Kaposi's Sarcoma In AIDS Patients Research Articles

Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway

Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma (KS), which is the most common AIDS-associated malignancy. KS is characterized by neovascularization and spindle cell proliferation. The interaction between HIV-1 and KSHV has a central role in promoting the aggressive manifestations of KS in AIDS patients; however, the pathogenesis underlying AIDS-related KS (AIDS-KS) remains unknown. Herein, we examined the potential of HIV-1 negative factor (Nef) to impact KSHV viral interleukin-6 (vIL-6)-induced angiogenesis and tumorigenesis. In vitro experiments showed that exogenous Nef penetrated vIL-6-expressing endothelial cells. Both internalized and ectopic expression of Nef in endothelial cells and fibroblasts synergized with vIL-6 to promote vascular tube formation and cell proliferation. Using a chicken chorioallantoic membrane (CAM) model, we demonstrated that Nef synergistically promotes vIL-6-induced angiogenesis and tumorigenesis. Animal experiments further showed that Nef facilitates vIL-6-induced angiogenesis and tumor formation in athymic nu/nu mice. Mechanistic studies indicated that Nef synergizes with vIL-6 to enhance angiogenesis and tumorigenesis by activating the AKT pathway in the CAM model, as well as nude mice. LY294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly impaired the ability of Nef to promote vIL-6-induced tumorigenesis in an allograft model of nude mice. Our data provide first-line evidence that Nef may contribute to the pathogenesis underlying AIDS-KS in synergy with vIL-6. These novel findings also suggest that targeting the PI3K/AKT signal may be a potentially effective therapeutic approach in AIDS-KS patients.

Non-AIDS Associated Kaposi's Sarcoma: Clinical Features and Treatment Outcome

BackgroundKaposi's sarcoma (KS) in HIV negative patients is rare and has to be distinguished from AIDS associated KS. Two groups are at risk to develop non-AIDS related KS: elderly men mainly of Mediterranean origin and persons with iatrogenic immunosuppression.Patients and MethodsIn order to define risk-groups and major clinical features we retrospectively evaluated clinical data of all patients with non-AIDS associated KS presenting to the Department of Dermatology, University Hospital Tuebingen between 1987 and 2009. Data were extracted from the tumor registry of the Comprehensive Cancer Center Tuebingen and from patient records.Results20 patients with non-AIDS KS have been identified. The average age at KS onset was 66.6 years; the male-to-female-ratio was 3∶1. Most of the patients were immigrants from Mediterranean or Eastern European countries (60%). 15 cases of classic KS versus 5 cases of iatrogenic KS were observed. In 95% of the cases, KS was limited to the skin, without mucosal, lymph node or visceral manifestation. KS lesions were in all cases multiple and mostly bilateral, the most common localization was the skin of the lower extremities. Tumor control was achieved in nearly all cases by the use of local or systemic therapy. No patient died from KS.ConclusionsUnlike KS in AIDS patients, non-AIDS associated KS is a rather localized process which rarely involves lymph nodes or organs. It is mostly seen in elderly males from Mediterranean or Eastern European countries and in most cases responsive on local or systemic therapeutic strategies.

The effect of HAART in 254 consecutive patients with AIDS-related Kaposi's sarcoma

