6a5a76ecdc172a0c43a23b344c3e4c68 326785.pdf e24584ef95b01c6885f4662c47df9bf1f858a1cf 326785.pdf 4abf281441a2eaacdbae9db3481b25207c78219c8683b84c02b9406e61646aa1 326785.pdf Title: Lipodystrophy in HIV: Evolving Challenges and Unresolved Questions Subject: The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Keywords: lipodystrophy; HIV; antiretroviral treatment; lipoatrophy; obesity; lipomatosis Author: Marta Giralt, Pere Domingo, Tania Quesada-López, Rubén Cereijo and Francesc Villarroya Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jul 8 07:54:05 2025 CEST ModDate: Tue Jul 8 08:41:19 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 958075 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HSNNOI+URWPalladioL-Roma Type 1 Custom yes yes yes 10 0 VVMARY+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 ELJPLM+URWPalladioL-Ital Type 1 Custom yes yes yes 21 0 HLPNCF+PalatinoLinotype TrueType WinAnsi yes yes no 50 0 LDSSDS+EURM10 Type 1 Builtin yes yes yes 63 0 HLPNCF+PalatinoLinotype TrueType WinAnsi yes yes no 77 0 NTXOQV+VnURWPalladioL Type 1 Custom yes yes yes 99 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-03-18 04:14:53 CET RepresentationInformation: 326785.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-03-17 13:12:41 CET Size: 958075 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 386 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Causal Agents of Lipodystrophy in PLWH Destination: section.2 Children: Item: Title: Lipoatrophy Destination: subsection.2.1 Item: Title: Lipohypertrophy Destination: subsection.2.2 Item: Title: Lipomatosis Destination: subsection.2.3 Item: Title: Systemic Alterations in HIV-Associated Lipodystrophy Destination: subsection.2.4 Item: Title: Mechanisms Underlying HIV-Associated Lipodystrophy Destination: section.3 Children: Item: Title: Antiretroviral Treatment-Driven Effects Destination: subsection.3.1 Item: Title: HIV Infection-Related Effects Destination: subsection.3.2 Item: Title: Adipose Tissue Changes Under Modern Antiretroviral Regimens in PLWH Destination: section.4 Item: Title: Conclusions: Current Challenges for Management of Healthy Adipose Tissue in PLWH Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Lipodystrophy in HIV: Evolving Challenges and Unresolved Questions Author: Marta Giralt, Pere Domingo, Tania Quesada-López, Rubén Cereijo and Francesc Villarroya Subject: The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. 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