Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), malignancies accounted for less than 10% of all deaths among human immunodeficiency virus (HIV)-infected patients. This figure may have increased, and the observed types of malignant disease may have been modified, as a result of decreased occurrence of opportunistic infections, the chronicity of HIV infection, the possible oncogenic role of HIV itself, and the aging of the HIV-infected population. METHODS: All French hospital wards involved in the management of HIV infection were asked to prospectively document the deaths of HIV-infected patients in the year 2000. Underlying causes of death were defined using a standardized questionnaire. RESULTS: Of a total of 964 deaths, 269 (28%) were attributable to malignancies. Acquired immunodeficiency virus (AIDS)-related malignancies were the underlying cause of 149 deaths (15%); among these malignancies were non-Hodgkin lymphoma (n = 105 [11%]), noncerebral lymphoma (n = 78 [median CD4 count, 86 x 10(6) per liter; interquartile range [IQR], 35-231 x 10(6) per liter), and primary cerebral lymphoma (n = 27 [median CD4 count, 20 x 10(6) per liter; IQR, 4-109 x 10(6) per liter). Kaposi sarcoma was associated with 40 deaths (4%), and cervical carcinoma was associated with 5 (0.5%). Non-AIDS-related malignancies were the underlying cause of 120 deaths (13%); these non-AIDS-related malignancies included 103 solid tumors (50 respiratory tumors, 19 hepatocarcinomas, 9 digestive tumors, and 6 anal tumors; median CD4 count, 218 x 10(6) per liter; IQR, 108-380 x 10(6) per liter) and 17 hemopathies (12 Hodgkin lymphomas, 4 myeloid leukemias, and 1 myeloma; median CD4 count, 113 x 10(6) per liter; IQR, 56-286 x 10(6) per liter). Compared with patients who died of other causes, patients who died of solid tumors were more likely to be male, to smoke, to be older, and to have higher CD4 counts. CONCLUSIONS: Malignant disease has been a major cause of death among HIV-infected patients in industrialized nations since the introduction of HAART. Whereas lethal hemopathies and Kaposi sarcoma are associated with advanced immunosuppression, lethal solid tumors can occur in patients with controlled HIV infection.     

Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals

BACKGROUND: The objective of this study was to determine the rates and predictors of non-AIDS-defining cancers (NADCs) among a cohort of human immunodeficiency virus (HIV)-infected individuals. METHODS: The authors conducted a retrospective study of 4144 HIV-infected individuals who had 26,916 person-years of follow-up and who had open access to medical care at 1 of the United States military HIV clinics during the years 1988-2003. Cancer incidence rates were race specific and were adjusted for age; these were compared with national rates using logistic regression to assess predictors of NADC development. RESULTS: One hundred thirty-three NADCs were diagnosed with a rate of 980 diagnoses per 100,000 person-years. The most frequent NADCs were skin carcinomas (basal cell and squamous cell), Hodgkin disease, and anal carcinoma. The results showed that there were higher rates of melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease among the HIV-infected cohort compared with age-adjusted rates for the general United States population. Predictors of NADCs included age older than 40 years (odds ratio [OR], 12.2; P < 0.001), Caucasian/non-Hispanic race (OR, 2.1; P < 0.001), longer duration of HIV infection (OR, 1.2; P < 0.001), and a history of opportunistic infection (OR, 2.5; P < 0.001). The use of highly active antiretroviral therapy (HAART) was associated with lower rates of NADCs (OR, 0.21; P < 0.001). A low CD4 nadir or CD4 count at diagnosis (< 200 cells/mL) was not predictive of NADCs. CONCLUSIONS: The most frequent NADCs were primary skin malignancies. Melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease occurred at higher rates among HIV-infected individuals. The implementation of screening programs for these malignancies should be considered. Most risk factors for the development of NADCs are nonmodifiable; however, the use of HAART appeared to be beneficial in protecting against the development of malignant disease.     

AIDS-related cancers in the era of highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) has shown great efficacy in reducing human immunodeficiency virus levels, increasing immunity, and prolonging the survival of persons with acquired immunodeficiency syndrome (AIDS). The risk of life-threatening infections has been greatly reduced. However, the impact of HAART on the incidence of malignancy has been less clear. Published studies generally show that the risk of developing Kaposi's sarcoma declined by about two-thirds between 1994 and 1995 and from 1996 onward (considered the HAART era). Even before 1994, the risk for Kaposi's sarcoma in persons with AIDS had declined considerably and this cancer has now become relatively uncommon. The mechanism by which this decline in incidence was achieved appears to involve improved immunity. Data on the reduction in the risk for non-Hodgkin's lymphoma are mixed. Several studies conducted between 1997 and 1999 found no reduction in the risk for non-Hodgkin's lymphoma, although the most recent data (from 1997 to 1999) show a 42% decrease in risk. Even with a one-third reduction, the risk for non-Hodgkin's lymphoma remains considerably elevated. This high risk may be related to the fact that HAART therapy does not restore the immune system to normalcy. The increased lymphocyte turnover, with its accompanying risk of genetic errors, may increase the risk of developing non-Hodgkin's lymphoma. Most reports have insufficient data to analyze the impact of HAART therapy on incidence of central nervous system lymphomas, but recent data (from 1997 to 1999) showed a significant reduction in that risk. The mechanism by which this might occur is unclear because the central nervous system is an immunologic sanctuary. The relatively low incidence of other cancers in persons with AIDS makes it difficult to gauge the effect of HAART on their incidence, but to date, no significant trends have been reported for specific tumor types or for the overall risk of non-AIDS-related cancers.     