A prospective cohort study was performed to evaluate the clinical outcomes of patients with histologically confirmed AIDS-related Kaposi's sarcoma diagnosed since the introduction of HAART. Two hundred and fifty-four consecutive patients (96% men) diagnosed with Kaposi's sarcoma between 1996 and 2008 are included. Clinicopathological and treatment details were prospectively collected. The median follow-up is over 4 years and maximum 12 years. The mean age at Kaposi's sarcoma diagnosis was 39 years and average duration of known HIV seropositivity was 4 years. At Kaposi's sarcoma diagnosis, only 19% patients were on HAART and only 7% patients had an undetectable plasma HIV viral load. Seventy-nine (31%) patients had AIDS clinical Trial Group stage T1 disease at Kaposi's sarcoma diagnosis and 122 (48%) had AIDS clinical Trial Group stage I1 disease (CD4 cell count < 150 cells/microl). Nodular grade Kaposi's sarcoma represented 28% of the tumours and was significantly associated with black African ethnicity and AIDS clinical Trial Group T1 stage disease. The overall 5-year survival is 89% (95% confidence interval 84-93). One hundred and sixty-three patients were treated with HAART alone for T0 stage Kaposi's sarcoma; only one died of Kaposi's sarcoma and only 37 (22%) required chemotherapy, giving a systemic treatment-free survival at 5 years of 74% (95% confidence interval 67-82) and the overall survival at 5 years is 91% (95% confidence interval 87-95). The high success rate of HAART in a large cohort of AIDS-Kaposi's sarcoma patients over a prolonged period of follow-up will reassure patients and clinicians that this is a well tolerated and effective approach to stage T0 Kaposi's sarcoma.

Gastrointestinal Malignancies in HIV-infected or Immunosuppressed Patients

The gastrointestinal (GI) tract is a common internal organ to be involved by human immunodeficiency virus (HIV)-related malignancies. It is the second most common site for Kaposi sarcoma after skin, and the commonest visceral site, for Kaposi sarcoma in AIDS patients. GI lymphomas have been documented in approximately 25% of AIDS patients with systemic lymphomas. Moreover, GI involvement of AIDS-lymphoma has been associated with poor prognosis and short survival. Several other malignancies that occur in the GI tract are also closely related to HIV-infected or immunosuppressed individuals; these include posttransplant lymphoproliferative disorder, Epstein-Barr virus-associated smooth muscle tumors, anal precancerous lesions, and squamous cell carcinoma. As a result of active antiretroviral therapy, patients infected with HIV are living longer and are consequently at increased risk for development of cancer. Therefore, it is possible that the number of AIDS-associated malignancies will rise and the pattern of tumors may change in the future. In this paper, the clinicopathologic features of GI malignancies associated with AIDS patients are reviewed and the differential diagnosis with other mimic lesions is discussed.

Retrospective, longitudinal analysis of serum human herpesvirus-8 viral DNA load in AIDS-related Kaposi's sarcoma patients before and after diagnosis.

Human herpesvirus 8 (HHV-8) is detected more often in patients progressing towards Kaposi's sarcoma (KS) than in patients who do not develop the disease, suggesting that the level of viremia might be associated with Kaposi's sarcoma disease and progression. Longitudinal serum samples from 19 AIDS-Kaposi's sarcoma patients, ranging from 2 years before KS till 2 years after KS diagnosis were tested. No correlation was found between viral load and progression to KS, or disease stage.

Latent and lytic HHV-8 mRNA expression in PBMCs and Kaposi's sarcoma skin biopsies of AIDS Kaposi's sarcoma patients.

Human herpes virus 8 (HHV-8) is associated with all clinical forms of Kaposi's sarcoma. HHV-8 DNA is present in Kaposi's sarcoma biopsies and is observed regularly in saliva and less consistently in blood of Kaposi's sarcoma patients. The expression pattern of latent (ORF 73) and lytic (vGCR, vBcl-2, and vIL-6) HHV-8 mRNA was studied in peripheral blood mononuclear cell (PBMC) samples and Kaposi's sarcoma skin biopsies from 11 AIDS Kaposi's sarcoma patients with four different nucleic acid sequence-based amplification (NASBA) assays. Patients were divided into groups according to the clinical stage of Kaposi's sarcoma (stage I-IV). All biopsies were positive for two or more of the mRNA measured. No clear difference could be seen in the expression pattern in the lesions of the different clinical stages. In the corresponding PBMC samples, very little or no mRNA was measurable in the patients with Kaposi's sarcoma stage I or II, whereas patients with more advanced Kaposi's sarcoma (stage III or IV) had more detectable mRNA in the PBMCs. Thus, the HHV-8 DNA load in the PBMCs increases in more advanced Kaposi's sarcoma, as does the frequency of mRNA detection in PBMCs.

