From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: VA Summary 4/24/92
Note: non-commercial reproduction.
Archive-Number: 5902
Organization: UCLA, Computer Science Department
Date: Sat, 15 Aug 92 08:13:18 PDT

This AIDS Information Newsletter was obtained from the HIV/AIDS Info
BBS (714) 248-2836.  It is the best source of AIDS Info available.
************************************************************************
                   AIDS INFORMATION NEWSLETTER
                   Michael Howe, MSLS, Editor
                     AIDS Information Center
                VA Medical Center, San Francisco
                     (415) 221-4810 ext 3305
                         April 24, 1992 

                        TABLE OF CONTENTS 
"A Controlled Trial of Early Versus Late Treatment with Zidovudine in 
Symptomatic Human Immunodeficiency Virus Infection" "The Second 100,000 
Cases if AIDS: United States, June 1981- December 1991" "Foscarnet 
Approved for AIDS Patients with CMV Retinitis"  "Public Health Clinic 
Prudent Pharmaceutical Purchasing Act Passed" "AMA Policy for Testing 
HIV" "Fluconazole Successful Drug for Cryptococcal Meningitis"  "Study 
Shows Promise of Fluconazole for Treatment of AIDS-Related Cryptococcal 
Meningitis"  "A Controlled Trial of Fluconazole or Amphotericin B to 
Prevent  Relapse of Cryptococcal Meningitis in Patients With the 
Acquired  Immunodeficiency Syndrome"  
 A CONTROLLED TRIAL OF EARLY VERSUS LATE TREATMENT WITH ZIDOVUDINE IN 
SYMPTOMATIC HUMAN IMMUNODEFICIENCY VIRUS INFECTION (Hamilton JD, 
Hartigan PM, Simberkoff MS et. al.) 
Abstract Background.  Zidovudine is recommended for asymptomatic and 
early symptomatic human immunodeficiency virus (HIV) infection. The best 
time to initiate zidovudine treatment remains uncertain, however, and 
whether early treatment improves survival has not been established.  
Methods.  We conducted a multicenter, randomized, double-blind trail 
that compared early zidovudine therapy (beginning at 1500 mg per day) 
with late therapy in HIV infected patients who were symptomatic and had 
CD4+ counts between 0.2x10(9) and 0.5x10(9) cells per liter (200 to 500 
per cubic millimeter) at entry. Those assigned to late therapy initially 
received placebo and began zidovudine when their CD4+ counts fell below 
0.2x10(9) per liter (200 per cubic millimeter) or when the acquired 
immunodeficiency syndrome (AIDS) developed.  
Results.  During a mean follow-up period of more than two years, there 
were 23 deaths in the early-therapy group (n=170) and 20 deaths in the 
late-therapy group (n=168) (p=0.48; relative risk [late vs. early], 
0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-
therapy group, 28 patients progressed to AIDS, as compared with 48 in 
the late-therapy group (p=0.02; relative risk, 1.76; 95 percent 
confidence interval, 1.1 to 2.8). Early therapy increased the time until 
CD4+ counts fell below 0.2x10(9) per liter (200 per cubic millimeter), 
and it produced more conversions from positive to negative for serum p24 
antigen. Early therapy was associated with more anemia, leukopenia, 
nausea, vomiting, and diarrhea, whereas late therapy was associated with 
more skin rash.  
Conclusions.  In symptomatic patients with HIV infection, early 
treatment with zidovudine delays progression to AIDS, but in this 
controlled study it did not improve survival, and it was associated with 
more side effects. 
Placebo controlled trails have demonstrated that zidovudine reduces 
morbidity and mortality when administered to patients with human 
immunodeficiency virus (HIV) infection late in the course of their 
infection, and that this drug also reduces morbidity when administered 
to symptomatic or asymptomatic patients earlier in the course of 
infection. The best time to initiate zidovudine therapy remains unknown, 
however.  
We conducted a four-year multicenter, randomized, double-blind trail to 
evaluate when to administer zidovudine. Specifically, we wanted to 
determine the long-term clinical benefits and liabilities of earlier as 
compared with later therapy in symptomatic patients with HIV infection 
whose CD4+ counts were between 0.2x10(9) and 0.5x10(9) cells per liter 
(200 to 500 per cubic millimeter). (New England Journal of Medicine, 
1992 Feb 13;326(7):437-43). 

