scholarly journals Impact of HIV-1 Infection and Antiretroviral Therapy on Bone Homeostasis and Mineral Density in Vertically Infected Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
D. Donà ◽  
E. Mozzo ◽  
D. Luise ◽  
R. Lundin ◽  
A. Padoan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Hiv Infection ◽  
Antiretroviral Drugs ◽  
University Hospital ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Anthropometric Data ◽  
Hiv 1

Daily assumption of antiretroviral drugs and HIV-related immune activation lead to important side effects, which are particularly evident in vertically infected patients. Bone homeostasis impairment and reduction of bone mineral density (BMD) is one of the most important side effects. Primary aim of this study is to assess the prevalence of bone homeostasis alterations in a group of vertically infected patients; secondary aim is to analyze the relationship between bone homeostasis alterations and anthropometric data, severity of HIV infection, and antiretroviral therapy. We studied 67 patients with vertically transmitted HIV-1 (aged 6-31 years), followed by the Pediatric Infectious Disease Unit of the University Hospital of Padua, Italy. We analyzed bone turnover markers (P1NP and CTx) and we performed lumbar spine and femoral dual energy X-ray absorption densitometry (DXA). Personal and anthropometric data and information on HIV-infection severity and antiretroviral therapy were collected for all patients. We found that BMD values recorded by DXA showed a significant correlation with age, race, BMI, physical activity, and antiretroviral therapy duration. P1NP was increased in 43% of patients, while CTX in 61% of them. P1NP alteration was related to age, race, BMI, physical activity, therapy duration, and ever use of protease inhibitors and nucleotide reverse transcriptase inhibitors. CTX alteration was found to be correlated only with age. In conclusion, our study confirms that a wide percentage of HIV vertically infected patients show reduced BMD and impaired bone homeostasis. Strict monitoring is needed in order to early identify and treat these conditions.

scholarly journals HIV-1 CRF63_02A6 models as a tool for evaluating efficacy of developing antiretroviral drugs

2020 ◽  
Vol 10 (4) ◽  
pp. 769-774
Author(s):  
D. P. Zyryanova ◽  
N. V. Bogacheva ◽  
A. V. Totmenin ◽  
N. M. Gashnikova
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Federal District ◽  
Antiretroviral Drugs ◽  
Infection Process ◽  
Reverse Transcriptase Inhibitors ◽  
Infectious Molecular Clones ◽  
Hiv 1

Highly active antiretroviral therapy (HAART) allows not only to control the infection process in certain patient, but also to reduce a risk of HIV infection spreading in general, so that one of the goals for international community fighting against HIV-spread is to maximize coverage of infected subjects with HAART. Antiretroviral therapy in HIV infection is administered lifelong, so that therapeutic efficacy may be lowered due to emergence of resistant HIV-1 variants. Currently, development of new antiretroviral drugs is currently underway throughout the world, therefore standard HIV-1 models are demanded to evaluate antiviral efficacy of promising drugs. To reliably assess drug efficiency regarding Russiawide HIV-1 variants, HIV-1 genovariants widespread in Russia should be used as a virus model. A recently emerged recombinant form of CRF63_02A6 HIV-1 is spread in Russia being currently a dominant variant detected among HIV-infected individuals in an extended region of the Siberian Federal District: in the Novosibirsk, Tomsk, Omsk, Kemerovo Regions, Krasnoyarsk and Altai Krai. We have obtained CRF63_02A6 infectious isolates of HIV-1, one of which contains mutations, reducing the sensitivity to the applied inhibitors of the virus reverse transcriptase. In addition, we constructed infectious molecular clones based on HIV-1 CRF63_02A6 variants with an affinity for CCR5 coreceptors and CXCR4. Infectious isolates and molecular clones CRF63_02A6 tested as models for assessing efficacy of antiretroviral drugs using the example of the drug “Efavirenz”. The fifty percent inhibitory concentration determined on the models of HIV-1 infectious molecular clones and HIV-1 isolate 18RU7056 ranged from 0.00027 pg/ml to 0.00046 pg/ml being in agreement with data published elsewhere. Concentrations of “Efavirenz” used in the study did not suppress the replication of HIV-1 12RU6987, which is resistant to non-nucleoside reverse transcriptase inhibitors, which confirms the decrease in the sensitivity of HIV-1 12RU6987 to “Efavirenz” by no less than 10,000 times. Thus, our data demonstrate that CRF63_02A6 HIV-1 isolated strains and infectious molecular clones are relevant and complementary tools for assessing efficacy of developing drugs aimed at suppressing HIV-1, including non-nucleoside-resistant virus reverse transcriptase inhibitors.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk

2019 ◽  
Vol 17 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Barbara Altieri ◽  
Carolina Di Somma ◽  
Harjit pal Bhattoa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Physiological Role ◽  
Bone Diseases ◽  
Current Evidence ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Muscle Health

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.

scholarly journals Antiretroviral Drugs Impact Autophagy with Toxic Outcomes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman
Keyword(s):  
Quality Control ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Viral Suppression ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Foreign Material ◽  
Complete Understanding ◽  
Living With Hiv ◽  
Target Effects

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.

scholarly journals Detection of HIV-1 resistant to antiretroviral drugs among tomsk oblast population with newly diagnosed HIV-infection

2020 ◽  
Vol 12 (2) ◽  
pp. 88-96
Author(s):  
D. P. Zyryanova ◽  
E. M. Astakhova ◽  
M. P. Gashnikova ◽  
T. N. Ismailova ◽  
E. F. Bocharov ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Antiretroviral Drugs ◽  
Tomsk Oblast ◽  
Newly Diagnosed ◽  
Hiv 1

scholarly journals Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

2016 ◽  
Vol 90 (23) ◽  
pp. 10972-10980 ◽  
Author(s):  
Benoît Lacombe ◽  
Marina Morel ◽  
Florence Margottin-Goguet ◽  
Bertha Cecilia Ramirez
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Tat Protein ◽  
Aldosterone Antagonist ◽  
Hiv Transcription ◽  
Hiv Tat ◽  
Cellular Cofactor ◽  
Hiv 1

ABSTRACTTat protein, the HIV transactivator, regulates transcription of the HIV genome by the host transcription machinery. Efficient inhibitors of HIV transcription that target Tat or the cellular cofactor NF-κB are well known. However, inhibition of HIV Tat-dependent transcription by targeting the general transcription and DNA repair factor II human (TFIIH) has not been reported. Here, we show that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4+T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat-dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection. Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy.IMPORTANCETranscription from the HIV promoter is regulated by the combined activities of the host transcription machinery and the viral transactivator Tat protein. Here, we report that the drug spironolactone—an antagonist of aldosterone—blocks viral Tat-dependent transcription, thereby inhibiting both HIV-1 and HIV-2 infection of permissive T cells. This inhibition relies on the degradation of the cellular helicase XPB, a component of the TFIIH transcription factor complex. Consequently, XPB appears to be a novel HIV cofactor. Our discovery of the HIV-inhibitory activity of spironolactone opens the way for the development of novel anti-HIV strategies targeting a cellular cofactor without the limitations of antiretroviral therapy of drug resistance and high cost.

