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Introduction Individuals with HIV infection and cancer are faced with two complex life-threatening diseases. Treatment of such complex illnesses is more straight-forward for the clinician when adequate evidence-based clinical guidelines [...]

* Objective: To determine the clinical significance of cytomegalovirus (CMV) blood and urine cultures in patients with human immunodeficiency virus (HIV) infection. * Design: Inception cohort of patients with HIV infection and CMV culture data. * Setting: Government referral-based research hospital. * Patients: A total of 322 HIV-infected patients who had a CMV blood culture and 293 HIV-infected patients who had a CMV urine culture within 7 days of a CD4 determination. * Measurements: Cytomegalovirus blood and urine culture results; circulating CD4 lymphocyte counts; pathologic or retinopathic findings of CMV disease. * Results: Nine of 26 patients (34.6%) with CMV viremia subsequently developed CMV end-organ disease compared with 11 of 74 (14.9%) patients without viremia, (difference, 19.7%; 95% CI, -0.3% to 39.7%). Fifteen of 47 patients (31.9%) with CMV viruria developed end-organ disease compared with 4 of 43 (9.3%) patients without viruria, (difference, 22.6%; CI, 6.7% to 38.5%). Cytomegalovirus culture positivity had poor predictive value for the subsequent development of end-organ disease (35% for viremia and 28% for viruria). Further, patients with proven end-organ disease were often not viremic (45%), but most were viruric (88%). Cytomegalovirus viremia did not correlate with the presence of either fever or weight loss in this patient group. Both blood culture positivity and urine culture positivity varied inversely with the CD4 count (P = 0.0001 for both associations). * Conclusions: The likelihood that a blood or urine culture will be positive in a patient with HIV infection correlates better with immunologic status than with current or future clinical status. Although the absence of CMV viruria may suggest that CMV disease is not present, CMV blood and urine cultures have poor diagnostic and predictive value and therefore should be used primarily for research purposes or drug susceptibility testing and not for making clinical decisions., HIV-infected individuals who have a positive blood or urine culture for cytomegalovirus (CMV) may not be more likely to develop CMV end-organ disease than those who do not. End-organ diseases often caused by CMV in HIV-positive individuals include retinitis, enteritis and pneumonitis. Among 615 HIV-infected patients, 322 underwent a blood culture for CMV and 293 underwent a urine culture for CMV. Thirty-five percent of the patients with a positive blood culture for CMV subsequently developed CMV end-stage disease. Thirty-two percent of the patients with a positive urine culture developed CMV end-organ disease. Of the 29 patients who underwent a blood or urine test within seven days of developing CMV end-organ disease, 55% had a positive blood culture for CMV and 88% had a positive urine culture for CMV. A positive blood culture for CMV was not associated with a fever or weight loss among these patients.

Patients with HIV (human immunodeficiency virus) infections have a high risk of developing other life-threatening infections. Patients with severe HIV infections should be treated with drugs to prevent an infection with Pneumocystis carinii (P. carinii), a fungus that causes pneumonia. Pentamidine and trimethoprim/sulfamethoxazole have been shown to be effective in treating pneumonia caused by P. carinii. However, it has been reported that treatment with pentamidine in the form of an aerosol reduces the sensitivity of medical procedures used to diagnose pneumonia. The method of choice for diagnosing P. carinii pneumonia in patients with HIV is to examine a sample of sputum (mucus coughed up from the lungs). This article describes the results of a study designed to evaluate the effect of treatment with aerosol pentamidine on the diagnosis of pneumonia in patients with HIV. A total of 348 sputum samples from patients with HIV were examined, 193 from patients treated prophylactically with pentamidine, 29 from patients treated with other drugs and 126 from patients not receiving drug therapy. Fifty-four of the 72 cases of pneumonia found were diagnosed using the sputum samples. Forty-four of the cases of pneumonia occurred in patients not receiving drug therapy and 28 of the cases occurred in patients treated with pentamidine. Treatment with pentamidine reduced the diagnostic sensitivity of the induced sputum test by 28 percent (from 92 percent to 64 percent). Despite the reduction in sensitivity, it is concluded the induced sputum test should remain the first test used to diagnose P. carinii pneumonia in patients with HIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

