Linda Laubenstein

Disseminated Kaposi's Sarcoma in Homosexual Men

Nineteen cases from an epidemic of disseminated Kaposis sarcoma in homosexual men were studied by clinical, virologic, immunologic, and genetic methods. The patients were all male homosexuals ranging in age from 29 to 52 years, with histories of multiple sexually transmitted diseases and exposure to both prescription and recreational drugs. Sites of disease included skin (16 of 19 patients), lymph nodes (13 patients), gastrointestinal tract (12 patients), spleen (three patients), and lung (one patient). Most patients had elevated levels of serum immunoglobins, positive antibody titers to hepatitis A and B virus, cytomegalovirus and Epstein-Barr virus, and impairment of cell-mediated immunologic reactions. The frequency of HLA-DR5 in these patients was significantly elevated. Two of the 19 patients died. Although the precise cause of this epidemic is unknown, it is likely that a genetic predisposition, an acquired immunoregulatory defect, and one or more infectious agents and drugs may be involved.

Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS

The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS.

National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results

To identify risk factors for the occurrence of Kaposis sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposis sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposis sarcoma and pneumocystis pneumonia.

RISK FACTORS FOR KAPOSI'S SARCOMA IN HOMOSEXUAL MEN

An investigation of 20 homosexual men with histologically confirmed Kaposis sarcoma and 40 controls revealed significant associations between Kaposis sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposis sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).

Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia

We studied the effects of long-term (12 months) dronabinol in 94 late-stage acquired immunodeficiency syndrome (AIDS) patients (mean CD4 count of 45/mm3) who previously participated in a 6-week study (placebo versus dronabinol). All patients received dronabinol orally-2.5 mg twice daily (90%) or 2.5 mg once daily (10%). Appetite was measured using a visual analogue scale for hunger (VASH). Dronabinol was associated with consistent improvement in mean appetite. Patients previously treated with dronabinol continued to show improvement in VASH (percent change from baseline of 6-week trial: 48.6-76.1% at each month), whereas those previously treated with placebo exhibited substantial improvement in mean appetite, particularly during the initial 4 months of treatment (48.5-69.9%). Thereafter, dronabinol was associated with a VASH change at least twice baseline. Patients tended toward stable body weight for at least 7 months. Adverse events were primarily related to known central nervous system effects of dronabinol. These data support long-term, safe use of dronabinol for anorexia associated with weight loss in patients with AIDS.

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.

An epidemic of disseminated Kaposis sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposis sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposis sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposis sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposis sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposis sarcoma arising in relation to the acquired immune deficiency syndrome.

9-(1,3-dihydroxy-2-propoxymethyl) guanine (Ganciclovir) in the Treatment of Cytomegalovirus Gastrointestinal Disease with the Acquired Immunodeficiency Syndrome

9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) was used to treat 41 patients (median age, 37 years) with the acquired immunodeficiency syndrome and cytomegalovirus gastrointestinal infection. Sites of infection were the colon in 31, the esophagus in 5, the rectum in 4, and the small bowel in 1. Patients received ganciclovir, 5 mg/kg body weight, intravenously every 12 hours for 14 days. Clinical improvement was seen in 30 patients and virologic response in 32. Mainly hematologic toxicity occurred: moderate leukopenia (1000 to 1900/mm3) was seen in 7 patients and severe (less than 1000/mm3) in 1, and moderate neutropenia (500 to 1000/mm3) in 5 and severe (less than 500/mm3) in 1. A cutaneous rash developed in 2 patients. Median overall survival was 16 weeks (range, 2 to 56). Cytomegalovirus recurred in 13 patients; median time to recurrence was 9 weeks from the start of treatment. Ganciclovir may be effective in treating cytomegalovirus gastrointestinal disease in patients with the acquired immunodeficiency syndrome.

Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus type 1 (HIV-1) infection

The cases of 14 patients with thrombotic thrombocytopenic purpura admitted to one institution after 1980 were reviewed. Three of the fourteen cases occurred in patients with the acquired immunodeficiency syndrome (AIDS)-related complex and one occurred in a patient with probable human immunodeficiency virus (HIV) infection. The diagnosis in all four cases had been made after 1985. The association of thrombotic thrombocytopenic purpura with HIV infection was judged to be statistically significant on the basis of the proportion of patients with AIDS among the general population of patients admitted to the same institution during the same period. The fact that this association is only now being recognized suggests that there may be a long incubation period for thrombotic thrombocytopenic purpura or that the association is a rare one recognized now only because of the increased number of persons with AIDS.

Prognostic factors and staging classification of patients with epidemic Kaposi's sarcoma.

Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposis sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months).