Gerald Friedland

Acquired Immunodeficiency Syndrome: Ophthalmic Manifestations in Ambulatory Patients

Twenty-five ambulatory patients with acquired immunodeficiency syndrome (AIDS) were studied over a 6-month period. Fourteen (56%) of the patients were heterosexuals with a history of intravenous drug abuse. Ocular involvement was seen in 40% of patients, cotton-wool spots being the major manifestation. Findings consistent with cytomegalovirus retinitis were seen in only one patient. Ophthalmologists should be aware of the ocular findings and epidemiology of AIDS.

A prospective longitudinal study of neuropsychological and psychosocial factors in asymptomatic individuals at risk for HTLV-III/LAV infection in a methadone program: preliminary findings.

To test the hypothesis that cognitive impairment may be present early in the course of HTLV-III/LAV infection, intravenous drug abusers (IDVAs) without overt symptoms of AIDS related illness were tested with standard neuropsychological and psychosocial measures. This study is the baseline for a prospective longitudinal study of the natural history of HTLV-III/LAV infection in this high risk population. Of 211 subjects initially evaluated, 70 (33%) were HTLV-III/LAV seropositive and 141 (67%) were seronegative. At the baseline, by univariate analysis, the seropositive IVDAs were significantly (p less than .05) more impaired than seronegatives on 4 of 8 measures: Finger Tapping--dominant, hand, Digit Span Forward, Trail making A and WAIS-Similarities. However, by multivariate analysis the seropositives were significantly more impaired only on the WAIS-Similarities and Wechsler--Associative Learning tests. Multiple factors such as drug use and psychological stress may have influenced test performance. These preliminary results, however, suggest that seropositive IVDAs may show evidence of impaired neuropsychological function even in the absence of AIDS related symptoms and are consistent with the hypothesis of the early neurotropism of HTLV-III/LAV.

A prospective four-year follow-up of neuropsychological function in HIV seropositive and seronegative methadone-maintained patients

The evolution of central nervous system (CNS) impairments associated with human immunodeficiency virus (HIV) infection was assessed by a prospective, longitudinal study of patients in a methadone maintenance clinic. At a mean of 47 months after baseline testing, which included physical exams, HIV antibody testing and a neuropsychological (NP) screening battery, 121 subjects received a second NP assessment. Forty subjects (33%) who were seropositive at baseline showed statistically significant declines in NP function over the 4 years compared with 81 seronegatives, on the Finger Tapping and Trail Making B tests. This relatively long-term follow-up suggests that subtle cognitive deficits develop over time and can be identified early, but their course is slow and appears generally to parallel that of non-CNS symptoms/signs of HIV infection.

Serologic, immunologic, and clinical features of parenteral drug users from contrasting populations

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios. Over 6 months, 1 seropositive patient with a low ratio developed oral thrush and weight loss. We also studied 13 parenteral drug users hospitalized for conditions other than AIDS. Eight had low T-cell ratios, and at least 6 of these developed AIDS or ARC within 4 months. Serum from 8 of 13 inpatients was available for HTLV-III testing: 6/8 were seropositive and 3 of these 6 were among those developing AIDS or ARC. Abnormal T-cell ratios among all patients were associated with abnormal HTLV-III serology (p = .02). Of the 7 patients who developed AIDS or ARC, 4 were tested for both antibodies and T-cell ratios: all 4 were seropositive and had low ratios. A low ratio (p = .0004), a positive ELISA (p = .014), and abnormalities of both tests (p = .001) were associated with the development of AIDS or ARC. Of the 26 patients without AIDS or ARC, 3 were lost to follow-up and 23 did not develop AIDS or ARC. Six of these 26 had abnormal ratios. Of the 21 patients who did not develop AIDS or ARC and who were tested for HTLV antibodies, 2 were lost to follow-up. Seven of 21 were seropositive and 2/21 were both seropositive and had a low ratio. One of these 2 seropositive patients with low ratios also had lymphadenopathy, but he was lost to follow-up. The other had no adenopathy and remained well until her death from trauma a year later. This study found two populations with very different risks. Six of 13 hospitalized parenteral drug users and only 1 of 20 healthy outpatients developed AIDS or ARC.

AIDS research: the ethics of clinical trials.

