Integrating cannabis into clinical cancer care.

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.

Cannabis in cancer care.

Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.

Treatment options in zidovudine intolerance or failure.

AIM: To compare the efficacy and safety of didanosine and zalcitabine in patients who could not tolerate zidovudine or who had failed to respond adequately. PATIENTS AND METHODS: A multicentre, randomly allocated, open-label clinical trial was set up with 230 patients treated with didanosine and 237 treated with zalcitabine. All had previously been treated unsuccessfully with zidovudine. The patients were followed for at least 1 year, with an average of 16 months. RESULTS: Disease progression or death occurred in 157 patients taking didanosine and 152 taking zalcitabine. There appeared to be a slight trend in favour of survival in the latter group. CONCLUSIONS: There is an urgent need for more effective and better tolerated antiretroviral agents in the treatment of HIV infection. Zalcitabine is at least as effective as didanosine and may provide a survival advantage in patients treated unsuccessfully with zidovudine.

Kaposi's sarcoma and central nervous system disease: a real association or an artifact of the control group? Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To test the hypothesis that Kaposi's sarcoma (KS) protects against four central nervous system (CNS) diseases in HIV-1-infected individuals. STUDY POPULATION AND DESIGN: The study population of 9404 subjects included participants in Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) protocols who were enrolled between September 1990 and September 1998. This was an observational study. METHODS: Proportional hazards regression was used to estimate adjusted relative risks for predictors of four central nervous system diseases. Covariates included occurrence of Kaposi's sarcoma, occurrence of other opportunistic infections or malignancies, baseline CD4+ count, and other baseline characteristics. RESULTS: Among the 5944 participants without progression to AIDS at entry, 451 developed a CNS disease. The adjusted relative risk of any CNS disease for those who developed Kaposi's sarcoma versus those who did not develop any AIDS-defining event was 1.41 [95% confidence interval (CI), 0.98-2.03; P = 0.06]. In contrast, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.37 (95% CI, 0.24-0.57; P < 0.0001). Among the 3460 participants with progression to AIDS at entry, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.71 (95% CI, 0.40-1.25; P = 0.23). CONCLUSIONS: Our analyses indicate that the risk of CNS disease associated with Kaposi's sarcoma depends strongly on the reference or control group chosen. When compared to individuals with other non-Kaposi's sarcoma AIDS-defining diseases, Kaposi's sarcoma is associated with a lower risk of CNS disease in HIV-1 positive individuals. However, when compared to individuals with no AIDS-defining disease or with a similarly mild AIDS-defining disease such as invasive candidiasis, Kaposi's sarcoma is associated with an equivalent risk of CNS disease.

A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) with expert advice in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors. DESIGN: Prospective randomized controlled trial. SETTING: Multicenter community-based clinical trials network. PATIENTS: One-hundred and fifty-three HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at least 16 weeks of combination antiretroviral therapy. INTERVENTIONS: Randomization was either to a GART group, where genotype interpretation and suggested regimens were provided to clinicians, or to a no-GART group, where treatment choices were made without such input. MAIN OUTCOMES MEASURES: Plasma HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks following randomization. The primary endpoint was change in HIV-1 RNA levels from baseline to the average of the 4 and 8 week levels. RESULTS: The average baseline CD4 cell count was 230 x 10(6) cells/l and the median HIV-1 RNA was 28,085 copies/ml. At entry, 82 patients were failing on regimens containing indinavir, 51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at 4 and 8 weeks, decreased by 1.19 log10 for the 78 GART patients and -0.61 log10 for the 75 no-GART patients (treatment difference: -0.53 log, 95% confidence interval, -0.77 to -0.29; P = 0.00001). Overall, the best virologic responses occurred in patients who received three or more drugs to which their HIV-1 appeared to be susceptible. CONCLUSION: In patients failing triple drug therapy, GART with expert advice was superior to no-GART as measured by short-term viral load responses.

A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics and private practice offices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome measures were confirmed CMV retinal or gastrointestinal mucosal disease, and death. The study enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. RESULTS: At study completion (15 months median follow-up), CMV event rates in the oral GCV and control groups were 13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment effect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically different (P = 0.0006). CONCLUSIONS: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestion of a death-rate reduction. Furthermore, results suggest that oral GVC decreased risk of CMV disease in patients not prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death endpoint, a combined analysis of studies indicated significant reduction in death rate.

Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population-based survey.

