceptible cells, primarily monocytes and lymphocytes, to infected fluid during intercourse. The presence of cervical ectopy exists in adolescents or in women on exogenous estrogens including oral contraceptives. HIV susceptible cells, submucosal Langerhan's, are present and can be exposed to HIV-infected semen during intercourse.^1,2

Barrier methods can dramatically reduce the risk of sexual transmission of HIV infection. Studies involving discordant couples (one partner is HIV infected, the other is not infected) have shown that using latex condoms substantially reduces the risk for HIV transmission.² The use of diaphragms or cervical caps are not effective in preventing transmission of infection.² Nonoxynol 9, a common spermicide, inactivates several pathogens in vitro such as Neis
seria gonorrhea, Chlamydia trachomatis, Haemophilus ducreyi, Treponoma pallidium, Trichomonas vaginalis, and the herpes simplex virus. It is only moderately effective in vivo against N. gonorrhea, C. trachomatis, and T. vaginalis. In a study performed using condoms and a nonoxynol 9 vaginal film there was no decrease in the transmission rate of HIV infection compared to the use of condoms alone.³

Education in the community and other prevention plans needs to be further developed and implemented to decrease the infection rate in women. A large proportion of infected women became infected during their adolescent years and early twenties. This age group continues to be a major segment of our population that needs to be targeted for prevention.

Gender Differences

Several studies have shown no differences in women when compared to men with regards to survival time or rate of progression to AIDS. However, a recent study demonstrated substantially lower HIV-1 viral loads in women at similar CD4+ counts when compared to men. The median viral loads were from 38% to 65% of those in men.⁴ Therefore, the risk of progression to AIDS in women is likely to be higher when comparing viral loads. Treatment recommendations and response to antiretrovirals are similar for men and women. Current guidelines recommend initiation of antiretroviral therapy with a CD4+ cell count < 500 or a viral load > 20,000 copies/ml. In patients with CD4+ cell counts > 500 or a viral load <20,000 copies/ml many experts recommend a postponement of antiretroviral therapy with close follow up. Women often continue to have very low levels of viral load despite continued loss of CD4+ cells. These differences need further study and better delineation and may lead to different criteria for developing guidelines for overall management and antiretroviral treatment in women.

Opportunistic infections and HIV related neoplasms by and large appear to occur at similar rates in women and men. Kaposi's Sarcoma does occur in women but with far less frequency than men. Presenting symptoms more commonly seen in HIV-infected women include wasting syndrome, severe herpes simplex virus infections (often requiring hospitalization) and genital tract disease.

Human Papillomavirus And Cervical Disease

Human papillomavirus (HPV), a common sexually transmitted virus is associated with genital warts and cervical dysplasia. Immunosuppression associated with HIV infection can accelerate or modify the clinical course of cervical disease in the presence of HPV. More than 85% of all cervical cancers have shown evidence of the presence of HPV sequences.^5,6

There are over 80 molecular types of HPV identified. High risk types that are considered oncogenic on the molecular level include 16, 18, 31, 35, 39, 45, 51, 52, 54, 56, 58, and 68 and have been detected in intraepithelial and invasive cancers. Low risk types associated with ASCUS (atypical squamous cells of undetermined significance) and low grade squamous intraepithelial lesions rarely progress to high grade cervical dysplasia. Women at high risk for infection with HPV include those women with initial sexual encounters at a young age and increased number of sexual partners. Condom use does not appear to decrease the rates of transmission.

When the Centers for Disease Control and Prevention (CDC) expanded the surveillance case definition of AIDS in January 1993, invasive cervical cancer was included acknowledging the significance of this malignancy in HIV infected women. Many studies have shown the high prevalence of cervical intraepithelial neoplasm, its rapid progression and inadequate response to standard treatment in HIV infected women compared to the HIV uninfected women.² As a result, the CDC recommends a more aggressive approach to managing cervical disease in HIV infected women. Presently, HIV infected women should have a Pap smear every six months. After two consecutive normal Pap smears these can be done annually. Most providers experienced in the care of HIV infected women continue to screen their patients every six months. Any abnormal Pap smear showing ASCUS (atypical squamous cells of undetermined etiology) and SIL (squamous intraepithelial lesion) must be referred for colposcopy. If the Pap smear shows severe inflammation with reactive squamous cells, a repeat exam should be done in three months.

Patients found to have cervical intraepithelial neoplasia on colposcopy should be considered for standard therapies such as LEEP (loop electrosurgical excision procedure), cryotherapy, cone biopsy, laser treatment, or cold coagulation. All of these procedures have shown suboptimal results in HIV infected women. Recurrence rates have been reported as high as 40-60% and warrant close follow up and sometimes repetitive treatments.

