The document discusses various metabolic complications associated with HIV infection and antiretroviral therapy (HAART), including lactic acidemia, lipodystrophy, dyslipidemia, and insulin resistance. Lactic acidemia is proposed to result from mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) and can range from asymptomatic to potentially fatal lactic acidosis. Lipodystrophy involves abnormal fat redistribution including central lipohypertrophy and peripheral lipoatrophy, which are associated with prolonged HAART use and protease inhibitor therapy. Management of these conditions involves treatment interruption or switching antiretrovirals to limit toxicity.
This document summarizes advances in HIV treatment including HAART and its complications. It discusses how HAART effectively suppresses HIV but can have toxicities over the long term such as body changes, metabolic abnormalities, and liver or bone complications. Adherence is critical for treatment success. Resistance testing helps address treatment failure and resistance. New drugs and strategies continue to be developed and treatment interruption remains experimental. Management requires weighing risks and benefits of therapy changes and treatment goals.
D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 DuffusDSHS
The document discusses guidelines for initiating highly active antiretroviral treatment (HAART) based on CD4 count and viral load. Guidelines from 1998-2009 increasingly recommended treating HIV at higher CD4 counts and without a specific viral load threshold. Studies show the magnitude of CD4 increase is greatest when starting HAART at low counts, but normalization is more likely the earlier therapy begins. A CD4 count below 350 cells/mm3 increases the risk of cardiovascular and other non-AIDS complications.
Early initiation of haart why, when and how 21 juneanil kumar g
This document discusses guidelines for early initiation of HIV treatment. It recommends starting antiretroviral therapy (ART) for all people living with HIV, including pregnant and breastfeeding women, regardless of CD4 count or clinical stage. The benefits of early treatment include reduced progression to AIDS, lower rates of illness and death, and decreased HIV transmission. First-line ART regimens preferably include tenofovir, lamivudine and efavirenz. Viral load testing is the best way to monitor treatment response and detect treatment failure.
This is a presentation of Anti-Retroviral Therapy (ART) guidelines for HIV infection by the World Health Organization (WHO) updated as of December 2018.
This document discusses HAART (Highly Active Antiretroviral Therapy) for treating HIV. It describes the goals of ART in reducing morbidity and prolonging survival. It classifies antiretroviral drugs into five types that inhibit HIV enzymes or block viral entry. Common first line regimens are described along with guidelines for monitoring patients and changing therapy. It also outlines recommendations for preventing opportunistic infections in HIV-infected individuals.
C1_2 Michael Saag Chronic Disease in Longer-Term HIV PatientsDSHS
Strategies for Antiretroviral Therapy discusses when to start and how to finish HIV treatment. It notes that unchecked viral replication can lead to harm through inflammation, and that earlier treatment may be beneficial due to improved drug tolerability and reduced transmission risk. Studies show treating HIV can lower rates of illness and death, even at higher CD4 counts. Overall, current guidelines recommend considering treatment for asymptomatic patients with CD4 counts below 500, though some experts argue the benefits of starting at any CD4 count.
This document provides an introduction to HIV treatment, including guidelines on when to start treatment, current treatment options, and tips for getting the most out of treatment. The key points are:
- Current guidelines recommend antiretroviral therapy (ART) for all HIV-positive individuals, especially those with a CD4 count below 350 or those at risk of transmitting HIV.
- ART involves taking a combination of at least three antiretroviral drugs from two different classes to suppress the virus and prevent drug resistance. Common classes include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integra
This patient is a 40 year-old African American female who was diagnosed with asymptomatic HIV in 2003. She presents with well-controlled hypertension and a history of cocaine dependence. Her current CD4 count is 876 and viral load is undetectable. She has been coinfected with hepatitis B.
This document summarizes advances in HIV treatment including HAART and its complications. It discusses how HAART effectively suppresses HIV but can have toxicities over the long term such as body changes, metabolic abnormalities, and liver or bone complications. Adherence is critical for treatment success. Resistance testing helps address treatment failure and resistance. New drugs and strategies continue to be developed and treatment interruption remains experimental. Management requires weighing risks and benefits of therapy changes and treatment goals.
D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 DuffusDSHS
The document discusses guidelines for initiating highly active antiretroviral treatment (HAART) based on CD4 count and viral load. Guidelines from 1998-2009 increasingly recommended treating HIV at higher CD4 counts and without a specific viral load threshold. Studies show the magnitude of CD4 increase is greatest when starting HAART at low counts, but normalization is more likely the earlier therapy begins. A CD4 count below 350 cells/mm3 increases the risk of cardiovascular and other non-AIDS complications.