                THE SECOND 100,000 CASES OF AIDS
             UNITED STATES, JUNE 1981-DECEMBER 1991 
     The first cases of acquired immunodeficiency syndrome (AIDS) were 
reported in June 1981 (CDC. Pneumocystis pneumonia--Los Angeles. MMWR 
1981;30:250-2). From 1981 through December 1987, 50,000 AIDS cases had 
been reported to CDC, and by August 1989, 100,000 cases had been 
reported (CDC. First 100,000 cases of acquired immunodeficiency 
syndrome--United States. MMWR 1989;38:561-3). From September 1989 
through November 1991, state and territorial health departments reported 
100,000 additional cases. By December 31,1991, a cumulative total of 
206,392 cases had been reported, and the cumulative number of reported 
deaths  associated with AIDS was 133,232. This report represents 
characteristics of the first and second 100,000 persons with AIDS.
     Overall, most reported AIDS cases occurred among 
homosexual/bisexual men (i.e., men who reported sexual contact with 
other men) (59%) and injecting-drug users (IDUs) (22%). Of the first 
100,000 reported AIDS cases, 61% occurred among homosexual/bisexual men 
with no history of IDU, and 20%, among female or heterosexual male IDUs. 
In comparison, of the second 100,000 reported cases, 55% occurred among 
homosexual/bisexual men with no history of IDU, and 24% occurred among 
female or heterosexual male IDUs.
     The second 100,000 cases reflect an increasing proportion of 
persons with AIDS who have been reported to have had heterosexual 
exposure to persons at risk for human immunodeficiency virus (HIV) 
infection. Of the first 100,000 persons with AIDS, 5% were attributed to 
heterosexual transmission, compared with 7% among the second 100,000--a 
44% increase. Of all AIDS cases among women, 34% were attributed to 
heterosexual transmission, and women accounted  for 61% of all cases 
attributed to heterosexual transmission. Of the first 100,000 persons 
with AIDS, 9% were women, compared with 12% of the second 100,000 
persons. The first 100,000 persons with AIDS included 1683 children, of 
whom 81% were born to mothers with or at risk for HIV infection; the 
second 100,000 persons with AIDS included 1702 children, of whom 87% 
were born to mothers with or at risk for HIV infection.
     A disproportionate number of AIDS cases continue to be reported 
among blacks and Hispanics. Of the first 100,000 reported cases, 27% 
occurred among blacks and 15% among Hispanics. Of the first 100,000 
reported cases, these proportions increased to 31% and 17% for blacks 
and Hispanics, respectively.
     The proportion of AIDS cases related to transfusions as a mode of 
exposure declined in both adults (2.5% to 1.9%) and children (11% to 
5.6%) from the first to the second 100,000 cases. 
Reported by: Surveillance Branch, Division of HIV/AIDS, National Center 
for Infectious Diseases, CDC. 
Editorial Note: The cumulative total of more than 200,000 reported AIDS 
cases emphasizes the rapidly increasing magnitude of the HIV epidemic in 
the United States. the first 100,000 cases were reported during an 8-
year period, whereas the second 100,000 cases were reported during a 2-
year period.
     The number and proportion of AIDS cases associated with 
heterosexual transmission of HIV has been increasing steadily.  Factors 
associated with an increased risk for heterosexual transmission include 
multiple sex partners and the presence of other sexually transmitted 
diseases. In the United States, men and women who have unprotected 
sexual contact, particularly with partners known to have risks for HIV 
infection, are at increased risk for HIV infection. A recent analysis of 
expected trends in AIDS cases in the United States suggests that by 
1995, the infection rate among nondrug-using heterosexual men and women 
may be associated with a doubling of AIDS cases acquired through 
heterosexual transmission (Brookmeyer R. reconstruction and future 
trends of the AIDS epidemic in the United States. Science 1992;253:37-
42).
     Of the estimated 1 million HIV-infected persons in the United 
States, approximately 20% have developed AIDS. Approximately half of all 
persons who have been diagnosed with HIV infection and who have evidence 
of severe immunosuppression (i.e., CD4+ counts <200) meet the current 
AIDS surveillance case definition (Farizo KM, Buehler JW, Berkelman RL. 
Leading non-AIDS defining systemic infections in HIV-infected persons 
[Abstract]. In: Program and  abstracts of the 119th annual meeting of 
the American Public Health  Association. Washington, DC: American Public 
Health Association, 1991:107). Approximately 125,000 persons who do not 
have an AIDS- defining illness are estimated to have a CD4+ lymphocyte 
count <200 (CDC, unpublished data). CDC has proposed expanding the AIDS 
surveillance case definition to facilitate more complete reporting of 
all persons with severe HIV-related immunosuppression and who are at the 
highest risk for developing serious illnesses or death (CDC. Extension 
of public comment period for revision of HIV infection classification 
system and expansion of AIDS surveillance case definition. MMWR 
1991;40:891).  MMWR 1992;41:28-9. 

     FOSCARNET APPROVED FOR AIDS PATIENTS WITH CMV RETINITIS 
     The FDA has approved foscarnet sodium injection (Foscarnet, ASTRA 
Pharmaceuticals, Westborough, Mass.) for the treatment of 
cytomegalovirus (CMV) retinitis in patients with acquired 
immunodeficiency (AIDS).  The safety and effectiveness of foscarnet have 
not been established for treatment of other CMV infections (e.g., 
pneumonitis, gastroenteritis); congenital or neonatal CMV  disease; or 
non-immunocompromised individuals.
     Foscarnet is the second drug approved for use in AIDS patients with 
CMV retinitis.  Ganciclovir was approved in June, 1989, but a 
significant number of patients are unable to tolerate it due to 
neutropenia.  Neither drug is a cure for CMV retinitis in patients with 
AIDS.
     The major toxicity of foscarnet is renal impairment , which occurs 
to some degree in most patients.  Because of this, dose adjustment for 
decreased baseline renal function and any change in renal function 
during treatment is necessary.
     The product's approved labeling includes detailed "patient 
monitoring and "information for patients: sections.  (From the Food and 
Drug Administration. 1991 Dec 18, JAMA, 266(23):3263). 
Editor's Note:  Written inquiries may be directed to the Office of 
Health Affairs, FDA, Parklawn Building, 5600 Fishers Lane, Rockville, MD 
20857. 
See, also, The Treatment of Cytomegalovirus in AIDS--More Than Meets Eye 
[editorial] and Mortality in Patients with the Acquired Immunodeficiency 
Syndrome Treated with Either Foscarnet or Ganciclovir for 
Cytomegalovirus Retinitis.  New England Journal of Medicine.  1992 Jan 
23;326(4):264-5 and 213-20. 

Newsgroups: sci.med.aids