Subject: Treatment Issues Vol. 5 No. 1 Date: Jan 10 1991 (736 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Treatment Issues 51 Volume 5 Number 1 -- Jan. 10, 1991 Copyright 1991 Gay Men's Health Crisis, Inc. All rights reserved. Permission granted for non-commercial use. Non-commercial reproduction is encouraged. Contents: [items are separated by "*****" for this display] Peptide T Access Blocked Clinical Manifestations of HIV Infection in Women ddI/ddC Licensing Update Ampligen Update Richard Dunne In Brief Footnotes Masthead ***** Peptide T Access Blocked Wayne Kawadler We hear more about the controversies surrounding the clinical trials, patent disputes and availability of Peptide T than the actual efficacy of the drug. Since Treatment Issues last checked in with Peptide T, which has had a rather rocky history, access problems have developed. After the phase I trials in Provincetown and Boston, continued availability of the drug for trial participants became a major controversy. Trial participants were afraid they would be unable to obtain drug after the trial ended. In addition, Bristol Myers withdrew its sponsorship leaving Peptide T without a financial backer. After several rounds of sometimes heated negotiations with community health officials and activists, the National Institute of Mental Health (NIMH) picked up the funding to extend the phase I trial and to provide drug to the participants after completion of the trial. As Treatment Issues went to press, more negotiations were underway, this time regarding patent issues and sponsorship of clinical trials. In addition, recent posturing by the FDA has threatened underground sources of the drug. People who have relied on buyers' clubs to obtain Peptide T for their personal use are understandably agitated. History Peptide T is thought to work by blocking the entry of HIV into cells bearing the CD4 receptor, a passageway into the cell to which HIV is strongly attracted. In that regard, Peptide T is similar to the drug CD4. Peptide T easily enters the brain and has been particularly associated with improvement of neurological symptoms. Several small studies claim that Peptide T reverses neuropsychiatric symptoms associated with HIV infection (1). Also, stabilization of T4 cell counts have been reported. None of the participants in these studies experienced toxicity. These interesting results prompted buyers' clubs (groups that help procure unapproved drugs for individuals) to obtain Peptide T. Buyers' clubs in Dallas and Ft. Lauderdale have been facilitating access to Peptide T for their clients. The New York PWA Health Group has considered helping people obtain Peptide T, but not much interest has been expressed in the drug, according to Derek Hodel, the group's Director. Community Availability A source of Peptide T for buyers' clubs in the United States has been Peninsula Labs, a pharmaceutical company in California. Several buyers' clubs created a dummy animal trial, in order to gain access to the drug. Pharmaceutical companies can sell unapproved drugs to groups conducting animal research. The Food and Drug Administration (FDA) informed Peninsula that the Peptide T being sold to buyers' clubs was actually being used by people and that the commerce must stop. Recently, representatives of the FDA visited Peninsula Labs, interrogated employees of the company and searched through sales records (2). Eng Tau, a spokesperson for Peninsula Labs, claims that she would gladly supply drug to whoever requested it, if the FDA would allow her to do so. Legal Action Ron Woodroof of the Dallas Buyers' Club filed a law suit against the FDA, requesting a temporary restraining order and an injunction against the agency's actions to stop Peninsula Labs from selling Peptide T to Dallas Buyers' Club. District Court Judge Charles Legge ruled against Woodroof and wrote in his opinion that the law does not provide unlimited access to experimental drugs for people with terminal illnesses. But Judge Legge also wrote of Woodroof, "He ought to have the right to obtain most any drug he believes would help alleviate the situation (3)." Importing Unapproved Drugs Another potential source of Peptide T is Carlbiotech, a Danish pharmaceutical company. Carlbiotech was recently awarded a contract to provide Peptide T for a trial which will take place at the University of Southern California (USC). Interestingly, Carlbiotech also received a letter from the FDA at about the same time the contract was awarded, warning them not to sell the drug to individuals in the United States who do not hold an IND (Investigational New Drug). An IND gives authority from regulatory officials to conduct human research with an experimental drug. An unnamed company employee expressed concern that Carlbiotech's contract with the