Early initiation of haart why, when and how 21 juneanil kumar g
This document discusses guidelines for early initiation of HIV treatment. It recommends starting antiretroviral therapy (ART) for all people living with HIV, including pregnant and breastfeeding women, regardless of CD4 count or clinical stage. The benefits of early treatment include reduced progression to AIDS, lower rates of illness and death, and decreased HIV transmission. First-line ART regimens preferably include tenofovir, lamivudine and efavirenz. Viral load testing is the best way to monitor treatment response and detect treatment failure.
This is a presentation of Anti-Retroviral Therapy (ART) guidelines for HIV infection by the World Health Organization (WHO) updated as of December 2018.
This document discusses HAART (Highly Active Antiretroviral Therapy) for treating HIV. It describes the goals of ART in reducing morbidity and prolonging survival. It classifies antiretroviral drugs into five types that inhibit HIV enzymes or block viral entry. Common first line regimens are described along with guidelines for monitoring patients and changing therapy. It also outlines recommendations for preventing opportunistic infections in HIV-infected individuals.
C1_2 Michael Saag Chronic Disease in Longer-Term HIV PatientsDSHS
Strategies for Antiretroviral Therapy discusses when to start and how to finish HIV treatment. It notes that unchecked viral replication can lead to harm through inflammation, and that earlier treatment may be beneficial due to improved drug tolerability and reduced transmission risk. Studies show treating HIV can lower rates of illness and death, even at higher CD4 counts. Overall, current guidelines recommend considering treatment for asymptomatic patients with CD4 counts below 500, though some experts argue the benefits of starting at any CD4 count.
This document provides an introduction to HIV treatment, including guidelines on when to start treatment, current treatment options, and tips for getting the most out of treatment. The key points are:
- Current guidelines recommend antiretroviral therapy (ART) for all HIV-positive individuals, especially those with a CD4 count below 350 or those at risk of transmitting HIV.
- ART involves taking a combination of at least three antiretroviral drugs from two different classes to suppress the virus and prevent drug resistance. Common classes include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integra
This patient is a 40 year-old African American female who was diagnosed with asymptomatic HIV in 2003. She presents with well-controlled hypertension and a history of cocaine dependence. Her current CD4 count is 876 and viral load is undetectable. She has been coinfected with hepatitis B.
The document discusses the goals of antiretroviral (ART) therapy in India, which include improving quality of life, reducing HIV-related illness and mortality, and maximally suppressing viral load. It outlines the classes of drugs used for ART, including reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and fusion inhibitors. The national program in India provides several first-line drug combinations. Principles for selecting first-line regimens include using lamivudine and choosing one NRTI and one NNRTI. Routine monitoring of ART patients and recommendations for treating HIV-infected pregnant women are also covered.
Discussion of the current medications of chronic hepatitis treatment in the Egyptian market as well as our protocol of management in the Viral Hepatitis Treatment Centers in Egypt. Discussion of the latest recommendations of AASLD/IDSA and EASL are presented
Arv active-toxcity-monitoring-gaberone-training-workshop-on-managmentprempanigrahi
This document outlines key aspects of monitoring and managing adverse drug reactions related to antiretroviral therapies. It discusses WHO recommendations for antiretroviral drugs, defines important terms like adverse drug reactions and treatment limiting toxicities, and describes the major toxicities associated with different antiretroviral regimens as well as approaches for clinical management. It also covers recommendations for routine and active toxicity monitoring.
Highly active antiretroviral therapy incidence of adverse drug reactionspharmaindexing
This document summarizes research on adverse drug reactions (ADRs) experienced by patients taking highly active antiretroviral therapy (HAART) to treat HIV/AIDS. Several studies cited found that the most common ADRs were anemia, hepatotoxicity, gastrointestinal issues, hematological issues, neurological issues, and skin problems. Risk factors for ADRs included CD4 count below 200 cells/μl, female gender, tuberculosis co-infection, and hepatitis C co-infection. While ADR rates were high, some studies found they did not often lead to HAART interruptions. Overall the document examines the incidence and types of ADRs experienced on HAART as well as risk factors. Close patient monitoring
An overview of the acquired immune deficiency syndrome (AIDS) caused by the human deficiency virus (HIV) and the drugs used for its treatment, including a classification of the established drugs, the HAART regimen, and investigational approaches
Highly Active Antiretroviral Therapy (HAART) involves using a combination of at least three antiretroviral drugs to suppress the HIV virus and stop the progression of HIV disease. HAART decreases the viral load, improves immune function, and prevents opportunistic infections. The goals of HAART are to prolong life, improve quality of life, achieve maximal viral suppression, restore immune function, reduce HIV transmission, and rationally sequence drugs to limit toxicity while maintaining treatment options. Current guidelines recommend starting ART for all individuals regardless of CD4 count. Second line regimens are recommended when clinical or immunological failure occurs on first line therapy. Managing adverse events and comorbidities like hepatitis co-infection is also
This document discusses HIV management and life expectancy after antiretroviral therapy (ART) initiation. A study of over 200,000 HIV patients in Thailand found that:
- Median life expectancy after starting ART at age 20 was 25.4 years, but was 51.9 years for those who started with CD4 counts over 350 cells/mm3.
