AIDSWEEKLY Plus; Monday, October 12, 1998
Daniel J. DeNoon, Senior Editor

The study, a clinical endpoint trial of 996 previously untreated HIV patients in Brazil, included 277 women (28 percent of total patients), constituting one of the largest representations of women in a long-term protease inhibitor study in the world, according to drug manufacturer Merck.

The study, presented at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in late September 1998 in San Diego, California, also showed that, in both genders, the regimens containing Crixivan resulted in marked decreases in viral RNA and increases in CD4 cell counts.

"This is the first analysis of its kind that clearly shows that combination therapy with a potent protease inhibitor can produce dramatic reductions in clinical events in women," said Dawn Averitt, AIDS treatment advocate and founder of WISE, the Women Information Service Exchange. "Women living with HIV now have additional evidence to make informed decisions about their treatment choices."

The objective of the analysis was to determine whether there was consistency of treatment effects across gender in patients treated with Crixivan plus AZT (zidovudine; Retrovir(R)) (200 mg every eight hours) or Crixivan monotherapy (800 mg every eight hours) compared to those treated with AZT alone (3TC [lamivudine; Epivir(R)] was added to both regimens containing AZT over the course of the study).

For both men and women, the number of HIV patients progressing to an AIDS-defining illness or death was consistently less in the arms of the study with Crixivan. Overall, 13 of the 93 women (14 percent) and 50 of the 239 men (21 percent) treated with AZT alone experienced an AIDS-defining illness or died during the course of the study.

This compared to markedly lower incidences of disease progression and death among seven of 90 women (7.8 percent) and 14 of 242 men (5.8 percent) treated with Crixivan and AZT who experienced clinical events, and four of 94 women (4.3 percent) and 24 of 238 men (10 percent) treated with Crixivan alone.

"This study demonstrated that Crixivan has antiretroviral activity in both women and men in terms of decreased disease progression, decreased viral RNA, and increased CD4 cell counts," explained Randi Leavitt, MD, Merck Research Laboratories. "These results add to the weight of scientific and medical evidence supporting the overall impact of potent protease inhibition on the management of HIV disease, and adds to our understanding of effective management of HIV disease in women, who are, unfortunately, a rapidly growing segment of the infected population in the United States."

According to the U.S. Centers for Disease Control and Prevention (CDC), between 1995 and 1997, HIV incidence among women increased by 17 percent. The CDC also reported in June 1996 and again in January 1997 the first declines in the rates of AIDS-related deaths since the beginning of the HIV epidemic. The declines have been largely attributed to the use of protease inhibitors in triple therapy with reverse transcriptase inhibitors. The estimated number of deaths among women with AIDS decreased by 13 percent in 1996, however the most significant decline was among white males, 33 percent.

The overall occurrence of clinical events among women in this study was 8.6 percent for women and 13.8 percent for men. "This difference is probably not treatment-related," explained Leavitt. "It may be a reflection of the somewhat better immune status of the women who enrolled in the study."

In general, females had higher C134 cell counts and lower viral burdens at baseline than men. The median CD-4 cell count for female patients was 161 cells/mm(3) at study entry; for men, it was 142 cells/mm(3). Baseline median viral load for all enrollees was 31,000 copies/mL.

Changes in viral load and CD4 cell counts among both male and female patients in the study underscored the treatment benefits of potent protease inhibition with Crixivan regardless of gender. Approximately 26 percent of female patients treated with Crixivan alone and 27 percent of patients on the combination of Crixivan and AZT had viral levels below detection (less than 500 copies/mL) at week 48 (median follow-up week). Approximately 49 percent of men treated with Crixivan plus AZT and 32 percent treated with Crixivan alone had undetectable viral loads. No more than 13 percent of females or 10 percent of men on AZT alone had viral loads of less than 500 copies/mL at any point in the study.

There were marked treatment differences in average CD4 call count increases over the follow-up period among women (68 cells/mm(3)) and men (99 cells/mm(3)) treated with Crixivan and AZT versus AZT alone, Similar relative improvements in CD4 cell counts were seen in the women (62 cells/mm(3)) and men (91 cells/mm(3)) treated with Crixivan versus AZT monotherapy.

Treatment with Crixivan in the study was generally well-tolerated. Ninety patients (9 percent) had adverse experiences associated with kidney stones: 40 (12.1 percent) in the Crixivan plus AZT group, 40 (12.1 percent) in the Crixivan group, and 10 (3 percent) in the AZT group. No patients discontinued due to adverse experiences associated with kidney stones. The proportion of women with kidney stone- associated adverse experiences was less than that observed in men for all treatment groups.
981012
AW981007

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .