Metabolic Disturbances and Wasting in the Acquired Immunodeficiency Syndrome

Grünfeld, Carl; Feingold, Kenneth R.

doi:10.1056/nejm199207303270506

Cited by 352 publications

(12 citation statements)

References 78 publications

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“…Among untreated adults, there is an early decrease in HDL followed by decreases in LDL and increases in TG. 26 Chantry et al reported that, in a cohort of ART-naïve children, 30% had HDL abnormalities compared with 4% among a matched comparison group. 18 Among 103 ART-naïve children in London with mild/moderate HIV disease, median age 7.1 years, lipid levels were normal with the exception of below normal HDL.…”

Section: Discussionmentioning

confidence: 99%

Lipid Profiles in Young HIV-Infected Children Initiating and Changing Antiretroviral Therapy

Strehlau

Coovadia

Abrams

et al. 2012

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Both HIV infection and antiretroviral therapy are associated with dyslipidemias in adults but there are fewer data on outcomes in young children. Here we examined lipid profile changes in a cohort of young children before and after suppression on an initial ritonavir-boosted lopinavir (LPV/r)-based regimen and after switch to a nevirapine (NVP)-based regimen. Methods 195 HIV-infected children who initiated LPV/r-based therapy when <24 months of age at one site in Johannesburg, South Africa, and who achieved viral suppression (<400copies/ml sustained for ≥ 3 months) were randomised to either continue on the LPV/r-based regimen (n=99) or to switch to a NVP-based regimen (n=96). Non-fasting concentrations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) were measured pre-treatment, at randomization when suppressed, and at 9, 20 and 31 months post-randomization. Results Median age at treatment initiation was 9 months and the initial regimen was maintained for an average of 9 months before randomization. TC, LDL and HDL increased from pre-treatment to randomization (p<0.0001) and TC/HDL ratio and TG decreased (p<0.0001). After switching to NVP, HDL was significantly higher (p<0.02) and TC/HDL and TG significantly lower (p<0.0001) through 31 months post-switch relative to remaining on the LPV/r-based regimen. Conclusion Initiating antiretroviral therapy was associated with changes to a more favorable lipid profile in young children. Switching from a LPV/r-based regimen to a NVP-based regimen accentuated and continued these improvements. Investigation of safe and effective methods for managing dyslipidemias in children of different ages in resource-limited settings is warranted.

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Section: Discussionmentioning

confidence: 99%

Lipid Profiles in Young HIV-Infected Children Initiating and Changing Antiretroviral Therapy

Strehlau

Coovadia

Abrams

et al. 2012

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…About two-thirds were on a PI-based regimen, which in the majority of cases was boosted with ritonavir (RTV) (54% of SGA− and 59% of SGA+); EFV-based regimens were less common in SGA+ group compared to SGA− (see Supplemental Table). The two SGA groups did not differ in use of specific antiretrovirals known for causing more pronounced metabolic side effects (stavudine [D4T], ritonavir [RTV], zidovudine [ZDV], indinavir [IDV])(Grunfeld and Feingold, 1992). …”

Section: Resultsmentioning

confidence: 99%

“…Increased serum triglycerides in untreated HIV infection may represent a consequence of the systemic inflammatory response to persistent HIV infection (Grunfeld and Feingold, 1992). Thus, some of metabolic abnormalities may be attributable to neither ART nor SGAs.…”

Section: Discussionmentioning

confidence: 99%

The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk

Ferrara

Umlauf

Sanders

et al. 2014

Psychiatry Research

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To study the effect of concurrent use of second-generation antipsychotics (SGAs) on metabolic syndrome components conferring increased cardiovascular risk in a sample of HIV-infected adults taking ART. A retrospective study of participants consecutively recruited at the UCSD HIV Neurobehavioral Research Program examined effects of combined ART and SGAs on body mass index (BMI), nonfasting serum lipids, diabetes mellitus (DM) incidence, and mean arterial pressure (MAP). Metabolic outcome variables and covariates were compared using t-tests, Chi-squared or Fisher’s exact tests. Linear and logistic multivariable models explored metabolic outcomes for participants taking (SGA+) or not taking (SGA−) concomitant SGAs, after controlling for demographic and HIV disease- and ART-related covariates. Of 2229 HIV-infected participants, 12% (N=258) were treated with SGAs. In multivariable models adjusted for relevant covariates, the SGA+ group had significantly higher mean triglycerides, significantly higher odds of DM, significantly higher mean arterial pressures and marginally higher BMI. Use of SGAs in HIV-infected adults taking ART was independently associated with worse indicators of metabolic syndrome and cardiovascular risk. Aggressive monitoring for the metabolic complications from concurrent SGA and ART is indicated in all patients receiving these medication combinations.

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“…The impact of established chronic HIV infection in therapy-naive individuals is well documented by the incidence of gastrointestinal complications, including nutrient malabsorption, impaired immunity, and metabolic dysfunction. The role of infectious virus and viral antigens in the pathogenesis of immune dysfunction in HIV infection has been well investigated (4–7). However, our understanding of the early host-virus interactions at the mucosal sites is limited.…”

Section: Introductionmentioning

confidence: 99%

HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection

Jiang

Rocha

Hirao

et al. 2017

mBio

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Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4+ T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo. Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4+ T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4+ T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.

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Metabolic Disturbances and Wasting in the Acquired Immunodeficiency Syndrome

Cited by 352 publications

References 78 publications

Lipid Profiles in Young HIV-Infected Children Initiating and Changing Antiretroviral Therapy

Lipid Profiles in Young HIV-Infected Children Initiating and Changing Antiretroviral Therapy

The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk

HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection

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