scholarly journals Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

2019 ◽  
Vol 57 (10) ◽  
Author(s):  
Mark M. Manak ◽  
Linda L. Jagodzinski ◽  
Ashley Shutt ◽  
Jennifer A. Malia ◽  
Mike Leos ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Western Blot ◽  
Research Collaboration ◽  
Virologic Suppression ◽  
Infection Status ◽  
Acute Hiv Infection ◽  
Western Blot Assay ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTAntiretroviral therapy (ART) during acute HIV infection (AHI) interrupts viral dynamics and may delay the emergence of serological markers targeted by current HIV screening and confirmatory assays, thus creating challenges for correctly classifying HIV infection status. The performance of three HIV antigen/antibody combination (HIV Ag/Ab Combo) assays (the Bio-Rad GS, Abbott Architect, and Bio-Rad BioPlex 2200 assays) was evaluated with samples collected from RV254/South East Asia Research Collaboration in HIV 010 (RV254/SEARCH010) study (Bangkok, Thailand) participants at weeks 12 and 24 following the initiation of ART at Fiebig stage I (FI) (n = 23), FII (n = 39), or FIII/IV (n = 22). Supplemental, confirmatory testing was performed by the Geenius HIV 1/2 and HIV-1 Western blot assays (Bio-Rad). Samples from 30 untreated, HIV-1-infected individuals demonstrated robust HIV Ag/Ab Combo assay reactivity with well-developed HIV-1 Western blotting profiles by 24 weeks after infection. In contrast, 52.2% of samples from individuals initiating ART at FI, 7.7% of samples from individuals initiating ART at FII, and 4.5% of samples from individuals initiating ART at FIII/IV were nonreactive by the HIV Ag/Ab Combo assays, with 36.4 to 39.1% of samples having low signal-to-cutoff (S/CO) results by the Architect and BioPlex assays (S/CO < 10). Seroreversion from a reactive to a nonreactive status was observed in 10 individuals initiating ART at FII and 3 individuals initiating ART at FIII/IV. The Geenius and HIV-1 Western blot assay results were negative or indeterminate for 73.9% and 69.6% of individuals, respectively, treated at FI; 50.0% and 26.3% of individuals, respectively, treated at FII; and 54.5% and 40.9% of individuals, respectively, treated at FIII/IV. Virologic suppression of HIV-1 by ART during AHI impedes seroconversion to biomarkers of infection, limiting the utility of HIV Ag/Ab Combo and supplemental, confirmatory assays for infection status determination.

scholarly journals Effect of antiretroviral therapy on bone turnover and bone mineral density in men with primary HIV-1 infection

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193679 ◽  
Author(s):  
Mariska C. Vlot ◽  
Marlous L. Grijsen ◽  
Jan M. Prins ◽  
Renate T. de Jongh ◽  
Robert de Jonge ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Antiretroviral Therapy ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Mineral Density ◽  
Hiv 1

Changes in bone mineral density over a 2-year period in HIV-1-infected men under combined antiretroviral therapy with osteopenia

AIDS ◽  
2013 ◽  
Vol 27 (15) ◽  
pp. 2425-2430 ◽  
Author(s):  
Lambert Assoumou ◽  
Christine Katlama ◽  
Jean-Paul Viard ◽  
Michelle Bentata ◽  
Anne Simon ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Antiretroviral Therapy ◽  
Bone Mineral ◽  
Mineral Density ◽  
Combined Antiretroviral Therapy ◽  
Hiv 1

scholarly journals Antiretroviral Therapy-Induced Functional Modification of IgG4 and IgM Responses in HIV-1–Infected Individuals Screened by an Allosteric Biosensor

2008 ◽  
Vol 13 (8) ◽  
pp. 817-821 ◽  
Author(s):  
Rosa María Ferraz ◽  
Miguel Angel Martínez ◽  
Rafael Cubarsi ◽  
Antonio Villaverde
Keyword(s):  
Antiretroviral Therapy ◽  
Structural Modification ◽  
Antiretroviral Treatment ◽  
Humoral Response ◽  
Antiretroviral Drugs ◽  
Functional Adaptation ◽  
Antiviral Immune Response ◽  
Immunodeficiency Virus ◽  
Target Epitope ◽  
Hiv 1

We have explored the effect of antiretroviral drugs on the antiviral immune response in human immunodeficiency virus-1 (HIV-1)—infected patients by using an enzymatic immunosensor that detects epitope-modifying anti-gp41 antibodies. By this molecular sensing approach, we have identified an irreversible impact of drug administration on the functionality of IgG4 and IgM specific antibodies regarding the structural modification promoted on their target epitope. During the antiretroviral therapy, the prevalent induced fit promoted by IgM on the epitope was lost at the expense of that promoted by IgG4, suggesting alternative-ness in the neutralization potency of these antibody subpopulations. Because the particular drug composition of the antiretroviral treatment did not affect such immune shift, the obtained data strongly suggest that the drop in the viral load and the consequent lost of antigenemia are responsible for the functional adaptation observed in the humoral response. ( Journal of Biomolecular Screening 2008:817-821)

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