FDA would be in jeopardy if it sold Peptide T to American buyers' clubs. According to Brad Stone, an FDA spokesperson, a company cannot legally sell an unapproved drug to an individual who does not have an IND (4). If a person is in dire need he/she can apply to the FDA for a "Compassionate Use IND" for access to a drug or can try to enroll in a clinical study. A Compassionate Use IND is only possible with the cooperation of a pharmaceutical company, which is sometimes difficult to obtain. Stone said that the FDA would encourage individuals seeking an unapproved drug to apply for an individual Compassionate IND. However, it is possible to import some experimental drugs for personal use. In July 1988, the FDA issued a paper stating its policy on importation of drugs that are not approved in the United States (5). Individuals are allowed to import such drugs according to the following stipulations: the product must be for personal use; it must be legally available in the country of origin; it cannot be resold; no more than a three month supply can be imported at one time and patients must have a prescription for the medication. In addition, the FDA retains the prerogative to disallow importation of drugs deemed to be too toxic. Buyers' clubs facilitate this process and help patients fill prescriptions for foreign drugs. A strict reading of the FDA import policy would not allow importation of Peptide T from Denmark since the drug is not licensed there, and an FDA spokesperson indicated that shipments of Peptide T could be stopped at the border (6). Meanwhile people who are buying Peptide T from buyers' clubs are very frightened and angry that their access to the drug may be interrupted. One person who has asked to remain anonymous says: "I have less than 30 days worth of drug left and I am down to limited resources. But I will not tolerate and will not let a mindless and depersonalized bureaucracy compromise my life. I was diagnosed with AIDS six years ago and I intend to live." Planned Trials A phase II trial may soon be accruing patients to examine Peptide T's effect on neuropsychiatric symptoms. This trial will be conducted at the University of Southern California (USC). Funded by the NIMH, the trial will enroll 150 patients with moderate to severe cognitive impairment. The current protocol (trial guidelines) calls for two arms: Peptide T versus placebo for six months. Participants will also be allowed to take other antivirals. Any participant receiving placebo whose neurological symptoms worsen will be switched to drug. As Treatment Issues went to press, the protocol had not yet been finalized. The contract for the trial was awarded to USC in September; this lethargic protocol approval process is indicative of the unhurried pace at which this drug has been developed. For further information about this trial call Charles Hovis at (212) 226-4643. A second Phase II trial for Peptide T is currently recruiting patients at Yale University Medical Center in New Haven. This trial is for intravenous drug users (IVDUs), who are taking AZT. The study will last five years, accruing twenty-four patients a year. The National Institute of Drug Abuse is funding the trial in collaboration with the NIMH. For more information call Brenda Martini at (203) 772-0191. What Now? It is unclear if the FDA is embarking on a general assault on the underground's providing access to unapproved drugs. The nervousness of people who have been taking Peptide T could be easily alleviated if the FDA chooses to uphold the spirit of its own import policy. Given Peptide T's apparent lack of toxicity, it is puzzling that the FDA would be vigilant about personal use of the substance outside of clinical trials. We will continue to cover this story as it unfolds. ***** Clinical Manifestations of HIV Infection in Women Mary Beth Caschetta The World Health Organization (WHO) estimates that worldwide more than one-third of persons infected with HIV are women. In merely a decade from now, the annual number of AIDS cases in women will probably equal that in men, making women, both nationally and internationally, the population currently being infected with HIV at the fastest rate (7,8). Due to insufficient funding and lack of focus, information about HIV infection in women is sparse, but some generalizations can be made. For instance, Kaposi's sarcoma (KS), which is common in gay and bisexual men who contract HIV infection sexually, rarely occurs in women (9). Also, two-thirds of women who progress to clinical AIDS are found to have pneumocystis carinii pneumonia (PCP) by the time they are first diagnosed with AIDS, which usually occurs late in the course of their illness (10). Female patients may also experience fever, night sweats, cough and weight loss. But the classical early