Virologic and Immunologic Parameters that Predict Clinical Response of AIDS-Associated Kaposi's Sarcoma to Highly Active Antiretroviral Therapy

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Localization of human herpesvirus type 8 (HHV-8) in the Kaposi's sarcoma tissues and the semen specimens of HIV-1 infected and uninfected individuals by utilizing in situ polymerase chain reaction

Kaposi's sarcoma (KS) is a form of skin cancer, most commonly found in individuals suffering from acquired immunodeficiency syndrome, or AIDS. However, before the worldwide infection of human immunodeficiency virus (HIV), the rare occurrence of KS was confined to two distinct groups of individuals. In the Western world, the classical form of KS was often found in older men (60–70 years of age) from the Mediterranean area. Another form called endemic KS, was found in Equatorial Africa. Currently, the most common cases of KS are found in individuals suffering from AIDS. This is called AIDS-associated KS. Between 30 and 40% of male, homosexual AIDS patients suffer from AIDS-associated KS. KS is also occasionally diagnosed in transplant patients receiving immunosuppressive drugs (to keep their body from rejecting the foreign organ). As opposed to cases of classic and endemic KS, the KS in AIDS patients progresses very quickly, often with a fatal outcome. Human herpesvirus type 8 (HHV-8) has been implicated as the cause of Kaposi's sarcoma (KS), but the exact connection of the virus to the neoplasm is not known. The virus has been detected within the sarcoma skin lesions, but has additionally been seen in peripheral blood cells, semen samples, prostate tissue, and other types of soft tissue tumors. In this study, we evaluated HHV-8 within the skin lesion of KS as well as in semen specimens obtained from HIV-1 infected and uninfected specimens from HIV-1-seronegative individuals. Twenty-eight tissue samples representing AIDS-associated, endemic KS, and six non-KS patients were collected for observation from different centers throughout the world. The tissues were examined utilizing in situ polymerase chain reaction (ISPCR) and hybridization to identify and localize the herpesvirus within the KS lesions. With the use of the sensitive ISPCR technique, HHV-8 DNA was detected in the spindle cells within the nodular skin lesions, as well as in the microvascular endothelial cells which line small vessels within the lesions in all forms of KS. In addition, we analysed semen specimens from HIV-1 infected and uninfected men, our analyses revealed that HHV-8 was present in the significant proportions of the HIV-1-infected-individuals' sperm, as well as in the mononuclear cells of the semen specimens. HHV-8 DNA was demonstrated, by ISPCR, in KS lesions as well as in seminal mononuclear cells and sperm of significantly high proportion of HIV-1-infected men. What role the presence of HHV-8 in the sperm cells plays in the sexual transmission of this herpesvirus will require further study. However, the reports which demonstrate that KS lesions can develop in infants of only a few weeks of age, increases the possibility that this agent may be vertically transmitted. It can be suggested that HHV-8 is relatively ubiquitous and its frequency increases with the increasing immunosuppression.

Suspending enrollment in a two-stage phase II trial of AIDS Kaposi's Sarcoma patients

Suspending enrollment in a two-stage phase II trial of AIDS Kaposi's Sarcoma patients

