Alarming New Findings Suggest Treatment Recommendations Must Be Changed for Women

Researchers from Johns Hopkins and the National Institute of Allergy and Infectious Disease report that HIV-positive women may have a higher risk of progressing to AIDS than HIV-infected men with the same viral load.

Led by Dr. Farzadegan, a team of researchers studied 812 specimens from 650 HIV-infected, injection drug users participating in a continuous study at a Baltimore clinic.

HIV viral load was assessed during an initial (base-line) visit, and again on follow-up visits 3 years later. Findings from the decade-long study of HIV-infected injection drug users indicate that HIV-positive women who have used injection drugs may need a different schedule for anti-AIDS therapy from current practice.

The data, published in the November 7 issue of The Lancet, show that, among study subjects who developed AIDS, levels of HIV were significantly lower in the women than in the men.

The study was designed to analyze the relationship between gender using three different methods of measuring viral load. HIV viral loads were tested with branched-chain DNA, reverse-transcriptase PCR, and quantitative microculture. The study results demonstrated significantly lower median viral load measurements in women by all three methods. According to these assessments, the women in this study who progressed to AIDS had viral loads measuring 38% to 65% less than those in the men.

When women were compared to men, their median viral load was 3365 vs. 8907 by bDNA; 45,416 vs. 93,130 by PCR; and 5 vs. 8 infectious units per million peripheral blood cells by quantitative microculture.

Simply Put

Simply put, the scientists found that positive women who inject drugs can develop AIDS with less virus than positive men who inject drugs. And visa-versa, it takes more virus for men to develop AIDS than women, in fact, it takes twice as much virus.

In terms of how fast someone would progress: They say it is about the same amount of time for men and women.

These findings indicate that women who use injection drugs develop the disease with as little as half the viral load of men who use injection drugs. In addition, women with the same viral load as men had a greater risk of progressing to AIDS.

These findings remain statistically significant even when adjusted for CD4 cell count, race, and recent drug use. "Proportional-hazards models show that women with the same viral load as men had a 1.6-fold higher risk of AIDS (95% CI 1.1-2.32); or, equivalently, that women with half the viral load of men had a similar time to AIDS as men," wrote Johns Hopkins researcher Homayoon Farzadegan and colleagues.

"These findings could be an important first step in understanding the course of HIV/AIDS in each gender," said Dr. Alan I. Leshner, Director of the National Institute on Drug Abuse (NIDA). Continued research needs to answer whether this HIV progression holds for a non drug-using population as well.

Explanation for the lower viral loads in women in the study remains elusive, with researchers considering several alternatives: different HIV-1 dynamics in men and women, and/or gender-linked behavioral differences that might influence viral load, and hormonal differences. Still, exactly why the observed phenomenon occurs is unexplained.

The authors warned that their findings should not be interpreted to mean that women have a shorter time to AIDS after HIV infection. They instead stress the interpretation that the relationship between viral load and AIDS is different for men and women.

While further studies are needed, the authors suggest that the initiation of anti-HIV therapy at a lower viral threshold may be justified in women.

Further, it can be concluded that if a given viral load measurement differs in clinical significance in women, treatment strategies using these measurements may have to be optimized separately from those of men.

Farzadegan et al. noted that current U.S. Public Health Service (PHS) guidelines recommend beginning antiretroviral therapy for patients with viral loads of 10,000 copies/mL when CD4 counts are >500 cells/(micro)L.

Standard of Care

The PHS guidelines are used to set a "standard of care" which physicians depend upon to help them determine what the best treatment plan is for their patients.

These guidelines, however, were developed on data collected in studies of men. "A downward revision of the viral-load threshold for women by as much as half (5000 copies/mL) might be prudent," they warned. "The possibility that women -- according to current guidelines -- will be under-treated on a population level must be carefully considered."

Community Concern

Many women are concerned that the Baltimore findings are not unique. In fact, some researchers involved with WIHS (The Women's Interagency HIV Study -- a study looking at disease progression in women) as well as other researchers at medical centers in Texas and Ontario, have collected similar data. They, however have not released any conclusions from their findings. Similar studies are being conducted in the UK and Italy.

Changes

The Federal Guidelines Committee will not consider changes in "The Guidelines for the Use of Antiretroviral Agents in HIV-infected Adults and Adolescents" for treatment of HIV infection.

All the guidelines for treatment and care of the disease are based on research done exclusively on disease progression in men.

The Federal Guidelines Committee is also, not surprisingly, composed of a majority of men. The committee did however, discuss this issue amongst themselves.

Pass On the Info

A member of the Guidelines Committee explains:

"Please pass on the information that the Federal Guidelines Committee does NOT recommend changing the treatment guidelines based on this data. While the group did not question the data, it concluded that it was collected in a relatively narrow subset of women with HIV (primarily IV drug users) and may or may not be applicable to others.

"More importantly, the committee concluded that the difference being reported is still within the normal error variance of the test and therefore does not warrant making changes.

Early Stage of Disease

"If correct, this data only impacts on women at the earliest stages of disease, where the current guidelines are the least compelling about putting people on treatment. Urging every woman with 5000 copies of virus to get on treatment, when the risk rate of progression is still very low even with the new data, could be argued to do as much harm as good.

"Moreover, discussion of this issue may be sending the wrong message, one that implies that the Guidelines urges making treatment decisions solely based on viral load. It does not. The decision to treat must still be based on a combination of factors, including viral load, CD4, time from infection, clinical condition, and patient readiness to start."

WA Position

Women Alive holds fast to our position as published in the Women Alive Newsletter -- issue Summer-1997:

On behalf of the Board of Directors, Volunteers, and Staff of Women Alive, we wish to provide public comment on subject document: it must be acknowledged that there are currently minimal data available on either the natural history of HIV infected women or the pharmacokinetics and safety of antiretroviral agents in women. The physician and the woman patient should be fully aware that the guidelines for therapy for HIV infection are based on theoretical considerations from research done almost exclusively on men.

Uncertainties

Acknowledgments must be made of uncertainties including female-tested antiretroviral efficacy, dosages and toxicities. In the absence of clinical trial data, drug choices will need to be individualized based on discussion with the female patient and on available data about women from pre-clinical and post drug approval clinical testing of individual drugs and/or combinations of drugs.

Clinical Trials

When possible, female patients requiring and choosing antiretroviral regimens, which include any drugs that have not been studied in statistically significant numbers of women, should be referred for consideration in appropriate clinical trials.

Back to the Women Alive Winter 1998-99 Contents Page.