manifestations of AIDS in women are usually gynecological complications, such as chronic vaginal yeast infections, anal or genital warts and ulcers, herpes simplex virus, and pelvic inflammatory disease. Notably, the Centers for Disease Control (CDC) definition of AIDS does not include any of these gynecological symptoms, which are known to occur with frequency and severity in women with AIDS. In July 1990 the CDC published a study stating that 65 percent of HIV- infected women died without fitting the CDC definition for AIDS (11). The ramifications of such underrepresentation are enormous: women are denied disability benefits to which they are entitled; their illness goes misdiagnosed and untreated; and research efforts are skewed, distorting general knowledge of the scope of the AIDS epidemic. Currently, women are twice as likely as men to have opportunistic infections (OIs) which are missed or misdiagnosed because HIV infection is not suspected (12). When detection does occur, a woman may progress from an AIDS diagnosis to death twice as fast as a man. In fact, according to CDC reports, trends from 1984- 1990 show that women are more likely than men to die the same month as they are diagnosed with AIDS (13). Clearly, early detection and management of HIV infection in women is critical to improve survival. It is important to note that the following clinical manifestations of HIV infection in women can and should be considered and appropriately addressed, when treating all female patients. Any woman, regardless of her class, color, ethnic origin, pregnancy status, sexual or drug-using history, and sexual identity, deserves proper medical attention and consideration in this matter. Vulvovaginal Candidiasis It is thought that more than one-third of women with HIV infection develop chronic genital yeast infections (14). This condition is caused by an increased growth of yeast that is already established in the vagina by spread of organisms from the anus, or in some cases by sexual transmission. Vulvovaginal candidiasis (yeast infection) may cause severe itching and burning, odor from the vagina, and a "cheesy" discharge. HIV- infected women with candidal vaginitis may experience temporary symptomatic improvement with treatments of antifungal agents, such as intravaginal miconazole or clotrimazole (100 mg once daily for seven days). Clotrimazole will soon be available over-the-counter (Gyne-Lotrimin vaginal inserts, Schering-Plough) for women with vaginal yeast infection (15). This condition may require maintenance therapy in immunosupressed women. Vaginal candidiasis may be the first symptom of HIV infection in women. As T4 cell counts drop, yeast infections may occur with serious consequence in the mouth and throat, and later in the esophagus. Swollen lymph nodes, herpes simplex lesions, and a general lack of energy may also accompany this condition. Fluconazole, a fairly non-toxic but considerably expensive drug, is the recommended treatment for chronic candidiasis in HIV-infected women. Intermittent dosing may be sufficient, but further study is needed. Human Papillomavirus (HPV) and Cervical Cancer The human papillomavirus (HPV) is associated with the development of anogenital warts which may cause blockage, abnormal Pap smears, flat or tiny warts on the cervix, and possibly cancer- causing tissue growths (16). Red, spiked warts on the anal or genital regions, especially in moist areas of frequent genital friction, are not difficult to recognize and may be treated with application of acetic acid, cryotherapy (freezing), laser therapy or surgical removal. Frequent recurrences of warts especially after rigorous treatment (topical 5-fluorouracil (5FU); laser therapy; or alpha interferon injections into the warts) are common and may indicate HIV infection. Inverted warts, dysplasia (abnormal tissue growths) and neoplasia (cancer-causing tissue growths), which can also be caused by HPV, may present more serious problems. Because HPV in HIV-infected women has been found to be strongly associated with genital dysplasia and cancerous growths, detection by frequent Pap smear and colposcopy (a microscopic examination of the vulva, vagina and cervix) is highly recommended for any patient who may be at risk. Recent, alarming reports indicate that Pap smears may not adequately detect abnormal or cancerous cell growth in HIV- infected women, and that cervical biopsy by colposcopic examination may be the preferred means of detection (17). Unfortunately colposcopic exams are costly and not covered by Medicaid. Treatment of any atypical, pigmented, or persistent warts should be initiated only after a biopsy rules out dysplasia. Also recommended is anoscopy (a microscopic examination of the anus) in order to rule out anal warts and cancers. There is some