Course Authors
Susan C. Stewart, M.D.
Dr. Stewart reports no commercial conflict of interest.
This activity is made possible by an unrestricted educational grant from 
.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Describe the changing demographics of HIV/AIDS in the U.S. and the emergence of women as group at risk
Describe special features of the infection in women, including viral load, risk factors and unique conditions
Identify modes of vertical transmission (mother to child) of HIV and ways to decrease the risk
List the steps providers should take to help protect women patients from contracting HIV.
The inspiration for this Cyberounds® came from Dr. Adeel Ajwad Butt, who presented an eye-opening lecture, "HIV and Women," in January 2003 at the Annual Meeting of the American Medical Women's Association. Dr. Butt is Assistant Professor, Division of Infectious Diseases, University of Pittsburgh, PA, and Director of HIV-ID Clinics at the VA Pittsburgh Healthcare System. In his presentation, Dr. Butt highlighted the changes in the HIV/AIDS female population in the U.S. and the special problems in women. This Cyberounds® discusses some of the key topics from that lecture and Dr. Butt will be our expert consultant.
In early June of 2001, the Federal Centers for Disease Control marked the 20th anniversary of its first report of AIDS.(1) The report from Los Angeles described five cases of pneumocystis pneumonia (PCP) in young homosexual men who had been in good health previously. CDC experts identified the characteristics of "cellular-immune dysfunction related to a common exposure," and "a disease acquired through sexual contact." As more case reports were received, risk groups were defined: gay men, Haitians, injection drug users. Measurements of cellular immunity showed defects in T-lymphocytes and lymphocyte responsiveness to infections. More associated illnesses and conditions were identified: lymphadenopathy, Kaposi's sarcoma, fungal and parasitic diseases.
In January 1983, the CDC reported on two women with immunodeficiency who were sexual partners of men with AIDS.(2) One was a 37-year-old African American woman who developed oral candidiasis, generalized lymphadenopathy and PCP pneumonia. Blood studies showed lymphopenia and undetectable levels of T-helper cells. Her steady male sexual partner for the previous six years was a man with a history of IV drug abuse who died of AIDS in November of 1982. The second case was a 23-year-old Hispanic woman with generalized lymphadenopathy, lymphopenia and decreased T-helper cells. Her steady sexual partner was a bisexual male who developed AIDS symptoms starting in June of 1982: lymphadenopathy, oral candidiasis, PCP and Kaposi's sarcoma.
These two women are a microcosm of HIV/AIDS in women in the U.S. today: Members of a racial or ethnic minority, heterosexual transmission from a bisexual or injection drug using (IDU) partner. Another large group of women with HIV/AIDS is women who are IDUs themselves.
The Indiscriminate Virus
AIDS entered the United States primarily through the gay male population, now designated "men having sex with men" (MSM) in surveillance reporting. Some thought the disease was exclusive for gay men. It didn't take long to become clear that AIDS was caused by a nondiscriminating virus, first called human lymphotropic virus type III/lymphadenopathy associated virus (HTLVIII/LAV) and then named human immunodeficiency virus type 1 (HIV-1), that would infect and kill anyone if the circumstances were favorable. The other group developing AIDS found on surveillance was injecting drug users (IDUs). A distinction has been made between transmission by drug use between homosexual men -- MSM/IDU-and transmission by drug use in heterosexual men and women-IDU.
Case Definition
Before the virus causing AIDS was identified, a surveillance definition was developed based on the diseases and conditions observed. It included constitutional symptoms; neurologic conditions; opportunistic infections called by viruses, bacteria, fungi and parasites; and cancers. The classification has been revised as new data are analyzed. In 1992, the 1987 definition was expanded to include all HIV-infected persons with less than 200 CD4+ T-lymphocytes or a CD4+ T-lymphocyte percent of total lymphocytes less than 14%, or HIV-infected persons who have been diagnosed with pulmonary tuberculosis, invasive cervical cancer or recurrent pneumonia. This led to a sharp peak in the incidence curve, as shown in Figure 1 below.
Figure 1. Estimated Incidence of AIDS and Deaths of Adults and Adolescents with AIDS*, 1985-2001, United States.