- 83% of patients achieved undetectable viral loads. Starting ART earlier with higher baseline CD4 counts was associated with increased life expectancy.
- These results support guidelines recommending starting ART irrespective of CD4 count.
Key Facts over HIV by Dr. Milind KulkarniParvez Pathan
World AIDS Day 2014 focused on closing gaps in HIV prevention and treatment. The document discusses how HIV works by targeting the immune system, the stages of infection from acute to AIDS, transmission methods, risk factors, diagnosis, testing and counselling recommendations, prevention methods including condom use and medical male circumcision, antiretroviral treatment for prevention and care, harm reduction, and eliminating mother-to-child transmission. It notes that while access to antiretroviral treatment has increased in low and middle income countries, coverage must still be expanded to reach more children living with HIV.
The document discusses the viral genome, life cycle, and treatment of HIV. It notes that the viral genome contains three major open reading frames (gag, pol, env) that encode structural and enzyme proteins. It describes the life cycle steps of viral entry, replication, integration into the host genome, new virion assembly and budding. Regarding treatment, it explains that highly active antiretroviral therapy (HAART) involves combinations of antiviral drugs that target different stages of the viral life cycle. It provides details on various classes of antiretrovirals including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and integra
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
1) Hepatitis B vaccination faces several challenges, including ensuring safety, demonstrating efficacy of recombinant vaccines, determining duration of protection, addressing cost and non-responders.
2) Studies showed plasma-derived and recombinant vaccines provided protection for decades, though antibody levels declined over time. Cellular immune responses persisted despite low antibody levels.
3) Global elimination of Hepatitis B is possible by 2090 through high coverage birth dose vaccination, treatment of high-risk groups, and developing a cure for chronic infection. However, this will require significant ongoing financial investment.
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
Antiretroviral therapy what a general practitioner must knowParvez Pathan
This document summarizes current guidelines for antiretroviral therapy. It begins by stating that eradication of HIV is not currently possible due to reservoirs of latent infection. It then reviews recommendations for starting ART based on CD4 count from various organizations. A list of approved antiretrovirals is provided grouping them by class. The benefits of earlier treatment include reduced transmission risk, lower non-AIDS related mortality, and increased CD4 recovery. Studies supporting these benefits are summarized. Optimal first-line regimens now include tenofovir/emtricitabine due to lower toxicity compared to older drugs. Special considerations for ART in pregnancy and tuberculosis are discussed.
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document discusses guidelines for antiretroviral therapy in 2012. It outlines the different classes of antiretrovirals including NRTIs, NNRTIs, PIs, and newer drugs. It provides the NACO and API-ART guidelines for when to start ART based on WHO clinical staging and CD4 count. The preferred and alternative first-line ART regimens according to the NACO 2012 guidelines are described. Causes of first-line ART failure and the approach to second-line ART and resistance testing are summarized.
This document discusses guidelines for initiating Highly Active Anti-Retroviral Therapy (HAART) in adults and adolescents. It recommends starting ART when the CD4 count is below 350 cells/mm3 or the patient has an AIDS-defining illness, with the goal of maximal and durable viral suppression. Standard first-line ART regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Considerations before starting ART include assessing adherence, drug interactions, and patient factors like pregnancy.
1. The Diabetes Prevention Program (DPP) found that an intensive lifestyle intervention aimed at 7% weight loss was more effective than metformin or placebo at preventing diabetes in patients with prediabetes over 3 years, with a 58% reduction in relative risk.
2. For Mrs. K, an intensive lifestyle intervention targeting at least 7% weight loss would be the recommended first-line evidence-based approach based on the DPP findings.
3. After 1 year of lifestyle changes, Mrs. K had achieved 6% weight loss and normal fasting glucose and A1C levels, indicating response to treatment. However, 12 months later with 10 pounds regained, her glucose levels have
This document summarizes key elements of hepatitis C virus (HCV) treatment. The objectives of HCV treatment are to cure the virus and reduce health risks like liver disease. New direct-acting antiviral (DAA) drugs have improved cure rates above 95% by targeting the virus life cycle. DAA regimens are oral, short-course, and have minimal side effects. However, DAAs remain expensive in Vietnam and need price reductions through generics to increase treatment access and effectively reduce HCV prevalence when combined with harm reduction services.