In patients with the acquired immunodeficiency syndrome (AIDS), the depletion of a certain subtype of white blood cell known as CD4 lymphocytes, has been associated with worsening of the disease. CD4 lymphocytes are measured by number of cells per cubic millimeter of blood (cells/mm3). Greater than 200 CD4 cells/mm3 implies a reasonably functional immune system, while counts of less than 50 cells/mm3 indicate that severe disease and death are likely to be imminent. A group of patients receiving zidovudine, which retards the rate of AIDS progression, was also monitored for CD4 cell levels. Of the 55 patients studied over 5 years, 44 had died, 10 were alive, and the status of 1 was unknown. Among the 44 patients who had died, 41 had their levels of CD4 cells measured in the six months before their deaths. In 40 of these patients, CD4 cells had fallen to less than 50/mm3. While declining CD4 levels are predictive of death in the near future, many of the patients with CD4 counts of less than 50/mm3 lived several months. Furthermore, CD4 counts of greater than 50 cells/mm3 are not protective against the infections that AIDS patients experience. However, falling CD4 levels do imply a very poor prognosis. While a cure for AIDS is not imminent, therapeutic strategies that maintain CD4 counts at greater than 50 cells/mm3 might improve long-term survival considerably. (Consumer Summary produced by Reliance Medical Information, Inc.)

There are many issues pertaining to the implementation of combination drug therapies for HIV infection. Studies which may determine the effectiveness of a drug or its possible toxicity are done using tissue cultures (in the laboratory) do not necessarily reflect the effects of the drugs in the human body. Animal models yield important data that are applicable to drug doses in humans. End points which determine the effectiveness of a drug in a clinical trial are critical in this research. But if the end points are aspects of disease progression, the answers will take decades to develop. In a fatal disease, such as AIDS, this is unacceptable. There is a need to establish other reliable end points, such as laboratory markers. However, there are problems with the use of laboratory markers, such as the levels of the viral protein p24, as end points. Some end points may show a synergistic effect of a combination of drugs, while others may show additive effects, and others, no effect. Testing of the validity of the use of laboratory markers must be incorporated into clinical trials. If the toxicity levels are determined for single drugs, it is felt that this does not have to be re-established for their use in combination clinical trials. Animal models could answer questions such as this, very rapidly. With increasing numbers of drugs available with activity against HIV, animal studies are important to establish which combinations work best and which should be tested in clinical trials. (Consumer Summary produced by Reliance Medical Information, Inc.)

Zidovudine (ZDV, which is the same as AZT) has been found to prolong the life of patients with AIDS or AIDS-related complex (ARC). In preliminary studies, two other drugs, 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), have shown signs of being effective. However, there are limitations to the use of the available therapies, such as the toxicity occurring with long-term use. The human immunodeficiency virus (HIV) has been shown to become resistant to ZDV after approximately one year of treatment. It appears unlikely that a single drug will be the sole treatment for HIV infection or AIDS, and rather that a combination of various therapies will have to be used. Combination therapy involves either treatment with multiple drugs at the same time, or alternating or intermittent use of the drugs. Certain combinations of drugs which work against HIV appear to be synergistic (they have greater activity when used together than if their effects were just added together). This is important if the toxicity of the drugs is just additive. A combination of drugs can be used which affects the virus at different stages of replication and multiplication. An ideal combination of drugs is one that has synergistic activity against the virus and is antagonistic to toxicity (the combination of drugs is less toxic than the two drugs individually). Certain drugs may counteract the toxicities of other drugs. For example, cellular cytokines such as erythropoietin counteract the toxic effects of ZDV on bone marrow cells. If drugs have different toxicities, the intermittent or alternating use of the drugs may be beneficial. Combination therapy may also prevent or delay the virus from becoming resistant to the drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

