Improved strategies for detecting HIV infection before AIDS-defining complications occur are needed in the era of HAART. The prevention of non-AIDS related cancers, especially lung cancer, the management of non-Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

BACKGROUNDBefore 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.METHODSAll 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.RESULTSOf 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 × 106 per liter; interquartile range [IQR], 35–231 × 106 per liter), and primary cerebral lymphoma (n = 27 [median CD4 count, 20 × 106 per liter; IQR, 4–109 × 106 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 × 106 per liter; IQR, 108–380 × 106 per liter) and 17 hemopathies (12 Hodgkin lymphomas, 4 myeloid leukemias, and 1 myeloma; median CD4 count, 113 × 106 per liter; IQR, 56–286 × 106 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.CONCLUSIONSMalignant 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. Cancer 2004. © 2004 American Cancer Society.

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The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

Highly active antiretroviral therapy (HAART) of human immunodeficiency virus-infected patients is associated with adverse effects, such as lipodystrophy and hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get insights into the physiopathological mechanisms underlying this syndrome, we treated mice with protease inhibitors (PIs) over a long period of time. Although atazanavir-treated mice presented the same circulating triglyceride concentration as control mice, lopinavir-ritonavir-treated mice rapidly became hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results obtained with mice reproduce the metabolic disorder observed in humans. White adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the control or atazanavir treatment, lopinavir-ritonavir treatment induced a significant 25% weight reduction in the peripheral inguinal WAT depot. By contrast, the profound epididymal WAT depot was not affected. This effect was associated with a 5.5-fold increase in SREBP-1c gene expression only in the inguinal depot. Our results demonstrate that the long-term treatment of mice with PIs constitutes an interesting experimental model with which some aspects of the lipoatrophy induced by HAART in humans may be studied.Highly active antiretroviral therapy (HAART) combines various protease inhibitors (PIs), nucleoside analogue reverse transcriptase inhibitors (NRTIs), and nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs). Whereas HAART efficiently suppresses human immunodeficiency virus (HIV) replication, long-term treatment of HIV-infected patients has been associated with a lipodystrophic syndrome and metabolic complications, with one of the most common complications being hypertriglyceridemia (6). The HAART-associated lipodystrophy is characterized by peripheral fat wasting in the face and limbs and the accumulation of visceral fat, breast hypertrophy, and cervical fat pads (buffalo hump) (7-9). Metabolic complications are preferentially associated with PI treatment and appear much more rapidly than lipodystrophy (20). It is not known whether the latter is a long-term consequence of the metabolic disorder or whether it corresponds to distinct molecular mechanisms. Because of the lack of a pertinent experimental model, the pathogenesis and physiopathological mechanisms by which PIs, NRTIs, and NNRTIs cause HAARTassociated lipodystrophy and metabolic disorders remain to be elucidated.PIs, NRTIs, and NNRTIs can interfere with adipocyte differentiation and adipocyte-specific gene expression (16,18,22,(26)(27)(28)(29). However, the reported effects are quite variable, positive or negative, depending on the molecule and on the experimental model studied. Furthermore, these cellular studies do not explain why HAART leads, in one case, to peripheral lipoatrophy and, in the other case, to abdominal...