Recruitment in a Two-Stage Phase II Trial of AIDS Kaposi's Sarcoma Patients

23 A phase II trial of 9-cis retinoic acid in AIDS Kaposi's Sarcoma (KS) patients was undertaken by the AIDS Malignancies Consortium (AMC), an NCl-sponsored consortium of 13 clinical centers and an operations center. To be eligible for the trial, patients had to have biopsy-proven AIDS KS without symptomatic organ involvement and been on stable antiretroviral therapy for at least 4 weeks. The objective of the trial was to test the hypothesis that the response rate is ≤ 15% against the alternative that it is ≥ 30%. Using a two-stage design, 19 patients were to be enrolled in the first stage. If at least 4 responses were observed, enrollment would continue up to a total of 55 patients. If fewer than 4 responses were observed, the study would be closed. Within three months of opening for patient accrual, a sufficient number of patients were enrolled to stop accrual while the patients were observed for response. The study re-opened three months later. Patients enrolled in the initial cohort were significantly older (mean age=42 years) than patients enrolled after the trial reopened (mean age=36 years). One of the benefits of the two-stage design is that it is possible to accomplish the trial's objectives with fewer patients than a one-stage design. There are, however, several disadvantages to temporarily halting enrollment. Recruitment in a multicenter clinical trial requires a considerable amount of effort at the clinical centers and coordination by the operations center. Suspending enrollment may diminish enthusiasm for the study and divert resources originally allocated to it. Furthermore, patients recruited when the trial reopens may not be comparable to those enrolled initially. Using a one-stage design would have required more patients, but would have been completed earlier given the rapid rate of patient accrual.

Human herpesvirus 8 in Kaposi's sarcoma and Kaposi's sarcoma-mimicking vascular tumors.

Kaposi's sarcoma (KS) had been a rare and unusual vascular tumor until a recent epidemic of a disseminated and fulminant form of KS in AIDS patients. Infectious agents have been suspected of causing KS, and recently partial genomic DNA sequences of human herpesvirus 8 (HHV8) have been identified in AIDS-associated KS lesions. Since then, genomic DNA sequences of HHV8 have been isolated in other forms of KS. Although the partial genomic DNA sequence of HHV8 was reported to be, if rare, identified in vascular tumors other than Kaposi's sarcoma (KS), the presence of HHV8 in a very large fraction of KS indicates that detection of HHV8 by PCR is a useful auxiliary tool in differentiating KS from other KS-mimicking vascular tumors. We examined whether the 233-bp segment of the viral DNA was detected in Korean patients with KS and other KS-mimicking vascular tumors. HHV8 sequences were identified in all of nine classic type of KS but not in three epithelioid hemangioendotheliomas and seven angiosarcomas. Our results confirm the relatively restricted distribution of HHV8 and also argue against the likelihood of secondary colonization of KS cells by HHV8.

Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species.

Simian retroperitoneal fibromatosis (RF) is a vascular fibroproliferative neoplasm which has many morphological and histological similarities to human Kaposi's sarcoma (KS). Like epidemic KS in AIDS patients, RF is highly associated with an immunodeficiency syndrome (simian acquired immunodeficiency syndrome [SAIDS]) caused by a retrovirus infection. Recently, a new gammaherpesvirus, called Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), has been identified in KS tumors, suggesting that KS has a viral etiology. Our previous experimental transmission studies and epidemiological data suggest that RF also has an infectious etiology. In order to determine whether a similar virus is also associated with RF, we have assayed for the presence of an unknown herpesvirus using degenerate PCR primers targeting the highly conserved DNA polymerase genes of the herpesvirus family. Here we provide DNA sequence evidence for two new herpesviruses closely related to KSHV from RF tissues of two macaque species, Macaca nemestrina and Macaca mulatta. Our data suggest that KSHV and the putative macaque herpesviruses define a new group within the subfamily Gammaherpesvirinae whose members are implicated in the pathogenesis of KS and KS-like neoplasms in different primate species.

