Research Findings from the Women's Interagency HIV Study

Following are summaries of some of the research findings on HIV positive women over the last few years from WIHS (Women's Interagency HIV Study). This study was started in 1994 and follows women with HIV and women at high risk of HIV every six months. See other stories in this section for definitions of words in italic letters.

Cervix Woes

There is conflicting data about the relationship between vitamin A deficiency and cervical cancer. A look at HIV positive women found that vitamin A deficiency was associated with abnormal Pap smears (the first step towards cervical cancer). It didn't matter if the women had low T-cells or HPV (human papilloma virus), both of which are more likely to be present in positive women with abnormal Pap smears. The vitamin deficiency by itself was an independent risk factor. It was also related to injection drug use and low income. (1999)

"Even in the face of HIV infection, relatively immunocompetent women can eliminate squamous cervical lesions," researchers reported. The likelihood of abnormal cytology [cell findings] among women with HIV was high. Two out of three positive women had abnormal test results, compared to one out of three negative women. However, the so-called "cumulative risk" (over time) of HSIL (high-grade squamous intraepithelial lesions) and cancer was not high. (2000)

Comparing a group of 2,000 positive women with 500 HIV negative women, researchers found that 38% of the positive women showed abnormalities in their Pap smear vs. 16% of negative women. Positive women were also twice as likely to have high-grade (significant) abnormalities (2.3% vs. 1.3%). The researchers reported that while infection with HPV most predicts Pap smear abnormalities, other predictors included low T-cells, younger age (under 30), and ever having had tuberculosis. (1997)

In a different report, the same group of researchers noted that positive women were twice as likely to have HPV (58% vs. 27% of the negative women). Since then, four HPV types have been most strongly associated with leading to cervical cancer. One group of researchers found that women with HIV and HPV who developed abnormal cervical cells had equal numbers of low-risk and high-risk HPV types. In contrast, 80% of the negative women with cervical abnormalities had the high-risk strains. Therefore, even the "innocent" strains of HPV can cause problems for positive women. (1997)

But there is really good news for women in the HAART era! For women with Pap smear abnormalities, those who began on highly active antiretroviral therapy (generally a triple combination of HIV drugs) were less likely to continue having abnormalities. They were also less likely to have HPV even if they had it before going on medication, no matter what their viral load or T-cell count. "[HAART] appears to have a beneficial effect on coincident HPV infection and disease," researchers concluded. (2001)

"Preliminary evidence suggests that immune reconstitution following HAART impacts HPV-associated disease," researchers noted. They found that women on HAART were more likely to have a lack of progression in abnormal cervical cells. They even had regression of disease. (2000) HAART use significantly reversed cervical abnormalities to normal or to less severe. (2001)

Pap smears alone missed precancerous changes in a third of positive women tested. Even using a higher level of examination, a colposcopy, still missed precancerous abnormalities in a third of positive women. Comparing these women's findings of abnormalities further with a biopsy, in which a piece of cervical tissue is taken off and examined, is what identified the seriousness of their condition. "Liberal use of biopsy is essential for proper management of women with abnormal smears," researchers reported. (See also "Controversies," below.)

Deaths

The Centers for Disease Control and Prevention (CDC) and WIHS both reported findings that active drug users who were HIV positive had a substantial rate of death from non-HIV causes. The CDC in 2000 reported that in one group, many of the women were not using strong combination HIV drugs available to them. Only one out of four of the women with less than 200 T-cells were on HAART. In this group, a third of the deaths not related to HIV resulted from illicit drug use, and the CDC cited the need for hepatitis vaccinations and better drug treatment options.

WIHS reported similar findings in 1999. "A substantial minority" (one out of five of the deaths with known cause) were due to non-AIDS related deaths. These included deaths from liver failure, murder, suicide, and overdose on illicit drugs. "While the number of deaths from AIDS has significantly decreased, the number of deaths from non-AIDS causes has remained constant, and in the HAART period make up a higher proportion of deaths among women with HIV. These causes of death need to be addressed if we are to continue to reduce mortality," WIHS concluded.