The document discusses management of HIV in children in India. It describes three cases: 1) a 2.5 year old girl with failure to gain weight and recurrent infections who should start ART based on her clinical staging and CD4 count, 2) a 6 year old boy with pulmonary tuberculosis who should start anti-TB treatment first before ART to reduce the risk of immune reconstitution inflammatory syndrome (IRIS), and 3) a 6 year old boy who developed anemia likely due to zidovudine toxicity and requires substitution of his antiretroviral regimen. The document provides guidelines on when to start ART in children, appropriate first-line regimens, managing drug toxicities and co-infections like tuberculosis,
The document discusses non-alcoholic fatty liver disease (NAFLD), which includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is strongly associated with obesity and metabolic syndrome. The prevalence of NAFLD is increasing globally and varies from 5-30% in different regions. Diagnosis requires imaging and liver biopsy. Treatment focuses on lifestyle modifications and medications to improve insulin resistance.
The document discusses the proposal to change the name of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). It notes that NAFLD's name does not accurately capture the metabolic nature of the disease. The name change was proposed by an international panel of experts and aims to reduce stigmatization and increase consideration of the disease. If adopted, MAFLD would be used instead of NAFLD to describe fatty liver disease associated with metabolic dysfunction. The document supports the name change as a way to properly frame the growing epidemic of this liver disease.
The document discusses the goals of antiretroviral (ART) therapy in India, which include improving quality of life, reducing HIV-related illness and mortality, and maximally suppressing viral load. It outlines the classes of drugs used for ART, including reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and fusion inhibitors. The national program in India provides several first-line drug combinations. Principles for selecting first-line regimens include using lamivudine and choosing one NRTI and one NNRTI. Routine monitoring of ART patients and recommendations for treating HIV-infected pregnant women are also covered.
Discussion of the current medications of chronic hepatitis treatment in the Egyptian market as well as our protocol of management in the Viral Hepatitis Treatment Centers in Egypt. Discussion of the latest recommendations of AASLD/IDSA and EASL are presented
Arv active-toxcity-monitoring-gaberone-training-workshop-on-managmentprempanigrahi
This document outlines key aspects of monitoring and managing adverse drug reactions related to antiretroviral therapies. It discusses WHO recommendations for antiretroviral drugs, defines important terms like adverse drug reactions and treatment limiting toxicities, and describes the major toxicities associated with different antiretroviral regimens as well as approaches for clinical management. It also covers recommendations for routine and active toxicity monitoring.
Highly active antiretroviral therapy incidence of adverse drug reactionspharmaindexing
This document summarizes research on adverse drug reactions (ADRs) experienced by patients taking highly active antiretroviral therapy (HAART) to treat HIV/AIDS. Several studies cited found that the most common ADRs were anemia, hepatotoxicity, gastrointestinal issues, hematological issues, neurological issues, and skin problems. Risk factors for ADRs included CD4 count below 200 cells/μl, female gender, tuberculosis co-infection, and hepatitis C co-infection. While ADR rates were high, some studies found they did not often lead to HAART interruptions. Overall the document examines the incidence and types of ADRs experienced on HAART as well as risk factors. Close patient monitoring
An overview of the acquired immune deficiency syndrome (AIDS) caused by the human deficiency virus (HIV) and the drugs used for its treatment, including a classification of the established drugs, the HAART regimen, and investigational approaches
Highly Active Antiretroviral Therapy (HAART) involves using a combination of at least three antiretroviral drugs to suppress the HIV virus and stop the progression of HIV disease. HAART decreases the viral load, improves immune function, and prevents opportunistic infections. The goals of HAART are to prolong life, improve quality of life, achieve maximal viral suppression, restore immune function, reduce HIV transmission, and rationally sequence drugs to limit toxicity while maintaining treatment options. Current guidelines recommend starting ART for all individuals regardless of CD4 count. Second line regimens are recommended when clinical or immunological failure occurs on first line therapy. Managing adverse events and comorbidities like hepatitis co-infection is also
This document discusses HIV management and life expectancy after antiretroviral therapy (ART) initiation. A study of over 200,000 HIV patients in Thailand found that:
- Median life expectancy after starting ART at age 20 was 25.4 years, but was 51.9 years for those who started with CD4 counts over 350 cells/mm3.
- 83% of patients achieved undetectable viral loads. Starting ART earlier with higher baseline CD4 counts was associated with increased life expectancy.
- These results support guidelines recommending starting ART irrespective of CD4 count.