After the virus was identified, infection with HIV was distinguished from AIDS, the critical point at which the virus has destroyed cell-based immunity to the extent that the infected individual is no longer able to control infections caused by viruses, bacteria, fungi and parasites. The initial clinical battle was to control these "opportunistic" infections, but soon specific anti-HIV drugs, the antiretrovirals, were developed that transformed an infection that was a death sentence into a chronic illness. With the arrival of these medicines in the mid-1990s, the AIDS epidemic changed dramatically. The incidence of AIDS decreased as fewer cases of HIV progressed to AIDS, and with AIDS patients living longer, the death rate from AIDS dropped (Figure 1). Finally, the prevalence of AIDS increased because more people with AIDS stayed alive.
Special Note
Before I continue with my discussion of HIV/AIDS in women, I must call your attention to a distinction in the statistics. Now that we have identified the virus causing AIDS, HIV-1, we have statistics on individuals diagnosed with HIV, as distinguished from individuals diagnosed with AIDS. HIV cases change into AIDS cases when the disease progresses. On the other hand, not all AIDS cases are first diagnosed with HIV. So just remember that HIV and AIDS statistics are not about the same groups of people. However, the term, "infected with HIV" refers to HIV and AIDS patients combined.
Women Not Excluded
Although most of the cases reported early in the epidemic were in men, soon AIDS in women was identified. Women contracted the disease primarily by sex with bisexual or injection drug using males or through contaminated needles shared by injection drug users (IDUs). The proportion of AIDS cases among women and adolescent girls (aged >13 years) increased from 8% in 1986 to 26% in 2001 (Figure 2).
Figure 2. Estimated AIDS Incidence in Women and Adolescent Girls.
AIDS cases are concentrated in racial and ethnic minority groups. In 2001, 49% of AIDS cases were African Americans, whereas African Americans make up 12% of the general population.
Figure 3. Reported AIDS Cases and Estimated Population by Race/ethnicity, 2001
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More than 75% of women with AIDS and HIV belong to racial and ethnic minorities, African American or Hispanic, and more than 50% of new infections are in African American women. This concentration is particularly pronounced in the South.
Figure 4. AIDS Incidence Among Women and Adolescent Girls by Region and Race/ethnicity, 2001.
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Initially, intravenous drug use was the most common mode of transmission to women, but, in 1991, heterosexual contact with an infected person became the most common mode. In 2001, 65% of women with AIDS contracted the virus through heterosexual contact, whereas 15% of men reported heterosexual transmission.
Figure 5. Estimated AIDS Incidence Among Adults and Adolescents by Sex and Exposure.
Modes of Heterosexual Transmission
An infected man is twice as likely to transmit HIV to a female partner than the reverse. Anal sex carries a higher risk for infection than vaginal sex. Microtrauma during sex or genital ulcer disease increases the rate of transmission. Genital ulcer disease can increase the risk of transmission 1.5 to 7-fold. Cervical ectopy, the presence of transitional epithelium around the opening of the cervix, is associated with increased risk. Sex during the menstrual period increases risk. The partner is more infective if he has acute HIV infection or more advanced disease with a higher viral load or a lower CD4 count.
Primary HIV Infection
The initial symptoms and signs associated with HIV infection are very much the same in men and women, although they may be more pronounced in women. They are typical of an acute viral illness. They include fever, arthralgia, myalgia, diarrhea, vomiting and lymphadenopathy. Weight loss, sore throat, rash and oral ulcers are also common.
Asymptomatic HIV
Those with HIV infection may remain asymptomatic for up to 10 years until cell-based immunity is destroyed to a critical point. Then the AIDS defining illnesses appear as CD4 cell counts continue to fall in the untreated patients. Treatment is indicated in patients based on the HIV RNA levels (viral load) and CD4 counts. Close to a million people in North America are infected with HIV, and an estimated quarter of these people are not aware that they have the infection. More than one fourth of the 45,000 newly diagnosed cases every year are women. Increasing detection of HIV in women requires close attention to the risk factors for contracting HIV infection and the diagnostic clues that present in the primary care setting.