very strong suggestion that HIV disease in women is related to abnormalities in squamous cells in the cervix and vagina which may cause cancer (18). Follow-up examinations and careful surveillance for cervical cancer with Pap smears (and colposcopic exams when possible) should be given every six months for asymptomatic women without dysplasia. Pelvic Inflammatory Disease (PID) Possibly caused by sexually transmitted organisms and thought to be associated with chlamydia (a sexually transmitted bacterial infection), pelvic inflammatory disease (PID) is a painful inflammation of the upper genital tract. Also common to PID are collections of pus in the fallopian tube or the ovary. Abnormal vaginal bleeding, painful and difficult menstruation, infertility and ectopic pregnancy (pregnancy which occurs outside of the uterus) are also possible symptoms of PID. Anecdotal reports suggest that PID is more common and more severe in women with HIV infection, than in women with normally functioning immune systems. PID diagnosis can be made by examining the abdomen with a surgically inserted instrument called a laparoscope. HIV- infected women may be unable to mount an immune response, causing the inflammation and pain by which professionals are able to make a diagnosis. Because there exists no suitable diagnostic test, detection of PID in HIV-infected women may be extremely difficult (19). Immediate hospitalization is strongly recommended, where severe PID is suspected. Since no single treatment is established for PID, professional medical attention is a must. Herpes Simplex Virus (HSV) Chronic herpes lesions may be a symptom of immunodeficiency in women. Genital herpes has also been strongly associated with transmission of HIV infection, possibly due to breaks in the skin allowing entry of the virus into the blood stream. Patients may benefit from oral acyclovir (Zovirax) but maintenance therapy may be necessary. Daily acyclovir is thought to be safe and effective for up to three years (20). Treatment with intravenous acyclovir is reserved for more severe conditions. Other Sexually Transmitted Diseases It has been suggested that genital ulcers caused by conditions, such as genital herpes, chancroid, warts and syphilis increase the risk of HIV transmission for women. Other co-factors that may play a role in the severity and prevalence of sexually transmitted diseases (STDs) include: age of first sexual intercourse; the economic necessity of exchanging sex for drugs and money; number of partners; cigarette smoking, and dietary deficiencies (21). Although further study is needed to establish the connection between STDs and HIV, women should be counseled and tested for STDs at every medical screening. Conclusion Because of the many psychosocial obstacles barring women access to education, technology, health care, fertility control and financial resources, women do not often seek out primary medical care (22). Beyond contraception, abortion, prenatal care and pediatric visits, a woman may have little or no contact with a doctor or clinic (23). Therefore, it is important to note that any contact between a female patient and a health professional is an invaluable opportunity for culturally sensitive risk- assessment of HIV and other STDs; education about transmission of HIV; information about drug and alcohol treatment; and ongoing counseling, support and medical evaluation. A future article will focus on reproductive issues and pregnancy for women with HIV infection. ***** ddI/ddC Licensing Update David Gold In the past two years, AIDS activists have successfully negotiated with the manufacturers of two experimental antiviral drugs, ddI and ddC, to develop expanded access programs. These programs allow for access to the drugs before they become fully licensed, and are for people who do not qualify for clinical trials. The expanded access programs have provided treatment options to thousands of people whose conditions were deteriorating in spite of treatment with AZT. Many other people, however, do not meet the specific medical criteria required to obtain ddI and ddC, even certain individuals who can no longer take AZT due to toxicity or resistance. Now, activists are beginning to focus their energies on obtaining licensing approval for both ddI and ddC, so that everyone who might benefit from these drugs will be able to obtain them. History In November 1989, Bristol Myers-Squibb, the manufacturer of ddI, under pressure from AIDS activists, initiated an expanded access plan. Individuals who were intolerant to, or had failed AZT, and who were unable to qualify for clinical trials, were given access to the drug through their physician. As of December 1990, over 13,000 individuals have obtained ddI through this plan. Hoffman-La Roche, manufacturer of ddC, first