Thrush

Researchers looked at the effectiveness of weekly intravaginal application of Lactobacillus acidophilus gelatin capsules or clotrimazole 100 mg tablets. There was a significantly longer time to the first episode of vaginal thrush with clotrimazole, but not with the acidophilus. Still, they reported that, "Both interventions reduced the number of episodes by half. Vaginal yeast infections can be prevented with local therapy and prophylaxis [prevention] should be offered to HIV infected women as part of routine primary care." Elsewhere, a gynecologist, and HIV specialist, reported that in her clinical experience, she had found that boric acid suppositories prepared by pharmacists had cleared some yeast infections. (2000)

Period Woes

WIHS and other investigators reported on menstrual abnormalities in women with HIV compared to those without HIV. After adjustment for demographic differences (age, ethnicity, etc.), body mass index and substance abuse, it was found that being HIV positive increased the odds of having both a very short menstrual cycle and a very long menstrual cycle. Being HIV positive did not increase the odds of having a moderately long cycle, or affect average cycle length and variability. Although HIV may slightly increase the possibility of very short cycles, HIV serostatus has very little effect on amenorrhea (the absence or stopping of menstruation), menstrual length or variability. Among HIV positive women, higher viral loads and lower CD4 T-cell counts were associated with increased cycle variability. (2000)

Lung Woes

Researchers found twice the rate of lung infection in positive women as in high-risk negative women. Eighty-five percent of all the women smoked cigarettes and 50% used injection drugs. (2000)

Anemia

WIHS reported that women who used HAART for at least 18 months had a reduced risk of developing anemia. There was also resolution of anemia for those who had it before starting meds and increased their T-cells or those who used HAART for more than 18 months. However, women who continued to use Retrovir (AZT), which can cause anemia, did not see an improvement. The researchers noted that, "Anemia is an independent risk factor for decreased survival in HIV positive women." It is common in positive women, more so with higher viral load levels (HIV in the blood), lower T-cells, clinical AIDS, Retrovir use, low mean corpuscular volume (MCV, the size of their red blood cells), and African American ethnicity. (2000)

Happiness

"Feeling bad lately"? You might if you believe that, "There is nothing you can do [about getting sick] if you don't have good health care." On the other hand, those women who believed "a person can have HIV but never get sick" reported having more "excellent health" and "feeling happy."

Women who said their health wasn't so good were more likely to agree with the statement, "It is not worth following a difficult health plan/regimen." The women who disagreed were more likely to say that they did enjoy good health. (1999)

Depression

Depression leads to lower T-cells and greater risk of death in positive women. The findings add to knowledge that depression is a risk factor for death for positive people, male and female. (2001)

Transmission

The presence of STDs (sexually transmitted disease) is known to increase the risk of becoming infected with HIV. A study with Kenya women found that the presence of vaginal thrush and trichomonis lead to greater shedding of HIV in their vaginal secretions, which may increase the risk of transmission to their partner. (2001)

Another, very tiny, study found that cervical inflammation and genital ulcers also increased HIV shedding. (2001)

Diabetes

Although new cases of diabetes were rare, they happened twice as often in women using a protease inhibitor (3% vs. 1.3%). Even improvements in viral load did not help this trend. Nevertheless, these was an even greater risk of developing diabetes for those women on a protease inhibitor whose viral load did not decrease. (1999)

Breast Cancer

Researchers reported unusual cases of breast cancer seen in positive women, at an early age. The report needs follow-up research to determine how significant this finding may be. (1997)

Childhood Abuse and Domestic Violence

A WIHS study of more than 2,000 positive women and 500 negative women found that two-thirds of the women had a history of domestic abuse, including physical, emotional or sexual abuse. The study also noted that, "A history of childhood abuse may identify women at increased risk for sexual and physical victimization as adults. Further, childhood abuse is related to increased participation in behaviors identified as high risk for HIV infection." (1997)

Taken primarily from the WIHS website. Visit www.statepi.jhsph.edu/wihs/index.html.