Research on AIDS involving human subjects poses in stark form a familiar dilemma: Can the demands of a rigorous scientific research design be met without violating the rights or harming the interests of research subjects? The dilemma is especially troubling in the early phases of drug research, when promising medications showing some signs of success in combatting this fatal disease must be tested for safety and efficacy. The research design using randomized controlled trials, in which an experimental drug is tested against a placebo, highlights the dilemma. Although the use of this research design does not pose the only ethical problem for AIDS research, it is perhaps the most dramatic. Related ethical issues include the question of when an experimental drug that holds out the only present hope may be released for general use; who should be selected to receive experimental drugs that are in short supply; how much information should be released about safety and efficacy while a clinical trial is still in progress; and what factors determine the appropriateness of early termination of a study. Medical scientists, policy-makers, and other writers are sharply divided on the answers to these questions. Soon after it was announced that azidothymidine (AZT) shows promise in the treatment of AIDS, sides became polarized. Mathilde Krirn, a research biologist and chair of the AIDS Medical Foundation in New York, became one of the staunch advocates for making the drug available immediately. She was reported as saying: “In the case of AIDS, it’s immoral to give people nothing at all when there is something that could do them good.”’ An opposing view was stated by Harry Schwartz, writer-inresidence at Columbia University College of Physicians and Surgeons. “The double-blind randomized trial is our best instrument for separating real drug effectiveness from transient, chance phenomena,” he commented. “We should not abandon it when we need its help so much against this terrible killer.”’ These opposing views, echoed by other commentators, appear to pit the interests of science against those of AIDS sufferers. It would seem that good science and good ethics are in conflict, but that apparent conflict is easily dispelled. Both sides in the debate rest their arguments on moral considerations. Samuel Broder, head of the AIDS drug-selection committee at the National lnstitutes of Health, was quoted as saying: “There are serious errors-irredeemable errors-that can be introduced if we don’t undertake appropriately controlled studies. It would be a catastrophe if we dismissed a ‘good drug’ or if we allowed a ‘bad drug’ to become the standard of therapy.”’ And Jerome Groopman, an AIDS researcher at Harvard Medical School, noted that “[tlhere are drugs that look absolutely wonderful in the test tube, but are not only ineffective but dangerous.”‘ With opponents in this controversy each defending their approach with ethical arguments, how can their positions be adjudicated? Is one side more “ethically correct,” and the other less so? Does the dispute rest on a conflict of moral principles? On different value priorities? Or on different assessments of what is demanded by properly designed scientific research? By their very nature, ethical dilemmas resist easy resolution, but a careful analysis shows that there is less difference between these disputants than appears at first. The speed with which research proceeds and the numerous investigations currently under way wil1 no doubt put some of these questions to rest. For example, as Dr. Broder has observed, “once an effective drug is found, it will become a standard of therapy against which all future drugs will be tested-eliminating the need for any more placebos.”s Although that development will eliminate the need for controlled trials using an inert substance known to be ineffective in controlling the disease, it will not entirely resolve the research dilemma. The debate will then shift to the ethics of using a less effective drug on some patients, while others are randomized to the newer, more promising medication. However, many unanswered questions remain, both

Risk of transmission of HIV to home care and health care workers

There are only three known routes of transmission of the human immunodeficiency virus (HIV): (1) exposure to blood via transfusion, sharing of contaminated needles by drug abusers, occupational needle stick or blood spill, unsterile needle injections; (2) sexual transmission; (3) perinatal exposure. There is no evidence for transmission by close interpersonal nonsexual contact or insect vectors. Health care workers are at risk for HIV transmission through accidental parenteral inoculation or extensive exposure to blood on nonintact skin or mucous membranes. Fortunately, population studies indicate that this risk is low and may be further reduced by adherence to simple infection control guidelines. The accumulated information on low rates of occupational transmission of HIV makes unwarranted the treatment of patients with acquired immunodeficiency syndrome (AIDS) or HIV infection as if they were highly contagious in the health care setting.

The acquired immunodeficiency syndrome: general overview.

Early in his novel “The Plague” (La Peste), Albert Camus describes the unpreparedness and disbelief of a population confronted with the onset of an epidemic. He tracks the course of the disease on both its victims and the population at large, paying particular attention to the response of ordinary citizens to a catastrophy within their midst. The disease and its effects upon people becomes a metaphor for the human condition. There are strikingly similar parallels in the unfolding story of the Acquired Immunodeficiency Syndrome (AIDS). This disease, only five years since its recognition, has produced an extraordinary medical chronicle, with enormous consequences for clinical medicine, virology, immunology, neurobiology and the public health yet to be fully assessed. In addition, the social implications of this new disease are of unprecedented complexity and interest.