The acquired immunodeficiency syndrome (AIDS) reduces the function of the immune system, thereby making the patient vulnerable to life-threatening infections. Soon after AIDS was discovered, it was observed that some AIDS patients developed a type of cancer called non-Hodgkin lymphoma, and since then its occurrence in AIDS patients has been increasing steadily. Non-Hodgkin lymphoma is a cancer involving the lymph nodes of the body which may affect the brain. This study assessed the incidence of non-Hodgkin lymphoma in 55 patients with AIDS or AIDS-related complex (ARC) who were receiving antiretroviral drugs. The subjects were being treated with either AZT (azidothymidine) or zidovudine-containing regimens. Eight of the 55 patients (14.5 percent) developed non-Hodgkin lymphoma of the B-cell type an average of 24 months after starting antiretroviral treatment. It was estimated that AIDS patients being treated with antiretroviral drugs have a 29 percent chance of developing lymphoma after 30 months of therapy and a 46 percent chance after 36 months of therapy. It is concluded that AIDS patients being treated with antiretroviral drugs who survive for as long as three years on these drugs have a relatively high chance of developing non-Hodgkin lymphoma. It is possible that the antiretroviral treatment that prolongs life allows the lymphoma to occur at a higher rate, but more research will be needed to determine if this is in fact the mechanism behind the occurrence of the cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

AIDS is caused by infection with the human immunodeficiency virus (HIV), which replicates within immune cells, particularly monocytes/macrophage and helper T cells. HIV replication can be prevented by antiviral agents, which act at various sites in the life cycle of HIV. For example, the antiviral agent zidovudine inhibits the enzyme reverse transcriptase, which is involved in the replication of the virus. Combined regimens of antiviral agents may be more effective in treating HIV infection because the development of viral strains that are resistant to both antiviral agents is less likely. Also, antiviral activity may be increased and drug toxicity may be reduced with combination therapy. After the virus is controlled, treatment may be started to enhance the immune responses and repair immune damage. The possible sites in the life cycle of HIV where drugs can act to prevent viral replication are described, and include cell binding and entry; replication, latency, and reactivation; and protein production and assembly. The anti-HIV activity of the drugs 2',3'-dideoxynucleosides and zidovudine are reviewed. The antiviral agent 2',3'-dideoxycytidine prevents HIV replication, but causes dose-dependent peripheral neuropathy (disease of the peripheral nervous system). Zidovudine, developed 26 years ago, is a powerful inhibitor of HIV replication, and protects immune T cells from destruction by HIV. Clinical trials show that zidovudine produces clinical, immunologic, and virologic benefits in patients with severe HIV infection. Although zidovudine can cause serious toxic effects in the bone marrow, it is not toxic to the heart, kidney, and liver. Zidovudine can improve HIV-related dementias in adults and decreased cognitive function in children. The toxicity of these drugs can be reduced by drug-free rest periods and alternating regimens. (Consumer Summary produced by Reliance Medical Information, Inc.)