Acquired immunodeficiency syndrome-related lymphoma in the era of highly active antiretroviral therapy

The treatment and outcome of human immunodeficiency virus (HIV) infection altered dramatically in the mid-1990s with the introduction of highly active antiretroviral therapy (HAART). Highly active antiretroviral therapy, where available, has led to a dramatic decline in mortality from HIV and a decrease in the incidence of opportunistic infections and Kaposi sarcoma. This article addresses the effects that HAART has had on acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL). Metaanalysis of numerous cohort studies confirmed that the incidence of AIDS-related NHL has decreased since the advent of HAART. This decline is most marked for primary cerebral lymphomas and systemic immunoblastic lymphoma but has not been demonstrated for Burkitt lymphoma. In addition to genetic predisposing factors, age, nadir CD4 cell count, and lack of HAART therapy predict the development of NHL. The clinical presentation of AIDS-related NHL has not changed, but several institutions have reported an improvement in survival since the introduction of HAART. Moreover, HAART has been combined safely with systemic chemotherapy in the management of NHL, and this approach results in a more modest decrease in immune function than when chemotherapy is administered alone. This has led to a more aggressive approach to the management of AIDS-related NHL and response rates and overall survival durations that are approaching those seen in stage-matched high-grade lymphomas in the immunocompetent population.     

Human immunodeficiency virus-associated lung cancer in the era of highly active antiretroviral therapy

BACKGROUND:

Lung cancer is the leading cause of death among non‐acquired immunodeficiency syndrome (AIDS)‐defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era.

METHODS:

HIV‐positive patients who were diagnosed with lung cancer at the authors' institution during the HAART era (1995‐2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. The CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cutoff points (50 cells/mL, 200 cells/mL, and 500 cells/mL). Pearson correlation coefficients were estimated for each covariate studied. Survival was determined by using the Kaplan‐Meier method.

RESULTS:

Of 80 patients, 73 had nonsmall cell lung cancer. Baseline characteristics were as follows: median patient age, 52 years; male, 80%; African Americans, 84%; injection drug users, 25%; smokers, 100%; and previous exposure to antiretroviral agents, 55%. At the time of cancer diagnosis, the mean CD4 count was 304 cells/mL, and the mean viral load was 82,420 copies/mL. The latency between HIV diagnosis and lung cancer diagnosis was significantly shorter among women (4.1 years vs 7.7 years; P = .02), and 71% of patients received anticancer therapy. The 1‐year and 3‐year survival rates for stage IIIB/IV were 25% and 0%, respectively. Grade 3/4 toxicities occurred in 60% of patients who received chemoradiation versus 36% of patients who received chemotherapy. Cancer‐related survival was better for patients with CD4 counts >200 cells/mL (P = .0298) and >500 cells/mL (P = .0076).

CONCLUSIONS:

The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for patients with lung cancer who have HIV remain poor, a high CD4 count was associated with improved lung cancer‐related survival. Cancer 2012;. © 2011 American Cancer Society.     

Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy

Background  

Women infected with human immunodeficiency virus (HIV) may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV), HIV infection and Highly Active Antiretroviral Therapy (HAART) on the development of Squamous Intraepithelial lesions (SILs). Out of the 70 HIV infected women from Douala -Cameroon (Central Africa) that we included in the study, half (35) were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL).     

AIDS malignancies in the era of highly active antiretroviral therapy

The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to dramatic declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which began in the April 2002 issue, analyzes the impact of HAART on the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.     

AIDS malignancies in the era of highly active antiretroviral therapy

The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which will conclude in the May 2002 issue, analyzes the impact of HAARTon the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.     

Profile of patients with Kaposi's sarcoma in the era of highly active antiretroviral therapy.