announced an expanded access program for its drug in June 1990. Because the plan limited the number of patients to be enrolled in the trial, and also made failure of AZT and ddI a requirement for entry, it was quickly dubbed "a limited access plan" (24). In September 1990, Hoffman-La Roche yielded to pressure from a nationwide coalition of more than 160 AIDS organizations, researchers and physicians, including ACT UP New York, GMHC, and Project Inform. The manufacturer agreed to provide ddC to an unlimited number of individuals who had failed or become intolerant to AZT. As of this date, Hoffman-La Roche claims to have enrolled close to 1,000 people in its ddC access plan. Nevertheless, there are still substantial problems with the plan, which effectively limits the number of people gaining access to ddC. In order to enroll patients in the program, Hoffman-La Roche requires physicians to obtain approval from local Institutional Review Boards (IRBs). An IRB is a hospital committee that decides if an unlicensed drug may be used in its hospital. In comparison, Bristol-Myers Squibb obtained a "blanket" IRB approval from the FDA for its ddI program, eliminating the need for hospitals to make separate, internal decisions. Hoffman-La Roche also requires an overwhelming amount of paperwork to enroll patients in the ddC program, discouraging some physicians from trying to obtain ddC for their patients. More information about the ddC access plan is available by calling 1-800-HIV-21-ddC. Licensing Campaigns Activists will be meeting with Hoffman-La Roche to discuss concerns about the limitations of the ddC expanded access program, in January 1991. Other agenda items for the meeting will include: release of preliminary results from the ddC trials; progress on a New Drug Application for ddC (the paperwork required by the FDA for full licensing of a drug); and the company's plan for developing protease inhibitors, a new class of drug that interrupts HIV replication differently than do AZT, ddI and ddC. The campaign to gain rapid licensing approval for both ddI and ddC is crucial for many persons with HIV and AIDS. For tens of thousands of individuals, AZT is simply too toxic or it is no longer effective due to the development of resistance. Additionally, too many people do not meet the tightly-drawn inclusion criteria for the ddI and ddC access plans. For example, one of the criteria for a diagnosis of "AZT intolerance" is that the patient must become severely anemic on two occasions. Many physicians, however, prefer to give their patients blood transfusions rather than allow them to become so anemic as to manifest symptoms such as severe weakness or dizziness. As a result, many people who cannot continue on AZT will also not qualify for expanded access, and so are left with no effective antiviral therapy option. Activists also point out that more is known about the efficacy and toxicity of ddI and ddC at this point than was known about AZT when it was approved. In addition, many researchers and clinicians believe that the safest and most effective use of nucleoside analogs (the class of drug which includes AZT, ddC and ddI) is with low-dose combinations. Combining AZT and ddC, either in alternating or concurrent doses, is believed to limit toxicity, delay or prevent resistance, and possibly act synergistically to achieve greater efficacy (25,26). Conclusion Given all the factors, activists believe that enough is known about the safety and efficacy of both ddI and ddC to make them available by prescription. Certainly, much more is known about the safety of these two drugs than was known about AZT when it was approved in 1987. The most contentious issue now is how to measure ddI's and ddC's effectiveness by objective laboratory values (or "surrogate markers"). But many clinicians have provided testimony about their patients' improvement while taking these drugs (27) and clinical trials results to date support such claims (28,29). It is worth noting, however, that much of the data on ddC remains unpublished. Unless more papers appear in medical journals, it will be difficult for clinicians who have not followed community publications to use the drug when it is licensed. Patients ought to have the right to make informed choices with their physicians about which treatment regimen to pursue. Without access to ddI and ddC, many patients find themselves in a predicament similar to that faced by people with symptomatic HIV infection before AZT became available by prescription. ***** Ampligen Update Gabriel Torres, M. D. Ampligen is a synthetic form of RNA being studied in patients with cancers that manifest as solid tumors, chronic fatigue syndrome, and HIV infection. Since most RNA is single-stranded, except in certain viruses like HIV, Ampligen may be