Key Facts over HIV by Dr. Milind KulkarniParvez Pathan
World AIDS Day 2014 focused on closing gaps in HIV prevention and treatment. The document discusses how HIV works by targeting the immune system, the stages of infection from acute to AIDS, transmission methods, risk factors, diagnosis, testing and counselling recommendations, prevention methods including condom use and medical male circumcision, antiretroviral treatment for prevention and care, harm reduction, and eliminating mother-to-child transmission. It notes that while access to antiretroviral treatment has increased in low and middle income countries, coverage must still be expanded to reach more children living with HIV.
The document discusses the viral genome, life cycle, and treatment of HIV. It notes that the viral genome contains three major open reading frames (gag, pol, env) that encode structural and enzyme proteins. It describes the life cycle steps of viral entry, replication, integration into the host genome, new virion assembly and budding. Regarding treatment, it explains that highly active antiretroviral therapy (HAART) involves combinations of antiviral drugs that target different stages of the viral life cycle. It provides details on various classes of antiretrovirals including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and integra
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
1) Hepatitis B vaccination faces several challenges, including ensuring safety, demonstrating efficacy of recombinant vaccines, determining duration of protection, addressing cost and non-responders.
2) Studies showed plasma-derived and recombinant vaccines provided protection for decades, though antibody levels declined over time. Cellular immune responses persisted despite low antibody levels.
3) Global elimination of Hepatitis B is possible by 2090 through high coverage birth dose vaccination, treatment of high-risk groups, and developing a cure for chronic infection. However, this will require significant ongoing financial investment.
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
Antiretroviral therapy what a general practitioner must knowParvez Pathan
This document summarizes current guidelines for antiretroviral therapy. It begins by stating that eradication of HIV is not currently possible due to reservoirs of latent infection. It then reviews recommendations for starting ART based on CD4 count from various organizations. A list of approved antiretrovirals is provided grouping them by class. The benefits of earlier treatment include reduced transmission risk, lower non-AIDS related mortality, and increased CD4 recovery. Studies supporting these benefits are summarized. Optimal first-line regimens now include tenofovir/emtricitabine due to lower toxicity compared to older drugs. Special considerations for ART in pregnancy and tuberculosis are discussed.
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document discusses guidelines for antiretroviral therapy in 2012. It outlines the different classes of antiretrovirals including NRTIs, NNRTIs, PIs, and newer drugs. It provides the NACO and API-ART guidelines for when to start ART based on WHO clinical staging and CD4 count. The preferred and alternative first-line ART regimens according to the NACO 2012 guidelines are described. Causes of first-line ART failure and the approach to second-line ART and resistance testing are summarized.
This document discusses guidelines for initiating Highly Active Anti-Retroviral Therapy (HAART) in adults and adolescents. It recommends starting ART when the CD4 count is below 350 cells/mm3 or the patient has an AIDS-defining illness, with the goal of maximal and durable viral suppression. Standard first-line ART regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Considerations before starting ART include assessing adherence, drug interactions, and patient factors like pregnancy.
1. The Diabetes Prevention Program (DPP) found that an intensive lifestyle intervention aimed at 7% weight loss was more effective than metformin or placebo at preventing diabetes in patients with prediabetes over 3 years, with a 58% reduction in relative risk.
2. For Mrs. K, an intensive lifestyle intervention targeting at least 7% weight loss would be the recommended first-line evidence-based approach based on the DPP findings.
3. After 1 year of lifestyle changes, Mrs. K had achieved 6% weight loss and normal fasting glucose and A1C levels, indicating response to treatment. However, 12 months later with 10 pounds regained, her glucose levels have
This document summarizes key elements of hepatitis C virus (HCV) treatment. The objectives of HCV treatment are to cure the virus and reduce health risks like liver disease. New direct-acting antiviral (DAA) drugs have improved cure rates above 95% by targeting the virus life cycle. DAA regimens are oral, short-course, and have minimal side effects. However, DAAs remain expensive in Vietnam and need price reductions through generics to increase treatment access and effectively reduce HCV prevalence when combined with harm reduction services.
The document discusses management of HIV in children in India. It describes three cases: 1) a 2.5 year old girl with failure to gain weight and recurrent infections who should start ART based on her clinical staging and CD4 count, 2) a 6 year old boy with pulmonary tuberculosis who should start anti-TB treatment first before ART to reduce the risk of immune reconstitution inflammatory syndrome (IRIS), and 3) a 6 year old boy who developed anemia likely due to zidovudine toxicity and requires substitution of his antiretroviral regimen. The document provides guidelines on when to start ART in children, appropriate first-line regimens, managing drug toxicities and co-infections like tuberculosis,
The document discusses non-alcoholic fatty liver disease (NAFLD), which includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is strongly associated with obesity and metabolic syndrome. The prevalence of NAFLD is increasing globally and varies from 5-30% in different regions. Diagnosis requires imaging and liver biopsy. Treatment focuses on lifestyle modifications and medications to improve insulin resistance.