Severe Inflammation Evaluate for infection; repeat Pap preferably within 2-3 months. Atypical (not typical) or ASCUS Follow-up Pap without colposcopy (may even do colposcopy with one Pap with ASCUS); repeat every 4-6 months for 2 years until three exams are negative; if two ASCUS findings in a row, do a colposcopy. LSIL Colposcopy with or without a biopsy. HSIL and Carcinoma In Situ Colposcopy with biopsy. Invasive Carcinoma (Cancer) Colposcopy with biopsy if there is a lesion, or conization; treat as appropriate with surgery or radiation. Taken from the 2000-2001 Medical Management of HIV Infection by Drs. John G. Bartlett and Joel E. Gallant. The authors also note, "Newer methods of cytologic evaluation [looking at cells] using liquid-based collection and thin-layer processing may enhance sensitivity but have not yet been evaluated in HIV infected women."

Treatments These treatments require local anesthesia and can be done as an outpatient procedure (except the hysterectomy). Choice of treatment depends on the location and size of the abnormal cervical tissue and the extent of the disease being treated, among other factors. Chemical treatments: use of trichloroacetic acid (TCA); Podophyllin; Podofilox; 5-fluorouracil cream (5-FU); interferon alpha; and Aldara (imiquimod). These treatments are toxic. Colposcopy: Examining tissue with a tiny microscope. Biopsy: Taking a tissue sample. Can cause some bleeding, cramping and, rarely, infection. Cone biopsy (also called conization): Cutting off a section of precancerous or cancerous tissue, done in the shape of a cone. General anesthesia may be used. In addition to being a treatment, this procedure can also show whether cancer has become invasive. This procedure can be done with a knife or with an electrical loop (see LEEP). LEEP (Loop Electrical Excision Procedure): a biopsy done with an electric wire loop to slice off a thin, round piece of tissue; can also use LEEP to perform a conization. D and C (dilation and curettage): Stretching the cervical opening and using a curette (a small, spoon-shaped tool) to collect tissue samples from the uterus. General anesthesia may be used. Cryotherapy (freezing): destroys tissue, including warts, with an instrument called a cryophobe, the tip of which has been cooled by carbon dioxide or nitrous oxide gas. No longer recommended for HIV positive women. Cauterization (burning, also called diathermy): destroys tissue, including warts, by using a heated instrument, an electric current, or a caustic substance. Laser surgery: cutting with a very thin beam of light. Hysterectomy: removal of the uterus, with or without the ovaries. Causes periods to stop. Controversies Doctors swear by the Pap smear as the best method of detecting cancer early. Just get one on schedule like you're supposed to. But problems with the test have made media horror stories, showing women dying unnecessarily from cancer that wasn't found early. Problems include negligent labs that try to read too many smears a day and therefore whiz by dangerous cells. Now there are new methods that can improve on the Pap smear. But, of course, doctors are showing their conservative stripes with the old "it isn't proven" line. The HIV docs, in turn, are saying, "it isn't proven to help women with HIV." A Pap with speculoscopy is a standard Pap smear followed by a vinegar wash. Then a chemical light on a microscope is used to look for abnormal cells. It's not much more expensive than the Pap, but the difference is not paid by insurance. It is available at many Planned Parenthood clinics. It's as sensitive (as good at catching abnormalities) as a colposcopy with biopsy. That's an improvement over the standard Pap, but abnormal findings from a speculoscopy will still need to be followed up by a colposcopy with biopsy for confirmation. There's also a different type of Pap smear, in which the handling of the cells differs. Instead of being smeared right onto a slide, the cells are first put into a tube with liquid that helps sort out mucus and other contaminants, and avoids clumping. The sample is then put on a slide as usual. These Pap tests are called "ThinPrep." It allows for HPV testing, as well, to see if you have strains that are highly associated with cancer. There are also computerized readings of slides that may pick up abnormalities not seen by cytologists (the people reading the slides). The ThinPrep people say a computer program can't pick up abnormalities that aren't there because of a bad sample collection. The speculoscopy people say a sample collection can't pick up the abnormalities that haven't shed, but which the speculoscopy light can see.