We prospectively studied 40 hospitalized patients who had well-established diagnoses of acquired immunodeficiency syndrome. Patients with confounding risk factors for neuropathy were excluded; none of the study patients had known vitamin deficiency, alcoholism, or any metabolic, drug, or toxic factor. Clinical and electrophysiologic evidence of a distal symmetric polyneuropathy was found in 35% (13/37) of the patients. Symptoms and signs of neuropathy were usually mild, and painful dysesthesias were uncommon. Amplitude reduction of sural nerve action potentials distinguished all patients with from those without clinical neuropathy. Results of other electrophysiologic studies of sural, peroneal, and median nerves were typically normal. These results provide evidence of distal axonal degeneration. Neuropathy occurred only in patients with systemic illness longer than five months' duration. When compared with patients without neuropathy, these patients had more severe weight loss and a higher incidence of clinical dementia. Follow-up evaluation showed no evidence of clinical progression over a six-month period. The pathogenesis of this common distal axonal polyneuropathy is unknown and warrants further investigation.

The relationship between Kaposi's sarcoma and intestinal parasites among homosexual males in the United States.

An interesting temporal relationship exists between the emergence of the epidemic of intestinal parasites in the homosexual male population and the subsequent appearance of Kaposi's sarcoma. Existent models suggest possible links between chronic parasitosis, viral infection, and the emergence of malignant disease. Patients with AIDS-related conditions have been demonstrated to have a high rate of asymptomatic amebiasis. Possible links between intestinal parasites and the development of Kaposi's sarcoma in human immunodeficiency virus-infected patients are explored.

Effects of the use of AZT on the medical care costs of persons with AIDS in the first 12 months.

It is important in planning to meet resource needs and financing of care of people with acquired immune deficiency syndrome (AIDS) to determine the effect of the use of azidothymidine (AZT) on overall medical care costs. This study compares the medical care costs of people with AIDS (PWAs) who received AZT with those of PWAs not receiving it. Seven of the nine PWAs who were on the AZT arm of the phase II drug trial of AZT at San Francisco General Hospital (SFGH) in 1986 and a matched sample of PWAs at SFGH who were eligible for the trial but did not participate in it were included in the study and followed for 12 months. It was found that costs in the first 12 months and especially in the first 6 months were lower for persons using AZT, primarily because of significantly lower use of hospital services. However, costs began to rise in the second 6 months for those using AZT. The authors therefore doubt that the lifetime costs of PWAs are lowered by the use of AZT and conclude that they are likely to be the same as those of PWAs not using the drug. If this is indeed the case, the use of the drug is likely to be relatively cost-effective.

Risk factors for rapid progression from hairy leukoplakia to AIDS: a nested case-control study.

To determine risk factors for early progression from oral hairy leukoplakia to AIDS, this case-control study compared 27 patients who had not progressed to AIDS within 1,000 days of diagnosis of hairy leukoplakia with 28 patients who progressed rapidly. The risk factors that proved most predictive fell into two categories: (a) those reflecting sexual practices that correlated with how early in the epidemic patients were likely to have been infected, and (b) those reflecting immune competence. Hepatitis B was associated with a fourfold risk for early progression and syphilis with a nearly threefold risk. Skin test anergy for Candida species was strikingly predictive: all of 17 tested in the early progression group were anergic, compared with only two of 12 tested in the late progression group. Although skin testing has been largely supplanted by assessment of T-cell subsets, Candida species skin testing may be of particular prognostic value in otherwise apparently healthy HIV-infected persons.

The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection.

To determine the utility of bone marrow examination for the diagnosis of opportunistic infections and lymphoma in patients with known or suspected human immunodeficiency virus (HIV) infection, we retrospectively reviewed the medical and laboratory records of all patients undergoing diagnostic bone marrow examinations at San Francisco General Hospital between January 1, 1988 and December 31, 1989. All marrow examinations of patients with known or suspected HIV infection in which specimens were examined histopathologically and/or microbiologically for opportunistic pathogens or lymphoma were analyzed. Bone marrow examination resulted in the diagnosis of mycobacterial infection in 16% of the patients studied. Blood culture was 77% sensitive and bone marrow culture was 86% sensitive for detecting disseminated mycobacterial infection. This difference was not statistically significant (p greater than 0.05). Disseminated fungal infections occurred in less than 5% of the patients studied, and most were rapidly and accurately detected by examination of stained bone marrow samples. No case of lymphoma was diagnosed by bone marrow examination. Bone marrow examination may be useful for diagnosing opportunistic infections in patients with HIV infection. Mycobacterial blood cultures have a sensitivity comparable to bone marrow cultures in detecting disseminated mycobacterial infections, are less invasive, and may be less costly. Marrow examination is not useful for diagnosing lymphoma but can determine the extent of lymphoma that has been diagnosed by other means.

Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi's sarcoma: a randomized, double-blind trial.

The effect of recombinant tumor necrosis factor-alpha (rTNF), injected directly into the tumor, was evaluated in a Phase I/II study of 27 patients with AIDS-associated Kaposi's sarcoma (KS). The maximally tolerated intralesional dose was less than 100 micrograms/m2 and the recommended intralesional dose was 25 micrograms/m2. In a double-blind, randomized, placebo-controlled study, rTNF reduced the cross-sectional area of 15 of 16 (94%) of the injected KS lesions and caused complete disappearance of 3 of 16 (19%) lesions. Only injected lesions showed a response. Rigors and fever were common dose-dependent side effects and were attenuated by meperidine. There were no changes in human immunodeficiency virus (HIV) activity as determined by serum p24 antigen levels. While biologically active, the systemic toxicity of rTNF as well as the lack of distant antitumor effects in noninjected lesions limits its clinical usefulness under the conditions employed in this trial.

Acquired immunodeficiency syndrome and related malignancies: a topical overview.

As we enter the second decade of confronting human immunodeficiency virus (HIV)-induced disease, progress in the prophylaxis and treatment of acquired immunodeficiency syndrome (AIDS)-related opportunistic infections is encouraging. While the infectious manifestations of HIV become more manageable, AIDS-related malignancies remain problematic. In the era of infection prophylaxis and antiretroviral therapy, the incidence of Kaposi's sarcoma (KS) and aggressive non-Hodgkin's lymphoma (NHL) appears to be increasing. Mounting evidence suggests that KS may result from infection with an as yet unidentified sexually transmitted agent. The increase in NHL cases may result from patients surviving longer with severe immune compromise with a possible contribution of antiretroviral therapy itself. Despite effective cosmetic treatments, survival in recently diagnosed KS patients is actually shorter than patients diagnosed with KS earlier in the epidemic. The addition of growth factors to the chemotherapeutic regimen of patients with AIDS-related NHL has not yet been translated into a survival advantage. In vitro antiviral activity and clinical evidence of possible synergy with other antiretrovirals suggests that continued investigation of alpha-interferon in treatment of AIDS-related malignancies is a priority for the second decade of challenging AIDS.

Alpha interferon therapy of AIDS-associated Kaposi's sarcoma.

Alpha interferon has been the most widely studied biologic response modifier for the treatment of Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS). At San Francisco General Hospital's AIDS Clinic, three sequential trials of recombinant interferon alfa-2b (Intron A) were conducted between August 1982 and April 1984. In the first study, ten patients with early KS were randomized to receive either low-dose (1 MU/m2) subcutaneous (SC) or high-dose (50 MU/m2) intravenous (IV) treatment 5 days per week, every other week, for eight weeks. A perceived advantage of the latter regimen led to a subsequent trial in which 20 subjects received high-dose IV therapy. A 32% objective response rate was achieved, despite the fact that these patients had less favorable disease status and more constitutional symptoms than those in the first trial and had also experienced previous opportunistic infections (Ols). A final 8-week investigation evaluated the use of 30 MU/m2 three times per week in 30 subjects. Drug-related toxicity seemed more pronounced with this regimen, but overall objective responses were identical to those seen in the high-dose IV study. None of the trials produced evidence of immune reconstitution on laboratory evaluation. The patients were not protected from developing AIDS-related OI either during or following interferon therapy, although OI was diagnosed less frequently in responders, who also displayed a distinct survival advantage over those with progressive disease. These trends remained evident when the data from the three studies were pooled with those from three parallel trials conducted at the University of California, Los Angeles (UCLA). Studies evaluating the combined use of alpha interferon and chemotherapeutic agents known to be active against AIDS-related KS (such as VP-16 and vinblastine) have thus far failed to demonstrate a synergistic antitumor effect, while toxicity has increased. In light of in vitro evidence that alpha interferon suppresses the AIDS retrovirus and has clinical efficacy in KS comparable to that of cytotoxic agents, additional investigations, focusing on maximizing therapeutic potential, are warranted.

Alpha interferon therapy of AIDS-associated Kaposi's sarcoma.