Women should be asked about high risk behaviors as part of the medical history. Patients are unlikely to volunteer information in the primary care setting. Physicians have to affirmatively ask questions in a nonjudgmental manner about the sexual history. Key risk factors include:
- Multiple sex partners
- A partner with an HIV risk, such as intravenous drug use or bisexual lifestyle
- A sexually transmitted disease
- Trading sex for drugs or money
- Personal use of injection drugs or non-injection drugs, such as crack cocaine or methamphetamines
All women at a higher risk should be offered HIV testing. If the risk factors are not evident and the patient requests to be tested, it is prudent to test them since many women who test positive for HIV report no risk factor. This figure was more than 50% in 1998. On further investigation, the risk is identified as heterosexual contact in more than 75% of these women.(5) This points up the lack of awareness women have for their risk of contracting HIV.
Some illnesses seen in the primary care setting should arouse suspicion of an underlying HIV infection. They can be common infections that recur frequently or occur at an atypical time. One example is herpes zoster in a healthy person under the age of 50 or thrush not related to recent antibiotic use. In women, recurrent vaginal candidiasis, cervical dysplasia, HPV, or cervical cancer itself can be manifestations of underlying HIV.
If the HIV tests are positive, CD4 and viral load tests are used to determine the degree of immune damage and need for treatment. HIV viral load is used to monitor response to therapy, while CD4 counts are used primarily to assess the risk for opportunistic infections and the need for prophylaxis. In primary HIV infection, viral load is generally very high and infected persons are at a high risk to transmit the infection to others. There are some gender specific differences in viral loads, with some studies showing a lower viral load in women than in men when the CD4 counts were the same. At these CD4 levels, the time to AIDS was similar in men and women. When women with the same viral load as men were followed, the risk for AIDS increased to 1.6. If these results are more widely confirmed, treatment guidelines based on viral load may have to be changed for women.(6)
AIDS Defining Illnesses
Initially AIDS was diagnosed by the appearance of unusual infections that could invade a body with waning cellular immunity. Pneumocystis carinii pneumonia (PCP), caused by a parasite, and Kaposi's sarcoma, now known to be caused by a newly identified virus, human herpes virus 8, were some of the first manifestations. The revised classification of 1993, with the inclusion of cervical cancer, increased attention to unique manifestations of HIV in women.
In one series, initial manifestations in women were recurrent candida vaginitis (37%), lymphadenopathy (15%) and bacterial pneumonia (13%). Of the AIDS defining illnesses, Kaposi's sarcoma, seen in 40% of homosexual men and 11% of heterosexual men, was only 1.8% in women. Esophageal candidiasis occurred in 34%, PCP in 20% and mucocutaneous herpes simplex virus in 18% of women with HIV.
Human Papillomavirus Infection and Cervical Cancer
In the revised surveillance definition of AIDS published at the end of 1992, invasive cervical cancer was added to the list of AIDS defining diseases. Higher numbers of HIV-infected women are infected with human papillomavirus (HPV), especially the oncogenic strains. Coinfection with HIV and HPV is associated with more high-grade cervical dysplasia and more rapid progression of dysplasia to cervical cancer. In women with greater degrees of immunosuppression and a higher viral load, the prevalence of dysplasia increases.
The CDC has recommended that HIV infected women have Papanicolau smears six months apart for two screenings. If cytology is normal, annual screening should be done. A study evaluating the effectiveness of this intervention compared with more aggressive regimens using colposcopy found the CDC regimen to be both effective and cost-effective.(7)
HIV and Pregnancy
HIV/AIDS is a disease of young adults, and as the AIDS epidemic spread into the female population in this country, HIV in pregnancy was intensively studied. An estimated 5,000-7,000 HIV-infected women in the U.S. give birth every year. Prior to any interventions, vertical transmission from mother to child occurred in 20-30% of pregnancies and 8-20% of breast fed babies were infected. One-third of transmissions associated with pregnancy were estimated to occur during pregnancy and two-thirds during delivery. Initially, obstetrical management through the course of pregnancy and during delivery were the only factors that could be addressed. Now two other factors have evolved to help produce better outcomes: antiretroviral drugs and technology allowing for measurement of the severity of infection: CD4 lymphocyte count and, more particularly, viral load.
