Treatment strategies for women examined at physicians' forum
Women and HIV
The media is still "not with it" when reporting changes in AIDS death statistics, said Dr. Alexandra Levine at the beginning of a Feb. 19 lecture on the management of HIV disease in women, part of a meeting of the L.A. Physicians AIDS Forum.
Levine, a principal investigator in the Women's Interagency HIV Study (WIHS) and medical director of the Norris Cancer Hospital in L.A., went on to present a slide that illuminated the increasing incidence of AIDS among women (who represent 42 percent of all AIDS cases worldwide). In the U.S. alone, the percentage of women who make up total AIDS cases has nearly tripled from 7 percent in 1985 to 20 percent in 1996. While the majority of these women are diagnosed between the ages of 22 and 45, a number of them (3 percent) are over the age of 60.
Social issues affect health care
Certainly, HIV infection is not easy for anyone, but Levine has observed that women are very likely to experience a sense of profound isolation as a result of knowing that they are HIV-positive.
She cites a finding in the WIHS study that a significant number of the more than 2,000 positive participating women state that they have never met, or spoken to, another woman living with HIV. Many refuse to allow phone calls or mailings that pertain to their health status. Women infected with HIV are effectively more than a decade behind men in the development and availability of appropriate social support services.
There does not appear to be any difference in survival among HIV-infected men and women receiving identical medical care. Women may actually tend to live slightly longer than men, as is the case with many other diseases. Still, psychological and social barriers to accessing quality care exist.
One of the primary differences in the occurrence of opportunistic infections is Kaposi's sarcoma. Women do get KS, although far less frequently than men. Once again referring to the WIHS study, Levine revealed that 18 percent of the participants test positive for HHV-8 (by PCR), the virus now known to cause KS. The number of women who actually manifest KS remains to be seen over the course of the study, which is now in its fifth year.
Manifestations in women
In a study of 200 HIV-infected women in the U.S., the most common reason women first sought medical attention was recurrent vaginal yeast infection (37 percent). Enlarged lymph nodes was the next most common initial manifestation (15 percent), followed by bacterial pneumonia (13 percent).
Cervical cancer was added to the list of AIDS-defining conditions in 1993. Like KS, it is a malignancy that is associated with a viral infection -- in this case, human papilloma virus (HPV). HPV, which also causes genital and anal warts, is sexually transmitted and not limited to HIV-infected individuals (a recent article in the New England Journal of Medicine reports that 60 percent of college women in the U.S. are HPV-infected).
The incidence of HPV infection tends to decrease in older women because the virus can actually be cleared in healthy individuals. In the immunocompromised, however, HPV can reactivate.
There are many sub-types of HPV with types 16, 18, 45, 56, 31 and 33 tending to be associated with the development of cancer. Fifty-eight percent of the positive women and 26 percent of the negative controls in the WHIS study are HPV-infected. In the HIV-positive group, 40 percent are infected with multiple types and 24 percent with more than three types. In the women with CD4 counts below 200, 70 percent are also infected with HPV, probably due to reactivation of the virus.
A Pap smear is typically used to detect cellular changes that occur in the cervix that may indicate a risk of developing cancer. HIV-positive women have a 30-to-40 percent chance of having an abnormal Pap smear after testing positive. However, a colposcopy examination can more readily detect these changes. During a colposcopic exam the practitioner can place a solution on the cervix that causes areas infected with HPV to become lighter than surrounding areas. At this point, a biopsy (the removal of a small amount of tissue) can be performed and analyzed.
It's important to know that 17 percent of HIV-positive women are diagnosed with high-grade SIL (a pre-cancerous condition) even though their Pap smear is normal. This may indicate that colposcopy and biopsy should be incorporated into a standard of care for HIV-infected women.
Treatment for SIL and other pre-cancerous conditions are not as effective in HIV-positive women. Only 10 percent of negative women will have a recurrence of the condition, as compared to 40-to-60 percent of positive women. Vigilant monitoring is required.
Invasive cervical cancer is usually more serious in women who are HIV-positive than it is in HIV-negative women. As many as 100 percent of positive women will have a recurrence of their cancer with in two months following definitive treatment. The statitsic that survival after recurrence averages nine months appeared to stun medical professionals in the audience at the presentation.
Sex and drugs
Many HIV-positive women express concern about the lack of hard data on the safety and efficacy of antiretroviral drugs in women.
Weight and hormonal differences between men and women is usually the point of focus. Zerit, Videx and several other drugs are dosed based on body weight or volume. Levine believes that dosing of other antiretrovirals for women may be refined in the future.
While extensive research has not been conducted in this area, it appears that, with some minor phamacokinetic (drug metabolism and clearance) variances, HIV medications are equally effective in men and women. Toxicities (side effects) in women who take protease inhibitors tend more toward nausea and vomiting while men are more likely to experience diarrhea. The redistribution of body fat known as lipodystrophy ("buffalo hump," "protease paunch") is occurring in men and women in what Levine views as equal frequency.
Women who are taking hormonal contraceptives (the pill, Depo-Provera, Norplant) must be aware that protease inhibitors will significantly lower blood levels of those drugs. Effectiveness is reduced and pregnancy may occur if additional precautions, such as a diaphragm or condom, are not used. Protease inhibitors may also interact with hormone replacement therapies used by menopausal women.
Abnormal menstrual cycles
Many HIV-positive women report changes in their menstrual cycle, including longer, shorter, heavier, irregular or painful periods. This is true of the women in the WIHS study, as well. Surprisingly, no difference was seen between HIV-positive women and HIV-negative women when it came to this phenomenon. As Levine said, "Abnormal periods are normal."
Something that is particular to the HIV-positive woman, however, is the absence of any menstrual cycle whatsoever. This condition, called amenorrhea, occurs at a younger age in HIV-positive women than would be expected in the general population. Amenorrhea is three times more likely to occur in HIV-positive women.
Levine explained that this was originally thought by many to be premature menopause in which ovarian function wanes and eventually ceases. The role of HIV in this theory was not understood.
Based on the measurement of FSH (follicle stimulating hormone) it is now thought that amenorrhea is the result of central pituitary failure. In true menopause, the pituitary gland (located in the base of the brain) would work to compensate for that lack of ovarian function by producing FSH. The levels of FSH detected in HIV-positive women experiencing amenorrhea do not indicate true menopause.
HIV and pregnancy
Despite data on the lack of toxicity of many anti-HIV medications to the fetus, Levine asserts that medical management of the woman patient should be the paramount concern of physicians and combination therapy utilized if indicated. Because of the demonstrated efficacy of AZT in reducing the likelihood of perinatal transmission, women who remain on combination therapy throughout their entire pregnancies should consider adding that drug into their regimen until delivery.
Medications fall into four risk categories when considering damage to a developing fetus. "A" (no risk), "B" (no risk in humans), "C"(risk not ruled out) and "D" (high risk). Drugs for HIV are in the "B" and "C" categories.
For pregnant women who choose not to take medication during pregnancy, even short-term treatment with AZT may significantly reduce the incidence of perinatal transmission as demonstrated in controversial placebo-controlled studies conducted in developing nations. Levine also stated that exposure to AZT intravenously during labor may be a highly critical point of intervention for women who have taken no medication at all.
Following Levine's presentation, a woman living with AIDS reviewed her nine-year history of antiretroviral treatment and discussed her relationship with medical providers. Hearing the patient's perspective highlighted for the audience the importance of individualizing treatment strategies. Women and men with HIV may not differ clinically as much as one would expect, but no two patients are alike.
This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.