thought of as an agent which produces a positive immune response in the body, rather than a negative one. Ampligen has activity in the test tube against many viruses including CMV, herpes simplex, human herpes virus Type VI, hepatitis B, and HIV. In addition, Ampligen seems to increase interferon production which in turn stimulates antiviral activity in the immune system, such as the activation of natural killer cells and macrophages (white blood cells). The results of an initial phase I Ampligen trial for seven patients with AIDS and ARC were published in 1987 in the Lancet. The study reported clinical improvements in immune functions such as, restoration of skin test reactivity, reduction of swollen lymph nodes and stabilization or increases in T4 cell counts. Ampligen may also decrease the actual amount of virus in some patients. After these phase I results were published, duPont Pharmaceuticals furnished the much needed funds and joined HEM Research Inc., Ampligen's manufacturer, to sponsor a phase II trial of the drug. In the placebo-controlled phase II study, the significant effects of Ampligen as reported by the phase I trial were not reproduced. The Ampligen used in this later study was formulated in plastic bags for intravenous infusion. Such formulation, HEM claimed, produced a molecule of the drug with different physical and chemical properties than Ampligen prepared in glass bottles. When 20 patients who received Ampligen in the glass bottle formulation were compared to a group receiving placebo, the frequency of opportunistic infection and lymphomas (cancers) was statistically reduced in those receiving drug. Subsequent studies of Ampligen by HEM have shown that the drug retains its activity if prepared and packaged in glass bottles instead of plastic bags. A follow-up unpublished study, conducted by Dr. William Carter showed a synergistic effect (a combined action of two or more drugs that is greater than either drug action on its own) by combining Ampligen and AZT in a group of 11 symptomatic ARC patients. Some of these participants experienced rises in T4 cell counts, which remained elevated for more than one year after the onset of the trial. Test tube experiments also suggest that Ampligen may reduce AZT-related bone marrow toxicity and prevent the emergence of AZT resistance. The side effects of Ampligen have been mild, consisting of light rashes, flushing and a mild flu-like syndrome which improves after several weeks of therapy. New Hope for Ampligen? HEM Research, Inc. is now conducting a multicenter, double blind, placebo controlled study of Ampligen at two doses (400 mg and 700 mg) in HIV-positive persons with T4 cell counts between 100-500 who are taking AZT (300-500 mg/day). Forty-five patients, continuing AZT therapy, will be assigned to either of the two doses of Ampligen, or placebo. Participants will receive intravenous infusion two times per week. Patients with previous AIDS-defining opportunistic infections or lymphoma are excluded since the objective of the study is to determine whether Ampligen decreases progression and stabilizes T4 cell counts, p24 antigen levels, and other measurements of immune function. The study will last 12 months and is being conducted at medical centers in New York, Philadelphia, Miami, Tampa, Houston, Dallas, Washington, D. C. and Portland, Oregon. The local centers include Hahnemann Medical Center in Philadelphia (Jeanine Thomas at (215) 448-8610); and St. Vincent's Hospital in New York City (Michael Thorn at (212) 790-7020, beeper # 2561 or at (212) 790- 7625). For more information, contact HEM Research, Inc. at (215) 988-0080. ***** Richard Dunne, 1944-1990 Richard Dunne, Executive Director of GMHC from 1985-1989, died in Rhode Island on December 29, 1990, of AIDS-related causes. Under Richard's distinguished stewardship, the Medical Information Program was begun in July 1987. Richard named Dr. Barry Gingell Director of Medical Information, a position Barry held until his death in 1989. Richard maintained an ongoing involvement in Treatment Issues and co-authored an article on Progressive Multifocal Leukoencephalopathy (PML), which appeared in vol. 4, no. 6. Richard's efforts were significant in the movement to make treatments more quickly available and accessible to people with AIDS. His clarity of thought, leadership and wit will be greatly missed and will provide inspiration to carry on. ***** In Brief EPO Approved! The FDA approved a license for Protcrit, a synthetic form of erythropoietin (EPO), which significantly reduces anemia in people treated with AZT. A protein formed in the kidneys, EPO stimulates the production of red blood cells. EPO had already been licensed for patients with kidney failure and is marketed by Amgen, a pharmaceutical company, as a product