PURPOSE: Since the advent of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) among AIDS patients has declined both nationwide and in King County, Washington. We sought to compare clinical parameters of patients diagnosed with KS in the pre-HAART (1990 to 1996) and HAART (1997 to 2002) eras. METHODS: We used patient data abstracted from the Adult/Adolescent Spectrum of HIV-Related Diseases study of Public Health-Seattle and King County. RESULTS: Patients diagnosed with KS in the HAART era (n = 40) were significantly more likely (P < .05) than pre-HAART-era KS patients (n = 366) to be diagnosed with alcohol problems (43% v 18%), noninjection drug use (45% v 18%), injection drug use (25% v 10%), psychosis (25% v 13%), and hypertension (13% v 2%). Although median CD4(+) count and HIV-1 viral load at the time of KS diagnosis were not significantly different between the two groups, significantly fewer (P < .01) HAART-era KS patients developed opportunistic illnesses (OIs) during their follow-up. The risk of dying among KS patients diagnosed in the HAART era is significantly lower (P < .01) than for KS patients diagnosed in the pre-HAART era (hazard ratio, 0.24). CONCLUSION: Although HAART-era KS patients in King County were as likely to have a depleted CD4(+) cell count and high HIV-1 viral loads at the time of KS diagnosis as pre-HAART KS patients, they survived longer and fewer of them were diagnosed with other OIs. They also had an increased prevalence of substance abuse and mental illness, contributing to a dynamic and changing KS clinical profile.     

AIDS-defining and non-AIDS-defining malignancies: cancer occurrence in the antiretroviral therapy era

PURPOSE OF REVIEW: Effective antiretroviral therapy use has resulted in a large number of older individuals living with HIV. Recent literature is reviewed with respect to the incidence and risk factors for cancer in HIV patients. RECENT FINDINGS: Previous studies have demonstrated substantial declines in AIDS-defining malignancies in the era of antiretroviral therapy, with clear links to better immune function. Increases in non-AIDS-defining malignancies such as Hodgkin's disease, skin, lung, anal, and kidney cancers have been noted by some but not all authors. Certain non-AIDS-defining malignancies may be related to immunodeficiency, although data are conflicting. Recent studies have indicated that confounding by traditional risk factors, including cigarette use, may account for some of the increased risk of lung and other cancers in HIV patients. SUMMARY: Non-AIDS-defining malignancies account for more morbidity and mortality than AIDS-defining malignancies in the antiretroviral therapy era. Traditional risk factors play a significant role in the increased risk of non-AIDS-defining malignancies for HIV-infected individuals, but do not entirely explain the excess cancer risk. Unanswered questions remain including the relationship of immunodeficiency and the risk of site-specific non-AIDS-defining malignancies, and the effect of antiretroviral therapy duration and drug class on cancer risk.     

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered.     

Human immunodeficiency virus-associated primary lung cancer in the era of highly active antiretroviral therapy: a multi-institutional collaboration

BackgroundHuman immunodeficiency virus (HIV)-infected individuals are at increased risk for primary lung cancer (LC). We wished to compare the clinicopathologic features and treatment outcome of HIV-LC patients with HIV-indeterminate LC patients. We also sought to compare behavioral characteristics and immunologic features of HIV-LC patients with HIV-positive patients without LC.Patients and MethodsA database of 75 HIV-positive patients with primary LC in the HAART era was established from an international collaboration. These cases were drawn from the archives of contributing physicians who subspecialize in HIV malignancies. Patient characteristics were compared with registry data from the Surveillance Epidemiology and End Results program (SEER; n = 169,091 participants) and with HIV-positive individuals without LC from the Adult and Adolescent Spectrum of HIV-related Diseases project (ASD; n = 36,569 participants).ResultsThe median age at HIV-related LC diagnosis was 50 years compared with 68 years for SEER participants (P < .001). HIV-LC patients, like their SEER counterparts, most frequently presented with stage IIIB/IV cancers (77% vs. 70%), usually with adenocarcinoma (46% vs. 47%) or squamous carcinoma (35% vs. 25%) histologies. HIV-LC patients and ASD participants had comparable median nadir CD4+ cell counts (138 cells/μL vs. 160 cells/μL). At LC diagnosis, their median CD4+ count was 340 cells/μL and 86% were receiving HAART. Sixty-three HIV-LC patients (84%) received cancer-specific treatments, but chemotherapy-associated toxicity was substantial. The median survival for both HIV-LC patients and SEER participants with stage IIIB/IV was 9 months.ConclusionMost HIV-positive patients were receiving HAART and had substantial improvement in CD4+ cell count at time of LC diagnosis. They were able to receive LC treatments; their tumor types and overall survival were similar to SEER LC participants. However, HIV-LC patients were diagnosed with LC at a younger age than their HIV-indeterminate counterparts. Future research should explore how screening, diagnostic and treatment strategies directed toward the general population may apply to HIV-positive patients at risk for LC.     