Invasive cervical carcinoma has a more aggressive clinical course in HIV infected women. Immunosuppression not only correlates with possible increases in rates of progression from preneoplastic changes of the cervix to invasive cancer but also resistance to treatment. Treatment for cervical cancer is radiation alone or in conjunction with chemotherapy.

Pregnancy And Perinatal Transmission

In 1996, Florida's AIDS law required every physician and midwife caring for a women who was pregnant to offer HIV testing. As a result many HIV infection have been diagnosed in women during pregnancy and frequently when the women are in the asymptomatic stage of their infection. The early detection of HIV infection in pregnant women is critical for prevention of the transmission of the virus to their newborn.

Several issues need to be considered when caring for the pregnant HIV infected woman such as the effect of the virus and the antiretrovirals on the developing fetus and infant and the possible effect the pregnancy could have on the course of the HIV infection. During normal pregnancy there is a natural decline of CD4+ cell counts with a return to baseline after pregnancy. The association between HIV disease progression and pregnancy may exist but most studies have shown no significant differences when compared to non-pregnant HIV infected women.⁷ Current recommendations for the initiation of antiretrovirals and the goals of therapy should be the same as those for the non-pregnant HIV infected woman.

The AIDS Clinical Trails Group (ACTG protocol 076 showed a reduction in perinatal transmission of HIV infection from 25.5% to 8.3%. The protocol required ZDV to be administered orally after 14 weeks of gestation, continued throughout the pregnancy, administered intravenously during the intrapartum period, and to the newborn during the first six weeks of life. Since zidovudine (ZDV) is the only drug that has been shown to reduce the risk of perinatal HIV transmission, it is recommended that this be given to all pregnant HIV infected women regardless of their immune status, or should be included in a drug regimen prescribed by their provider after counseling. If the women is already on a drug regimen before becoming pregnant all attempts should be made to include ZDV in this regimen.

Recently a study done in Uganda has shown that nevirapine (a non-nucleoside reverse transcriptase inhibitor) given to both the mother and newborn infant can also reduce transmission.⁸ Mothers were given nevirapine as a 20 mg dose orally in labor and 2 mg/kg to the infant within the 72 hours after birth. This was compared to ZDV given as a 600 mg oral dose followed by 300 mg every three hours during labor and 4 mg/kg orally twice daily to the infant for seven days after birth. There was a 48% reduction in HIV transmission in the group given nevirapine compared to the ZDV group. This did not demonstrate better results than the ACTG 076 regimen but may offer a reasonable option for lowering the transmission rate in developing countries where antiretroviral use is limited due to access and cost. A study using nevirapine is being done in the AIDS Clinical Trails Unit in Jacksonville that uses nevirapine in addition to ZDV (ACTG 316).

Low maternal HIV-1 viral loads are associated with lower transmission rates which is obtained with effective antiretroviral treatment.^9,10 Also, the use of cesarean section prior to the onset of labor or rupture of membrane has been shown to lower transmission rates. When considering elective cesarean section in a pregnant women, the risk of increased neonatal morbidity and maternal morbidity and mortality must be considered and discussed with the women during the decision making process. At this time C-section is not considered standard of care for all pregnant women.

Perinatal transmission not only occurs during the antepartum and intrapartum periods, but also the postpartum period through breastfeeding. Breastfeeding has been discouraged in this country according to the treatment guidelines to prevent the possibility of transmission to the infant. But recently a study performed in Malawi showed that uninfected infants at birth had a 10.3% risk of becoming infected when breastfed by the infected mother. The period of highest risk was in the 1 to 5 month period. Recommendations regarding HIV infected women and breastfeeding especially need to weigh the risks of transmission against the known benefits of breastfeeding especially in developing countries.^11,12 In the United States HIV infected women should be counseled not to breastfeed their newborns.

Conclusions

Most women will not become aware of their illness until they develop an AIDS-related illness, receive testing during pregnancy, or lose a partner to an AIDS related illness. Once they are aware of their HIV infection they still may not access care due to social isolation, depression, substance abuse, discrimination, and fear of rejection from family and friends. For most of these women, care for their families takes priority over their own health and for women living in poverty meeting the needs of food and housing for their family are more important. Large cities are now developing programs targeted primarily at caring for the HIV-infected women and their families with improved access to care for the women. Several clinical trials are specifically targeted at women's health care and providing opportunities for us to learn more about this infection in women. Jacksonville is on the cutting edge of this trend. Approximately two years ago, the Rainbow Center for Women, Adolescents, Children and Families started a program specifically addressing the needs of women and families. It is the only program of its kind in the State of Florida and a handful across the nation where HIV infected women and their children receive comprehensive, multi-disciplinary care at the same time and same place.

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