Antiretroviral Therapy and Pregnancy
In 1994 the Pediatric AIDS Clinical Trial Group (PACTG) Protocol 076 showed that using a regimen of zidovudine (ZDV) decreased mother to child transmission of HIV by 66%. The transmission rate in the placebo group was 22.6% compared with 7.6% in the ZDV group. The ZDV regimen consisted of oral ZDV during pregnancy, intravenous ZDV during delivery, and oral ZDV to the infant for six weeks after delivery.(11) Combination or highly active antiretroviral therapy (HAART) given to mothers during pregnancy has reduced transmission further. This treatment became available after 1996. A longitudinal study in the U.S., started in 1990, measured transmission in various treatment groups as follows: no antiretroviral treatment; 20%; ZDV alone 10.4%; combination therapy without protease inhibitors 3.8%; and combination therapy with protease inhibitors 1.2%.(9) Now with increasing use of HAART, women who are already on antiretroviral regimens are becoming pregnant. Studies are underway to determine the safety and adverse effects of the new drugs on mother and fetus.
Viral Load and Vertical Transmission
Higher viral load at baseline and at the time of delivery are both associated with higher rates of transmission. Now the goal of therapy is to reduce viral load to undetectable levels. While the risk of transmission is very low when maternal viral load is undetectable, transmission to the newborn has been reported at all viral load levels. Viral load should not be a determining factor for the use of antiretroviral therapy. The principles of therapy in pregnant women should be similar to the non-pregnant women, except that known teratogenic agents should be avoided. Viral load should be measured at 34-36 weeks to give time for counseling and decision-making about the mode of delivery.(9)
Obstetrical Management
Except in women with very advanced disease, HIV has little effect on pregnancy outcomes and pregnancy has not been shown to affect HIV progression. In managing the pregnancy, any invasive obstetrical procedure, e.g., amniocentesis, is not recommended. STDs should be detected and treated, especially those producing genital ulcers. Exactly how transmission occurs during the course of pregnancy is unknown. A placental infection, chorioamnionitis, could breach the placental barrier and allow infected lymphocytes or virus into the fetal circulation. When detected, the infection should be treated. This is not a common complication and does not account for most of the cases. Transmission may occur by the same mechanism in the absence of placental infection and there may be other ways for the virus to access the fetal circulation. One thing is certain: the amount of infection in the mother is a highly significant factor. As the severity of the maternal infection increases, so does the transmission rate.(8) Intrauterine transmission is significantly decreased by antiretroviral therapy, particularly zidovudine.
Management of Delivery
As noted above, an estimated two-thirds of babies are infected during delivery or because of complications around the time of delivery. Any circumstances that allow the mother's blood or genital secretions to contact the baby increase the risk. Again, severity of maternal infection increases the risk. Other obstetrical measures include avoiding invasive monitoring, artificial rupture of membranes when labor is progressing, and other instrumentation. Premature rupture of the membranes of greater than four hours duration has been shown to increase risk in some but not all studies. Initially, elective cesarean section was offered to avoid the potential traumas associated with vaginal delivery. It has been shown to decrease transmission by 50 to 75%. On the other hand, non-elective cesarean section, done after the onset of labor and rupture of the membranes, does not significantly decrease transmission compared to vaginal delivery, and has twice the complication rate.(9)
The introduction of antiretrovirals and the ability to measure viral load have made pregnancy management more complicated, but have allowed a finer tuning of delivery decisions to decrease transmission and avoid maternal and fetal complications. Women receiving antiretrovirals who have undetectable viral loads and deliver vaginally have as low a transmission rate as women on zidovudine (ZDV) who have elective C-section. C-section would not be expected to lower transmission further. Currently, the American College of Obstetricians and Gynecologists recommend elective cesarean section at 38 weeks for women with HIV RNA levels of more than 1000 copies/ml at the time of delivery.(9),(10)
HIV and Breast Feeding
HIV is present in breast milk and is responsible for an additional 8-20% of perinatal HIV infections. This is a particular problem in developing countries or resource poor areas, where formula feeding is unavailable or too costly. The protective effects of breast milk for infants are especially important in developing countries because of the higher risks of neonatal infectious diseases and the risk of malnutrition.
In the U.S., HIV positive women should be counseled about the risk of transmission associated with breastfeeding and advised not to breastfeed.
