Published in the Bulletin of Experimental Treatments for AIDS April 1998 issue, by the San Francisco AIDS Foundation.

April 1998 Table of Contents

Main Page

beta@sfaf.org

Selected Highlights on Women and HIV from the 5th Conference on Retroviruses and Opportunistic Infections

Harvey S. Bartnof, MD

Other highlights from the conference appear elsewhere in this issue.

Indinavir Blood Levels Vary at Different Times of Menstrual Cycle

In a provocative study from the State University of New York at Buffalo, researchers demonstrated that blood indinavir concentrations may fluctuate with different phases of the menstrual cycle. Only 6 of 15 women have been tested thus far. The median "area under the curve" concentration (in nanomolar-hours) was 20,200 during the menstruation phase, 34,000 during the follicular phase (after bleeding, before ovulation) and 27,600 during the luteal phase (after ovulation, before bleeding). The statistical significance was not tested or reported, and the ranges of each concentration were rather wide and overlapping when comparing the 3 different time periods. HIV RNA viral loads were also measured, but have not yet been reported. The data should be considered preliminary and specific conclusions are difficult to draw. However, the findings may eventually have wider significance. It is possible that levels of many drugs may vary significantly in women with phases of the menstrual cycle, which correlate with varying levels of female hormones. There are few studies in this area.

Adams J and others. Indinavir pharmacokinetics and menstrual cycle physiology. CROI. Abstract and poster presentation 356.

Abnormal Kidney Function in 38% of Women Taking Indinavir

Researchers from the University of Innsbruck in Austria concluded that abnormal kidney function is more common among women than among men with AIDS who are taking indinavir. The study followed 72 patients for a median of 44 weeks; 21 of participants (29%) were women. Eight of 21 women (38%) developed elevated blood creatinine levels (greater than 1.4 mg/dL) during 2 or more monthly visits. The abnormality developed in only 5 of 51 men (10%) in the study. Abnormal kidney function was also significantly more likely to occur in association with each of the following: white blood cells in the urine without bacteria (sterile pyuria), red blood cells in the urine, and documented kidney stones, with the associated symptoms of back/groin pain. White cells in the urine preceded the increase in blood creatinine by 5-24 weeks. All 8 women had significant decreases in HIV RNA viral loads in addition to mild to severe hair loss.

Kidney biopsies showed normal glomeruli (the filtering part of the kidney) with abnormal inflammation and fibrosis. Increasing daily fluid intake to greater than 3 liters (three quarters of a gallon) daily had some beneficial effects. Within 2 months after stopping indinavir, creatinine levels normalized and sterile pyuria resolved. Women with pre-existing kidney abnormalities were not included in the study, but the authors noted that "underlying risk factors other than indinavir might have played a part in the nephrotoxicity [kidney toxicity]..." While additional studies would be helpful, women (and men) who are taking indinavir should undergo regular urine testing. Those who develop pyuria may need to be monitored more closely for the development of both kidney stones and increased creatinine levels. It may also be prudent for them to increase their daily fluid intake.

Sarcletti M and others. Increased risk of indinavir nephropathy in women. CROI. Abstract 418.

Abnormal Pap Smears in Women with High Viral Load

Researchers from the University of Rochester found a high statistical correlation between HIV RNA viral load in blood and abnormal Pap smears of the uterine cervix. In a cross-sectional study of 93 HIV positive women, 51% of women with a blood HIV viral load greater than 10,000 copies/mL had abnormal Pap smears, compared with only 22% of those women with blood HIV viral loads less than 10,000 copies/mL.

In addition, 49% of women with an HIV viral load greater than 10,000 copies/mL had cervical infection with oncogenic (cancer-causing) types of human papillomavirus (HPV), compared with only 22% of women with a blood HIV viral load less than 10,000 copies/mL. Forty-seven percent had positive HPV DNA tests from the cervix. HPV infection was not related to either blood CD4 count, the use of cigarettes or the use of oral contraceptive pills. A multivariate analysis (done to tease out co-factors) was not done. The authors concluded that more aggressive gynecological monitoring was indicated in HIV positive women with blood plasma HIV RNA viral loads greater than 10,000 copies/mL.

Luque A and others. Prediction of cervical human papillomavirus and disease by magnitude of HIV-1 plasma RNA level. CROI. Abstract and oral presentation 258.

High HIV Viral Load Increases Death Risk for Women

The Women's Interagency HIV Study (WIHS) of 2,058 HIV positive and 567 HIV negative women has confirmed what has been previously shown in the Multicenter AIDS Cohort Study (MACS) of gay/bisexual men (see BETA June 1996, pages 9-10, 41-42). A higher baseline HIV RNA plasma viral load increases the risk of subsequent death. The prospective study followed women from 5 U.S. cities for a median of 22.8 months. In a multivariate analysis, researchers found that the relative risk of death with each increasing quartile of viral load (in copies/mL) was as follows (when compared with a baseline viral load of less than 4,000): 2.8 (viral load 4,000-20,000); 2.0 (viral load 20,001-100,000); 3.79 (viral load 100,001-500,000); and 7.1 (viral load 500,001 or greater). Even though there was a small decreased risk when comparing the second lowest with the lowest quartiles, the overall increasing risk was statistically significant.

Regarding CD4 cells, when compared with a baseline count of 500 cells/mm³ or higher, the relative risk of death was 1.01 (200-499 cells/mm³); 2.9 (50-199 cells/mm³); and 8.1 (less than 50 cells/mm³). Use of both measurements provided even more information. Women with a baseline HIV viral load of 500,000 copies/mL or higher and a CD4 count less than 50 cells/mm³ had an 18 month mortality rate of 72%. The mortality rate for those with a baseline viral load less than 20,000 copies/mL and a CD4 count of 200 cells/mm³ or greater was only 3%. This represents a relative increased death risk of over 35-fold for the women with the poorer baseline measurements. There were no significant survival correlates with race/ethnicity or HIV transmission route. There was a trend toward shorter survival in participants who were older at the time of HIV transmission, a finding that has been reported in the past for both gay/bisexual men and hemophiliac men.

There were several limitations to the study. Follow-up time was much shorter in this report than in the MACS study. The time frame was 1994-1995, when there was possible confounding due to anti-HIV therapies (the baseline time period from the MACS was 1985). Concomitant anti-HIV therapy taken by the women was not mentioned in the abstract.

Anastos K and others. Quantitative HIV-1 RNA and other factors associated with survival in the Women's Interagency Study (WIHS). CROI. Abstract 207.

Only 30% of ddI Taken by Pregnant Women Crosses Placenta

In a Phase I study of 12 pregnant women with HIV/AIDS, only a fraction of ddI was found to cross the placenta, according to researchers of the AIDS Clinical Trials Group (ACTG) study 249. Women were enrolled after 26 weeks of pregnancy and took a standard dose of ddI every 12 hours. Concomitant AZT use was encouraged. Intravenous ddI was given during labor and delivery. Concentrations of ddI in placental cord blood at delivery was found to be 30-35% of the level in the mothers blood during labor. No ddI toxicities were noted in the mothers. No toxicities, birth defects or physical abnormalities were noted in the newborns up to age 3 months. Placental transfer of AZT is known to be much higher, approximately 80%. The authors concluded that a Phase II trial of ddI monotherapy or a combination regimen including ddI should be done.

Livingston E and others. Placental transfer of didanosine and initial evaluation of didanosine toxicity in HIV-1 infected pregnant women and their offspring. CROI. Abstract 226.

Page last updated 5 May 1998