The reverse transcriptase inhibitor 2',3'-dideoxycytidine (ddC) is capable of mediating virologic and immunologic improvements in some patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. However severe peripheral neuropathy often develops as a dose-limiting toxicity in ddc-treated patients. Lower doses of ddC may avoid this side effect, while retaining antiviral activity associated with this drug. A series of clinical trials is currently examining regimens employing simultaneous or alternating administration of ddC and 3'-azido-3'-deoxythymidine (zidovudine). Concurrent therapy with more than one drug may allow the use of decreased drug doses and thus reduce dose-dependent toxicities, whereas alternating schedules would provide rest periods from each drug without interrupting therapy. Since zidovudine and ddC possess different toxicity profiles and zidovudine-resistant strains remain susceptible to ddC in vitro, such regimens could theoretically provide additional benefits and reduced toxicity, compared with either agent administered alone. It is hoped that these ongoing and future studies will uncover new and better ways to exploit the therapeutic potential of ddC. However, at present, ddC is an experimental drug and should not be used outside the setting of an approved clinical protocol., Researchers have discovered that HIV, the virus which causes AIDS, can be suppressed by agents that inhibit the viral enzyme known as reverse transcriptase; this enzyme is essential for the replication of HIV in the body. The dideoxynucleosides, zidovudine (AZT) and 2',3'-dideoxycytidine (ddC), inhibit the enzyme reverse transcriptase, and are therefore effective against HIV-1 infection. However, AZT treatment is associated with development of myelosuppression (inhibition of bone marrow function) which leads to blood disorders. Its use has also stimulated the development of AZT-resistant strains of HIV. Treatment with ddC has been associated with the occurrence of severe peripheral neuropathy, or nerve disease, which worsens with increasing doses of ddC. Using low doses of ddC reduces the incidence of adverse drug effects, but these doses remain effective at decreasing the levels of p24 antigen, a marker for HIV disease. Reduced ddC doses also remain effective at increasing the numbers of CD4+ lymphocytes, which are immune cells that are particularly vulnerable to destruction by HIV. Simultaneous treatment with both ddC and AZT allows the use of lower doses of each drug, resulting in a reduced incidence of toxic side effects. Drug regimens which alternate the use of AZT with ddC provide rest periods from each drug without interrupting anti-HIV treatment. Because AZT and ddC cause different toxicities, simultaneous and alternating regimens of ddC combined with AZT may be effective against HIV disease without causing adverse drug reactions. Clinical trials with human subjects are currently underway to test the effectiveness and safety of combined treatment with AZT and ddC in a simultaneous or alternating regimen. However, ddC is still an experimental drug and should not be used without clinical supervision. (Consumer Summary produced by Reliance Medical Information, Inc.)

Opportunistic infections, which occur because of a patient's altered physiological state, are the major cause of life-threatening disease and death in patients infected with the human immunodeficiency virus (HIV). HIV infection depletes CD4 or helper T cells, a type of immune cell involved in increasing the production of antibodies, immune proteins that bind to and inactivate foreign particles. The depletion of CD4 cells results in a weakened immune system and increased risk of developing opportunistic infections. The number of CD4 cells has been shown to be a good indicator of the immune activity in HIV-infected patients, and have been used to predict whether an HIV-infected patients will develop AIDS (acquired immunodeficiency syndrome). The usefulness of CD4 counts in diagnosing pneumonia in 100 HIV-infected patients was assessed. CD4 counts were less than 200 cells per cubic millimeter before 46 of 49 cases of pneumocystis pneumonia, before all eight cases of cytomegalovirus pneumonia, all seven cases of Mycobacterium avium-intracellular infection, and 19 of 21 cases of infection with Cryptococcus neoformans. Thus, pneumocystis pneumonia, cytomegalovirus pneumonia, and lung infection by C. neoformans and M. avium-intracellular are not likely to occur in patients with CD4 counts greater than 200 to 250 cells per cubic millimeter, or a CD4 percent of circulating lymphocytes of 20 to 25 percent. Patients with CD4 counts less than 200 cells per cubic millimeter may benefit from prophylaxis against pneumocystis infection. (Consumer Summary produced by Reliance Medical Information, Inc.)

The human immunodeficiency virus (HIV) is considered to be the cause of acquired immunodeficiency syndrome (AIDS). There is no cure for AIDS and treatment given to patients with this disease can merely slow the progress of the disease. Zidovudine (AZT) has been the most effective treatment thus far. However, the side effect of bone marrow toxicity has limited its usefulness with some patients. Another drug that has recently been used is 2',3'-dideoxycytidine (ddC), which can cause lesions of the skin and mucus membranes. This drug has exhibited inhibitory effects in test tubes upon HIV-infected helper T cell replication. The skin reaction associated with this drug was examined in 20 men with AIDS or AIDS-related complex. All patients were monitored; two cases are discussed in some detail. Fourteen (70 percent) of the patients with HIV infection developed a mucocutaneous reaction within 10 to 11 days of treatment with ddC. Other complications associated with this drug included systemic symptoms and oral ulcers which developed within four to six days of the treatment in nine patients. A correlation was observed between higher dosages of the drug and the occurrence of skin and oral lesions. In more than 60 percent of the affected patients, the symptoms were transient and disappeared, even when treatment was not stopped. Very mild or no side effects were observed in patients given low doses of ddC.