Public Health Considerations and HIV/AIDS in Pregnancy
Shortly after the PACTG 076 results were published in 1994, a U.S. Public Health Service task force issued recommendations for the use of ZDV for reduction of perinatal transmission of HIV. The following year in July 1995, USPHS issued its recommendations for universal prenatal HIV counseling and HIV-1 testing with consent for all pregnant women in the United States. This meant that all pregnant women, regardless of age, ethnicity, race or socioeconomic status, were to be counseled about the risks of HIV in pregnancy and advised to have an HIV test. There has been a high compliance rate with these recommendations by physicians and patients. A report from the Michigan Department of Health reported a decrease in perinatally HIV-infected children from 19% to 3% from 1993 to 2000. Michigan health analysts observed that HIV positive women had more STDs, alcohol and illegal drug use, and a higher rate of no prenatal care, 10% vs. 1% in women not infected with HIV. Conversely, women with no prenatal care had a lower rate of HIV testing, 58% vs. 94% in women with one or more prenatal visits.(12) Increasing access to prenatal care and providing treatment for drug and alcohol use are both public health priorities for further decreasing perinatal HIV infection.
HIV/AIDS Prevention in Women
Practitioners must not overlook clinical clues to HIV infection, such as recurrent vaginal candidiasis, herpes simplex virus or an STD. Healthcare providers must take a thorough history covering all risks, and offer testing when risks are detected. Never miss an opportunity to counsel about safe sex and help women with drug and alcohol problems get treatment.
Second, we should be constantly giving preventive messages about HIV/AIDS. We owe it to our patients to continually question, educate and sensitize them about risk. Historically, in surveys of AIDS cases, a large portion of women has been reported without risk information. With investigation, the majority were determined to have had heterosexual transmission and most of the remainder, injection drug use. Women should attempt to know the HIV status of their partner. These data show that women were simply unaware of their risk and were not taking precautions against heterosexual exposure to HIV virus. Condoms should be used at all times until partner status is confirmed. Oral sex is NOT safe and protection should be used in the same circumstances as vaginal or anal sex. There is no such thing as an antiretroviral "morning after" pill to protect against HIV after risky sexual behavior.
There is an ominous trend both in AIDS cases and HIV diagnoses among adolescents and young adults in the U.S. The sex ratio is moving toward 1:1. For 2001 data showed that of AIDS cases diagnosed in 13-19 year-olds, 48% were female; in 20-24 year-olds, 41% were women; and in age 25 and over, 25% were women (see Figure 6).
Figure 6. AIDS in Adolescents and Adults By Sex and Age at Diagnosis 2001.
In HIV diagnoses in 13-19 year-olds, 56% were female; ages 20-24, 40% were women; and age 25 and over, 30% were women (Figure 7).
Figure 7. HIV in Adolescents and Adults By Sex and Age at Diagnosis 2001.
In the two younger groups, 66% contracted AIDS through heterosexual contact. Three quarters of these young women are African-American or Hispanic. The trends in these age groups are a harbinger of the continuing epidemic. Risky sexual behaviors and drug use continue to occur in adolescents and young adults, and need to be addressed by comprehensive educational programs.
Summary
Knowledge about the progression of HIV/AIDS into the female population in the U.S. has been slow to sink into public consciousness. The proportion of women diagnosed with HIV each year in the U.S. is increasing, now 26% overall. More than half of adolescents newly diagnosed with HIV infection are female. For women, heterosexual transmission is the major mode of acquiring the infection, followed by injection drug use. Use of antiretroviral drugs and viral load measurements can dramatically decrease mother to child transmission of the HIV virus. As practitioners, we need to think of HIV infection in patients with histories or conditions indicative of HIV or AIDS, and we should ensure that they receive appropriate and timely treatment. Finally, we should affirmatively educate and counsel female patients, particularly the young, to be knowledgeable and protect themselves against HIV infection.
Web Site Resources
The CDC Divisions of HIV/AIDS Prevention. Choose health topics a-z, then AIDS/HIV. This site has comprehensive information on the U.S. AIDS epidemic: statistics, information, prevention, educational tools.
Figures: All figures in this conference were taken from the CDC public domain slide sets available on the CDC HIV/AIDS website. They are available to download for further study or educational presentations.