Cervical human papillomavirus infection and cervical intraepithelial neoplasia in women positive for human immunodeficiency virus in the era of highly active antiretroviral therapy

PURPOSE OF REVIEW: Human papillomavirus (HPV) has been strongly implicated in the pathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Women who are positive for the human immunodeficiency virus (HIV) have been shown to be at increased risk for cervicovaginal HPV infection and CIN, and cervical cancer is an acquired immunodeficiency syndrome-defining illness. The purpose of this review is to summarize recent studies of cervical HPV infection and CIN in HIV-positive women and to describe the effect of highly active antiretroviral therapy (HAART) on the course of CIN. RELEVANT FINDINGS: HIV-positive women have a higher prevalence of cervical HPV infection than HIV-negative women, and HPV infection is more persistent in the HIV-positive population. The incidence of high-grade CIN is increased in HIV-positive women. HAART has not been shown to affect HPV detection, and data on its effect on the natural history of CIN are mixed. Some studies show no effect of HAART on the natural history of CIN, and others show a statistically significant but modest beneficial effect. SUMMARY: Cervical HPV infection and CIN are clearly increased in HIV-positive women when compared with risk-matched HIV-negative women. HAART appears to have limited ability to clear HPV infection and induce regression of CIN in HIV-positive women. Combined with the high prevalence of cervical HPV infection and CIN, current data suggest that CIN should be aggressively sought and treated in HIV-positive women, including those who have responded well to HAART with good HIV viral load suppression and increasing CD4+ levels.     

Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.

PURPOSE: This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART. PATIENTS AND METHODS: Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir. RESULTS: The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL. CONCLUSION: Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.     

Systemic chemotherapy for HIV-associated lymphoma in the era of highly active antiretroviral therapy

Treatment of AIDS-associated non-Hodgkin lymphoma poses a complex and multifaceted challenge for the physician. Treatment responses to cytotoxic chemotherapy are relatively poor, relapse rates are high, and AIDS progression continues to be a major concern in patients receiving dose-intensive antilymphoma therapy. The recent advances in anti-HIV therapy have not seen a clear counterpart in improved antilymphoma therapy, but trials are underway that may help move this field forward. For patients who achieve a complete and durable response to antilymphoma therapy, potent antiretroviral therapy may help improve the prognosis from AIDS progression. Major questions persist, however, on the role of chemotherapy dose intensity, the best use of antiretroviral therapy during the administration of lymphoma therapy, and the optimal design of studies that can address these questions.     

AIDS-related malignancies: emerging challenges in the era of highly active antiretroviral therapy

Human immunodeficiency virus (HIV)-infected patients are at increased risk of developing cancer, particularly in the later stages of acquired immune deficiency syndrome (AIDS). Despite the advent of highly active anti-retroviral therapy (HAART), malignancy in this population is a leading cause of morbidity and mortality. Kaposi's sarcoma (KS) and AIDS-related non-Hodgkin's lymphoma (ARL) are the most common AIDS-defining malignancies. AIDS-related KS varies from minimal to fulminant disease. Treatment decisions for AIDS-related KS are guided largely by the presence and extent of symptomatic disease. In addition to HAART, excellent treatments exist for both localized disease (topical gel, radiotherapy, and intralesional therapy) and advanced disease (liposomal anthracyclines, paclitaxel). Novel therapies that have become available to treat AIDS-related KS include angiogenesis inhibitors and antiviral agents. ARL comprises a heterogeneous group of malignancies. With the immune restoration afforded by HAART, standard-dose chemotherapies now can be safely administered to treat ARL with curative intent. The role of analogous treatments used in HIV-negative patients, including monoclonal antibodies and autologous stem cell transplantation, requires further clarification in HIV-positive patients. HIV-infected patients also appear to be at increased risk for developing certain non-AIDS-defining cancers, such as Hodgkin's lymphoma and multiple myeloma. Although the optimal treatment of these neoplasms is at present uncertain, recent advances in chemotherapy, antiretroviral drugs, and supportive care protocols are allowing for more aggressive management of many of the AIDS-related cancers. This article provides an up-to-date review of the epidemiology, pathogenesis, clinical features, and treatment of various AIDS-related malignancies that are likely to be encountered by an oncologist practicing in the current HAART era.     

AIDS and cancer in the era of highly active antiretroviral therapy (HAART)

Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. Observational and time–trend data indicate that the incidence of Kaposi's sarcoma (KS) and primary brain lymphoma have decreased, but suggest that current therapies have not had a proportionate effect on systemic non-Hodgkin's lymphomas (NHL). As opportunistic infection and mortality are yielding to advances in antiretroviral therapy, lymphoma may increase in importance as a cause of AIDS-related morbidity and mortality. Further improvements in the long-term consequences of HIV infection will depend on better prevention and treatment of this serious malignant complication.