Overview of the Management of AIDS-Related Kaposi's Sarcoma

To review the epidemiology, pathogenesis, clinical presentation, diagnosis, and staging of Kaposi's sarcoma (KS), as well as the current role of local and systemic therapies in the management of AIDS-related KS (AIDS-KS). MEDLINE and CANCERLIT searches of the English-language medical literature were conducted. Emphasis was placed on studies published since the onset of the AIDS epidemic in the early 1980s. A manual review of selected bibliographies was also completed. AIDS-KS is a disease with a heterogeneous presentation that affects approximately 20% of patients with AIDS. Although the proportion of AIDS patients developing this disease during the course of their illness is declining, the actual number of AIDS-KS cases is increasing. The etiology of AIDS-KS is not clear, but a sexually transmitted cofactor has been implicated. Recent reports demonstrate that a herpes-like virus may be responsible for the development of KS in patients with and without AIDS. Furthermore, the cellular origin of KS has not been identified and questions remain about whether KS represents a true malignancy. The system used in staging patients with AIDS-KS has changed dramatically since initial therapeutic trials were conducted; this may account for observed differences in outcome among trials. The immunologic status of patients is now included as part of the staging system, since it has prognostic significance. Since specific therapy for AIDS-KS is not curative and does not prolong survival, it should be directed at improving patient cosmesis and palliation of disease-related symptoms. Local therapy, such as radiation, cryotherapy, and intralesional chemotherapy, is recommended for the management of limited disease. Systemic interferon alfa or chemotherapy is indicated for disseminated disease. Interferon alfa is useful in patients with predominantly mucocutaneous disease and is most effective in patients with good prognostic factors, such as absence of B symptoms, no history of opportunistic infections, and a CD4 count of more than 200 cells/mm3. Interferon alfa alone or in combination with zidovudine produces responses in approximately 30% of AIDS-KS patients with good prognostic factors. Single-agent or combination chemotherapy is indicated for rapidly progressive or advanced AIDS-KS. Commonly used agents include doxorubicin, daunorubicin, bleomycin, vincristine, and vinblastine. Responses can be expected in at least 50% of patients treated with single-agent or combination chemotherapy. However, many patients are unable to tolerate the toxicity associated with systemic AIDS-KS therapy. Future research will focus on therapies that target the underlying pathogenesis of this disease. The optimal therapy for patients with AIDS-KS has not been determined. Treatment is appropriately directed at palliation of disease-related symptoms as no therapy has been unequivocally proven to impact survival. Local therapies should be used in the management of localized disease, while systemic therapy is appropriate for disseminated disease. Interferon alfa is useful in patients with primarily mucocutaneous disease or asymptomatic visceral involvement. Chemotherapy is indicated in patients who have rapidly progressive or advanced disease. Therapy must be individualized according to the patient's disease course and other patient-specific factors.

Diffuse Bilateral Lung Uptake of TI-201 Chloride in CMV Pneumonitis

Diffuse intense lung uptake of TI-201 chloride without abnormal Ga-67 citrate in a case of cytomegalovirus pneumonitis in a patient with AIDS is presented. An autopsy performed within 4 days of imaging revealed no pulmonary pathology other than diffuse cytomegalovirus infection with abundant histiocytes and inclusion bodies and pulmonary congestive heart failure. Among the various mechanisms of TI-201 accumulation, active transport through Na-K ATPase appears to be predominant in this case, as suggested by innumerable histiocytes. It is the authors' experience that positive TI-201 uptake without abnormal Ga-67 accumulation is highly specific for pulmonary Kaposi sarcoma. The presence of such discrepancy between TI-201 and Ga-67 uptake in AIDS patients decreases the specificity of a TI-201 positive/Ga-67 negative lesion for pulmonary Kaposi sarcoma, especially with the rising incidence of both cytomegalovirus and Kaposi sarcoma in AIDS patients.

Periportal contrast enhancement on CT scans of the liver.

Periportal contrast enhancement relative to adjacent liver and portal blood has been reported on CT scans in cases of schistosomiasis and hepatic Kaposi sarcoma in AIDS patients. We observed this phenomenon in 10 (8%) of 130 consecutive, contrast-enhanced, nondynamic CT examinations of the abdomen. Thus, the occurrence is more common and less specific than previously reported. Seven of the 10 patients in our series were receiving chemotherapy for malignant disease, and three had abdominal pain with no definitive diagnosis. In four of the 10 patients, corresponding areas of periportal low attenuation or radiolucency were observed on initial dynamically enhanced scans. Periportal enhancement may be related to late diffusion of contrast material into periportal areas that were initially radiolucent. Such diffusion may occur because of endothelial insult. Periportal contrast enhancement appears to be a nonspecific finding on nondynamic contrast-enhanced CT scans of the abdomen. Periportal enhancement is important to recognize because it can mimic the appearance of portal vein thrombosis and may also be used to differentiate intrahepatic biliary dilatation from periportal radiolucency.

AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposi sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients.

Pulmonary disease in the acquired immune deficiency syndrome.

T he acquired immunodeficiency syndrome (AIDS) is the most recent addition to the long list of primary and secondary immune deficiencies. Unfortunately, it has rapidly become the most common immune deficiency diagnosed in the United States today. Between the first report in 1981 and early 1984, over 3,000 cases of AIDS were recorded by the Centers for Disease Control.’ This article reviews the major features of the immune deficiency in AIDS, as well as the diagnosis and treatment of pulmonary manifestations occurring in the setting of this newest immune deficiency state. AIDS is defined by the Centers for Disease Control as the occurrence of a disease indicative of underlying cellular immune deficiency in persons without prior history of immunologic abnormality. The most common diseases which fit this definition are Kaposi’s sarcoma before age 60, Pneumocystis carinii pneumonia, and one or more other serious opportunistic infections. Pneumocystis pneumonia is the presenting manifestation in over 50 percent of AIDS cases.2 The overall case-fatality rate for AIDS is approximately 40 percent; however, the two-year mortality for patients who have experienced one or more opportunistic infections is in excess of 90 percent.2 While most cases have occurred in the United States, many cases have been reported from Western Europe, mostly in homosexual and bisexual males with the past history of sexual contacts from the United States. In addition, cases of AIDS are being reported with increasing frequency among heterosexual males and females in Haiti and Zaire. Groups recognized to be at increased risk include homosexual and bisexual males, intravenous (IV) drug users, hemophiliacs, Haitian immigrants, and sexual contacts of the above groups. The nature of the groups recognized to have an increased risk for developing AIDS suggests strongly that this immune deficiency has an infectious etiology. The available epidemiologic evidence points to an infectious agent transmissible by sexual contact, shared needle use, or blood. The putative AIDS agent has not been identified to date, recent studies point to involvement of double-stranded RNA viruses (retroviruses) of which the human T cell leukemia virus is the prototype of man.3 In view of its probable viral etiology, AIDS should be classified as a secondary immune deficiency. Patients with AIDS may have Pneumocystis pneumonia, Kaposi’s sarcoma, or other serious opportunistic infections. Fever of unknown origin (FUO) associated with diarrhea and 9-kg weight loss is a common presenting syndrome. In many patients with FUO, thrush or Pneumocystis develops within several weeks or months. It is well recognized that patients with AIDS who have Kaposi’s sarcoma often subsequently have opportunistic infections. Thus, a high index of suspicion for Pneumocystis pneumonia is warranted in AIDS-Kaposi sarcoma patients in whom cough and dyspnea develop. Another syndrome designated as the lymphadenopathy syndrome or AIDS-related complex (ARC) has recently been identified in the same population groups at increased risk for AIDS . Most patients are homosexual or bisexual males with chronic lymphadenopathy, sometimes associated with low-grade fevers and night sweats. Mild to moderate immunologic abnormalities are usually present, linking the syndrome with AIDS. It is clear that some patients with the ARC syndrome have progressed to AIDS during prospective follow-up; however, the true incidence of such progression will require many years of study. Two other illnesses that appear to be related to AIDS include idiopathic thrombocytopenic purpura (ITP) in young males,6 non-Hodgkin’s lymphoma, and possibly Hodgkin’s disease. Numerous functional and phenotypic abnormalities of the immune system are found in AIDS. The most significant defects involve cell-mediated immunity as evidenced by the spectrum of viral, fungal, protozoan, and mycobacterial infections. The most characteristic feature in established AIDS is depletion of helper T cells, as enumerated with the monoclonal antibodies OKT4 or Leu 3 47 The numbers of suppressor/cytotoxic cells are normal to increased. Elevated levels of IgG and IgA are frequently observed; however, primary antibody responses may be defective, a point