Alpha interferon has been the most widely studied biologic response modifier for the treatment of Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS). At San Francisco General Hospital's AIDS Clinic, three sequential trials of recombinant interferon alfa-2b (Intron A) were conducted between August 1982 and April 1984. In the first study, ten patients with early KS were randomized to receive either low-dose (1 MU/m2) subcutaneous (SC) or high-dose (50 MU/m2) intravenous (IV) treatment 5 days per week, every other week, for eight weeks. A perceived advantage of the latter regimen led to a subsequent trial in which 20 subjects received high-dose IV therapy. A 32% objective response rate was achieved, despite the fact that these patients had less favorable disease status and more constitutional symptoms than those in the first trial and had also experienced previous opportunistic infections (OIs). A final 8-week investigation evaluated the use of 30 MU/m2 three times per week in 30 subjects. Drug-related toxicity seemed more pronounced with this regimen, but overall objective responses were identical to those seen in the high-dose IV study. None of the trials produced evidence of immune reconstitution on laboratory evaluation. The patients were not protected from developing AIDS-related OI either during or following interferon therapy, although OI was diagnosed less frequently in responders, who also displayed a distinct survival advantage over those with progressive disease. These trends remained evident when the data from the three studies were pooled with those from three parallel trials conducted at the University of California, Los Angeles (UCLA). Studies evaluating the combined use of alpha interferon and chemotherapeutic agents known to be active against AIDS-related KS (such as VP-16 and vinblastine) have thus far failed to demonstrate a synergistic antitumor effect, while toxicity has increased. In light of in vitro evidence that alpha interferon suppresses the AIDS retrovirus and has clinical efficacy in KS comparable to that of cytotoxic agents, additional investigations, focusing on maximizing therapeutic potential, are warranted.

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

Hematologic manifestations in homosexual men with Kaposi's sarcoma.

Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Lymphadenopathy: endpoint or prodrome? Update of a 24-month prospective study.

PIP: This article presents preliminary 24-month findings from a prospective study initiated in San Francisco in 1981 with the following objectives: to refine the clinical definition of the lymphadenopathy syndrome; to compare these patients to patients with Category A acquired immunodeficiency syndrome (AIDS) with regard to epidemiologic, virologic, and immunologic variables; to follow a cohort of these patients to establish the natural history of the syndrome; and to evaluate screening variables for early transformation to more malignant manifestations of AIDS. It was hypothesized that the lymph node syndrome is prodromal AIDS, and that such patients are at risk of developing Kaposi's sarcoma, lymphoma, Pneumocystis carinii pneumonia, and other opportunistic infections. 200 homosexual lymphadenopathy patients, with a mean age of 33 years, have been enrolled in the study. These men have had an average of 800 sexual partners, and have a history of past sexually transmitted diseases. The graph of the year of onset of adenopathy parallels the exponentially increasing number of new AIDS cases over the past 4 years. Systemic symptoms seen in these patients resemble those in patients with Kaposi's sarcoma and P. carinii pneumonia. 1/3 of lymphadenopathy patients give a history of antecedent flu-like illness, often with fever, diarrhea, and upper respiratory symptoms lasting for 1 week, that occurred 1-2 months before the appearance of their nodes. Involvement of inguinal and axillary nodes has been observed in 100% of patients, while 80% have enlarged posterior cervical nodes. The average patient has 10 nodal groups involved. Immunologic testing reveals a reversal of the T-lymphocyte helper:suppressor ratio (mean of 0.7), and 2/3 of patients have both decreased absolute number and percentage of helper cells with increased suppressors. 198 of these patients have remained with persistent generalized lymphadenopathy without transformation to AIDS, yielding a 1% conversion rate. It is concluded that the lymphadenopathy syndrome is a distinct new syndrome most certainly AIDS-related. Further study will reveal whether it is truly prodromal or an alternate phenotypic response to a common inciting insult.^ieng

The pre-AIDS syndromes. Asymptomatic carriers, thrombocytopenic purpura, persistent generalized lymphadenopathy, and AIDS-related complex.

With the passage of time and the refinement of laboratory techniques, the ability to recognize disease related to human immunodeficiency virus infection has improved. Currently, a number of clinical conditions can be identified as "pre-AIDS" syndromes. These include the syndrome of persistent generalized lymphadenopathy, immune thrombocytopenic purpura, the wasting syndrome, and certain predominantly neurologic presentations. All are characterized by the presence of human immunodeficiency virus infection, symptomatic illness, and a tendency to progress to a diagnosis of full-blown AIDS that appears to be ever increasing with the passage of time.