The document discusses the proposal to change the name of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). It notes that NAFLD's name does not accurately capture the metabolic nature of the disease. The name change was proposed by an international panel of experts and aims to reduce stigmatization and increase consideration of the disease. If adopted, MAFLD would be used instead of NAFLD to describe fatty liver disease associated with metabolic dysfunction. The document supports the name change as a way to properly frame the growing epidemic of this liver disease.
The Indo-American Journal of Pharma and Bio Sciences and Journal publishes research articles, reviews and short communications. The scope of the journal is to publish manuscripts relating to Pharmaceutics, Pharmacology, Pharmacognosy & Phytochemistry,of the research journal.
The document discusses macrovascular complications in diabetes. It notes that atherosclerosis is an inflammatory disease and lists some theories of atherogenesis. It also discusses C-peptide and its potential role in atherosclerosis. Finally, it provides definitions of the metabolic syndrome from various organizations like WHO, ATP III, and IDF and notes unresolved questions regarding the metabolic syndrome.
Hígado graso no alcohólico en niños y adolescentes obesosCuerpomedicoinsn
The document discusses non-alcoholic fatty liver disease (NAFLD) and its relationship to obesity and insulin resistance. It notes that NAFLD affects around 20% of adults and 5% of children, and is strongly associated with obesity. A small portion of NAFLD cases progress to non-alcoholic steatohepatitis (NASH), which can potentially lead to scarring, cirrhosis, and liver failure over many years if not treated or reversed. Lifestyle changes such as weight loss and increased physical activity are recommended for treatment.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide, affecting up to 25% of the general population. It is strongly associated with obesity, type 2 diabetes, and metabolic syndrome. The pathogenesis involves insulin resistance leading to fatty infiltration of the liver followed by oxidative stress causing inflammation and fibrosis. Clinical features are often asymptomatic, though elevated liver enzymes and hepatomegaly may be seen. Diagnosis relies on excluding other causes of liver disease and imaging or biopsy. Potential therapies focus on lifestyle changes like diet, exercise and weight loss as well as treatments targeting underlying conditions and antioxidants.
Non-Alcoholic Fatty Liver Disease (NAFLD)Sariu Ali
Nonalcoholic fatty liver disease (NAFLD) is defined as hepatic steatosis without significant alcohol consumption or other known liver diseases. It includes nonalcoholic fatty liver (NAFL) characterized by hepatic fat accumulation without inflammation or fibrosis, and nonalcoholic steatohepatitis (NASH) characterized by fat accumulation with inflammation and hepatocyte injury. NAFLD is strongly associated with obesity and metabolic syndrome. Lifestyle interventions including weight loss and exercise are recommended first-line treatment, while pioglitazone and vitamin E may improve liver histology in non-diabetic adults with NASH. Liver biopsy is needed to distinguish NASH from NAFL and assess fibrosis to guide management.
Treating Cholesterol in Asian Patients: Balancing the Risk and Benefitsahvc0858
This document summarizes a presentation on treating cholesterol in Asians given by Dr. Jeremy Chow. It discusses the prevalence of hyperlipidemia in Singapore, challenges with statin usage in Asians including common myths, and new cholesterol targets for high-risk patients. It provides examples of managing different patient cases, including lifestyle modifications, medications such as statins and PCSK9 inhibitors, and balancing risks and benefits of treatment.
This document provides an overview of nonalcoholic fatty liver disease (NAFLD). It defines NAFLD and discusses its prevalence, risk factors, pathogenesis involving insulin resistance and lipid peroxidation, natural history including progression to nonalcoholic steatohepatitis (NASH) and fibrosis, clinical features such as elevated liver enzymes and asymptomatic presentation, diagnosis using imaging and biopsy, and treatment options focusing on weight loss through diet and exercise. The pathogenesis involves fat accumulation due to insulin resistance followed by lipid peroxidation and inflammation. Sustained weight loss through lifestyle changes is the primary treatment recommendation.
This document provides an overview of autoimmune hepatitis (AIH) including epidemiology, clinical presentation, diagnosis, treatment, and management. Some key points:
- The prevalence of AIH is highest in Alaska Natives at around 117 per 100,000 people.
- AIH most often presents as either acute hepatitis with jaundice or chronic hepatitis with elevated liver enzymes. Liver biopsy is necessary to confirm diagnosis.
- Diagnosis is based on elevated autoantibodies and elevated IgG along with supportive biopsy findings. The most common types are type 1 and type 2 defined by specific autoantibodies.