Pulmonary Disease in the Acquired Immune Deficiency Syndrome

T he acquired immunodeficiency syndrome (AIDS) is the most recent addition to the long list of primary and secondary immune deficiencies. Unfortunately, it has rapidly become the most common immune deficiency diagnosed in the United States today. Between the first report in 1981 and early 1984, over 3,000 cases of AIDS were recorded by the Centers for Disease Control.’ This article reviews the major features of the immune deficiency in AIDS, as well as the diagnosis and treatment of pulmonary manifestations occurring in the setting of this newest immune deficiency state. AIDS is defined by the Centers for Disease Control as the occurrence of a disease indicative of underlying cellular immune deficiency in persons without prior history of immunologic abnormality. The most common diseases which fit this definition are Kaposi’s sarcoma before age 60, Pneumocystis carinii pneumonia, and one or more other serious opportunistic infections. Pneumocystis pneumonia is the presenting manifestation in over 50 percent of AIDS cases.2 The overall case-fatality rate for AIDS is approximately 40 percent; however, the two-year mortality for patients who have experienced one or more opportunistic infections is in excess of 90 percent.2 While most cases have occurred in the United States, many cases have been reported from Western Europe, mostly in homosexual and bisexual males with the past history of sexual contacts from the United States. In addition, cases of AIDS are being reported with increasing frequency among heterosexual males and females in Haiti and Zaire. Groups recognized to be at increased risk include homosexual and bisexual males, intravenous (IV) drug users, hemophiliacs, Haitian immigrants, and sexual contacts of the above groups. The nature of the groups recognized to have an increased risk for developing AIDS suggests strongly that this immune deficiency has an infectious etiology. The available epidemiologic evidence points to an infectious agent transmissible by sexual contact, shared needle use, or blood. The putative AIDS agent has not been identified to date, recent studies point to involvement of double-stranded RNA viruses (retroviruses) of which the human T cell leukemia virus is the prototype of man.3 In view of its probable viral etiology, AIDS should be classified as a secondary immune deficiency. Patients with AIDS may have Pneumocystis pneumonia, Kaposi’s sarcoma, or other serious opportunistic infections. Fever of unknown origin (FUO) associated with diarrhea and 9-kg weight loss is a common presenting syndrome. In many patients with FUO, thrush or Pneumocystis develops within several weeks or months. It is well recognized that patients with AIDS who have Kaposi’s sarcoma often subsequently have opportunistic infections. Thus, a high index of suspicion for Pneumocystis pneumonia is warranted in AIDS-Kaposi sarcoma patients in whom cough and dyspnea develop. Another syndrome designated as the lymphadenopathy syndrome or AIDS-related complex (ARC) has recently been identified in the same population groups at increased risk for AIDS . Most patients are homosexual or bisexual males with chronic lymphadenopathy, sometimes associated with low-grade fevers and night sweats. Mild to moderate immunologic abnormalities are usually present, linking the syndrome with AIDS. It is clear that some patients with the ARC syndrome have progressed to AIDS during prospective follow-up; however, the true incidence of such progression will require many years of study. Two other illnesses that appear to be related to AIDS include idiopathic thrombocytopenic purpura (ITP) in young males,6 non-Hodgkin’s lymphoma, and possibly Hodgkin’s disease. Numerous functional and phenotypic abnormalities of the immune system are found in AIDS. The most significant defects involve cell-mediated immunity as evidenced by the spectrum of viral, fungal, protozoan, and mycobacterial infections. The most characteristic feature in established AIDS is depletion of helper T cells, as enumerated with the monoclonal antibodies OKT4 or Leu 3 47 The numbers of suppressor/cytotoxic cells are normal to increased. Elevated levels of IgG and IgA are frequently observed; however, primary antibody responses may be defective, a point