called Epogen. Another company, Ortho Biotech, conducted trials of their version of EPO in people with AIDS. While these trials progressed, Ortho provided free EPO through a Treatment-IND program to people with AIDS. Now, Ortho's drug, with the market name "Procrit", has been licensed for anemia in HIV-infected patients. Procrit is an extremely expensive drug; one dose (7000 units) will cost about $70. Patients typically need three doses a week and Ortho speculates that the annual cost will be from $6000-8500. Ortho says that no one will pay more than $8500 a year, no matter how much drug they need. The company will provide the drug free of charge to people without insurance if their annual income is under $25,000. When a company spokesperson was informed that the AIDS Drug Assistance Program provides certain drugs free to people whose income is below $44,000, she replied, "I'll check into that." Let's hope so. For more information about Procrit, call 1-800-52-37739. For more information about indigent patient programs, call 1-800- 553-3851. ***** Footnotes 1) VIth International Conference on AIDS abstracts SB. 459, SB. 501, SB. 505, 2183, San Francisco, June, 1990. 2) Personal communication, E. Tau. 3) Doyle, J. AIDS patient loses challenge to drug ban. San Francisco Chronicle, p. A4, Dec 4, 1990. 4) Personal communication, B. Stone. 5) FDA Talk Paper: Policy on importing unapproved AIDS drugs for personal use. July 27, 1988. 6) Personal communication, B. Stone. 7) World AIDS Day Newsletter. World AIDS Day 1990: The Global Response. 2:Sept/Oct, 1990. 8) CDC Update: Heterosexual Transmission of AIDS and HIV -- United States. MMWR 38:423-424, 1989. 9) Smith M. Opportunistic infections and malignancies. National Conference on Women and HIV infection, Washington, D. C., 1990. 10) Osborne NG. HIV Infection in Women. Clin Prac Gynecol 1:129- 140, 1989. 11) Chu S. HIV and mortality in women. JAMA 264:225-29, 1990. 12) Me First: Medical Manifestations of HIV in Women, New Brunswick, NJ: New Jersey Women and AIDS Network, 1990. 13) Berkelman R. Epidemiology: defining the problems and targeting the response. National Conference on Women and HIV Infection, Washington, D. C. 1990. 14) Osborne NG. HIV Infection in Women. Clin Prac Gynecol 1:129- 140, 1989. 15) Nightingale S. Clotrimazole available without a prescription for vaginal yeast infection. JAMA 265:, 1991. 16) Byrne M et al. The common occurrence of human papillomavirus infection and intraepithelial neoplasia in women infected by HIV. AIDS 3:379-382, 1989; and Feingold, A et al. Cervical cytologic abnormalities and papillomavirus in women infected with HIV. J AIDS 3:896-903, 1990. 17) Ellerbock T. and Schuman P. National Conference on Women and HIV infection, Washington, D. C., 1990. 18) Schrager L et al. Cervical and vaginal squamous cell abnormalities in women infected with HIV. J AIDS 2(6): 570-575, 1989. 19) Guinan M. Gynecoligical manifestations of HIV disease. National Conference on Women and HIV infection, Washington, D. C., 1990. 20) Me First: Medical Manifestations of HIV in Women, New Brunswick, NJ: New Jersey Women and AIDS Network, 1990. 21) Schuman P. Gynecoligical manifestations of HIV disease. National Conference on Women and HIV infection, Washington, D. C., 1990. 22) Denenberg R. Unique aspects of HIV infection in women. Women, AIDS and Activism, p.31 South End Press, 1990. 23) Denenberg R. Women and HIV-related Conditions. Treatment and Research Forum, 2. CRI tel (212) 481-1050. 24) "Expanded Access to ddC" Treatment Issues 4(4), 1990. 25) Personal communication, M. Fischi. 26) Personal communication, G. Skowron. 27) Bach MC. Clinical response to ddI in patients with HIV infection resistant to zidovudine. NEJM 323(4):275, 1990. 28) Yarchoan R. et al. Long-term toxicity/activity frofile of ddI in AIDS or AIDS-related complex. Lancet 336:526-9, 1990. 29) Merigan TC. et al. Circulating p24 antigen levels and responses to ddC in HIV infections. Ann Intern Med 110:189-94, 1989. ***** Treatment Issues is GMHC's newsletter devoted to providing reliable information on experimental AIDS therapies. Describing an experimental therapy should not be construed as recommending it. All new treatments should be done under a physician's care. Treatment Issues is published ten times yearly. Copyright 1991 Gay Men's Health Crisis, Inc. All rights reserved. Non- commercial reproduction is encouraged. Subscription lists are kept confidential. Editor: Kevin Armington Associate Editor: Mary Beth Caschetta Medical Consultant: Gabriel Torres, M. D. Technical Assistance: Wayne Kawadler Writers: Mary Beth Caschetta David Gold Wayne Kawadler Gabriel Torres, M. D. GMHC, Department of Medical Information, 129 West 20th Street, New York, NY 10011. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display