- Treatment involves immunosuppression with corticosteroids and azathioprine to induce
This document contains the results of laboratory tests performed on a 62-year-old female. The tests measured levels of components in the blood including hemoglobin, white blood cells, platelets, proteins, liver enzymes, glucose, lipids, electrolytes, kidney and liver function. Most results were within normal ranges, though the patient had elevated erythrocyte sedimentation rate and low levels of vitamin D and B12.
This document summarizes a teleconference on diabetes and metabolic syndrome in patients hospitalized with cardiovascular disease. It discusses screening for diabetes and metabolic syndrome in hospitalized CVD patients, defines metabolic syndrome, reviews the prevalence and risk factors associated with it, and how metabolic syndrome predicts diabetes and increased cardiovascular risk. It also reviews inpatient management of hyperglycemia and metabolic syndrome.
Acute Fatty Liver of Pregnancy (AFLP) is a rare but serious condition that affects 1 in 7,000-11,000 pregnancies. It is characterized by fatty infiltration and cellular dysfunction in the liver during late pregnancy or early postpartum. Prompt delivery is the recommended treatment as the condition does not typically improve until after delivery, and maternal and fetal mortality rates are high if not treated properly. Diagnosis is based on clinical presentation and lab tests in the absence of a definitive causative agent or diagnostic test. Close monitoring of future pregnancies is advised for women previously affected by AFLP.
Core Components of the Metabolic Syndrome in Nonalcohlic Fatty Liver DiseaseIOSR Journals
This study examined the association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in Bangladeshi patients. The study included 67 patients diagnosed with NAFLD and 50 healthy controls matched for age and BMI. Results found that NAFLD patients had higher levels of insulin resistance, triglycerides, and central obesity compared to controls. However, no significant association was found between MetS and NAFLD when defined by common diagnostic criteria. Individual components of MetS like dyslipidemia, central obesity, and high postprandial glucose were significantly associated with NAFLD on logistic regression analysis. The study concludes that while various MetS components are linked to NAFLD in
This document discusses cirrhosis of the liver and its dietary management. It begins with defining cirrhosis as a diffuse process characterized by liver necrosis, fibrosis and conversion of normal liver architecture into abnormal nodules. It then outlines the common causes of cirrhosis including chronic alcoholism, hepatitis B/C, autoimmune diseases and others. The document discusses the pathophysiology of cirrhosis and its clinical manifestations. It also covers nutritional assessment of patients with cirrhosis and recommendations for their dietary management including adequate caloric, protein and fiber intake as well as supplementation of vitamins, minerals and branched-chain amino acids.
Hepatotoxicity, or liver toxicity, can result from anti-tuberculosis (TB) drugs and is known as drug-induced hepatitis (DIH). Patients at high risk include those with pre-existing liver conditions, alcohol use, and advanced TB. Monitoring of liver enzymes is important for high risk patients during TB treatment. Symptoms of DIH include fatigue, nausea, and jaundice. Diagnosis involves abnormal liver enzymes and symptom resolution after stopping anti-TB drugs. Management consists of gradual dose escalation while monitoring for toxicity.
Lactic acidosis (LA) is a type of metabolic acidosis caused by lactic acid buildup in the body. There are two main types - type A due to tissue hypoxia, and type B which is not caused by hypoxia. Type B includes subtypes B1 associated with underlying diseases, B2 caused by certain drugs and toxins, and B3 involving inborn errors of metabolism. LA can be diagnosed through patient history, symptoms, and laboratory tests showing acidosis and elevated lactate levels. Treatment focuses on addressing the underlying cause, improving oxygen delivery for type A, and correcting metabolic or drug issues for type B. Prognosis depends on the severity and underlying condition, with mortality rates over 60
This document discusses the classification and cellular mechanisms of opioid receptors. There are four main types of opioid receptors: mu, delta, kappa, and ORL-1. Each receptor type is activated by different endogenous peptides and exogenous drugs. When activated, the receptors modulate various central and physiological processes like pain, locomotion, stress, and reward/addiction pathways. The document provides an overview of the endogenous and exogenous agonists and antagonists that act on each receptor subtype.
This document discusses clinical pharmacokinetics and pharmacodynamics. It defines pharmacokinetics as how the body affects a drug through absorption, distribution, metabolism and elimination. Factors like age can impact these processes in pediatric patients. It also discusses pharmacodynamics, how drugs act on the body, and how pharmacokinetics and pharmacodynamics together can help individualize drug therapy and decrease adverse effects.
- Pharmacokinetics is the study of the absorption, distribution, metabolism, and excretion of drugs in the body over time. It aims to quantitatively account for the amount of drug in the body and the rate it is cleared.
- Distribution of drugs throughout tissues is affected by factors like membrane permeability, blood flow, lipid solubility, pH, and plasma protein binding. The apparent volume of distribution indicates how much volume a drug appears to distribute into based on its concentration in plasma.
- Clearance is the rate of drug elimination from plasma relative to its concentration and depends on hepatic and renal elimination. It is used to calculate maintenance dosing to achieve a target concentration.
This document provides an overview of pharmacokinetic concepts including the four main processes of absorption, distribution, metabolism, excretion, and various pharmacokinetic models. It discusses how drugs move through the body, factors that affect drug concentrations over time, and complexity of drug interactions within the body. Examples are provided to illustrate key pharmacokinetic principles such as the effect of dosage form on absorption rate and how organ function influences drug elimination rates.
Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion in the body. The key pharmacokinetic parameters include volume of distribution (Vd), clearance (CL), and elimination half-life (t1/2). Vd represents the apparent volume needed to contain the total amount of drug at the observed plasma concentration. CL is the volume of plasma cleared of drug per unit time, determined by metabolism and excretion. t1/2 is the time for drug concentration to reduce by half, dependent on Vd and CL. These parameters allow quantification of drug behavior in the body over time.
Cephalosporins are a class of beta-lactam antibiotics that share a beta-lactam ring structure with penicillins and other beta-lactams. They work by binding to penicillin-binding proteins in bacterial cell walls to inhibit cell wall synthesis. First generation cephalosporins are mainly active against gram-positive cocci, while later generations have increased gram-negative coverage. Each generation also has distinct and expanded clinical uses depending on their antimicrobial spectrum.
This document discusses various antibiotics, their uses, and emerging issues with antibiotic resistance. It provides guidance on empiric treatment for common infections like community-acquired pneumonia and skin/soft tissue infections.
For a case of community-acquired pneumonia, the patient was initially treated empirically with Augmentin and clarithromycin per guidelines. Testing later found penicillin-resistant Streptococcus pneumoniae, requiring a change to higher dose beta-lactams, vancomycin, or fluoroquinolones.
A case of cellulitis grew methicillin-resistant Staphylococcus aureus despite initial Augmentin treatment. The drug of choice for MRSA is vancomycin,
The document discusses ovarian cancer treatment and management. It covers symptoms, risk factors, diagnosis methods, surgical staging and debulking, chemotherapy options including the gold standard of intravenous carboplatin and paclitaxel as well as emerging intraperitoneal chemotherapy showing increased survival. It emphasizes the importance of complete surgical staging and aggressive cytoreductive surgery for optimal outcomes and challenges of ensuring all patients receive standard of care treatment by gynecologic oncologists.
- Ovarian cancer is the 4th leading cause of cancer death in women in the US, with a 5-year survival rate of only 35% for advanced cases. Most cases are diagnosed at an advanced stage due to non-specific early symptoms.
- There is no consensus on screening guidelines due to a lack of evidence that screening reduces mortality. Current screening methods like ultrasound and CA-125 lack sensitivity and specificity.
- Several large trials are underway to evaluate new screening strategies using ultrasound, tumor markers, and genetic testing to enable earlier detection when treatment is most effective. Improved screening methods are needed to reduce ovarian cancer mortality rates.
This document discusses hereditary breast and ovarian cancer and the role of genetics in cancer risk. It provides an overview of BRCA1 and BRCA2 genes which are known to increase the risk of breast and ovarian cancers when mutated. Individuals with mutations in these genes have a high lifetime risk, up to 85%, of developing breast cancer and 16-44% risk for ovarian cancer. Referral to a cancer genetics clinic is recommended for those with a strong family history or personal history of related cancers to determine risk and recommend screening and management options.
1. Ovarian cancer is the most common type of ovarian tumor and the 7th most common cancer in women.
2. Early stages of ovarian cancer are often asymptomatic but later stages can cause pressure symptoms like abdominal pain or bloating.
3. Ovarian cancer commonly spreads directly to nearby structures in the abdomen or through the lymphatic system to distant lymph nodes.
Ovarian cancer is the 8th most common cancer in women and the 5th leading cause of cancer death. It has a median age of diagnosis of 60 years old and 68% of cases are metastatic at diagnosis. Risk factors include family history, personal history of breast cancer, infertility, and lack of pregnancy. Genetic mutations like BRCA1/2 account for 10-15% of cases. Symptoms are often vague. Treatment involves surgical staging and debulking followed by platinum-based chemotherapy, with the goal of optimal cytoreduction to ≤1cm residual disease.
The document discusses the evaluation and management of incidental adrenal lesions, or "incidentalomas", discovered on imaging. It outlines criteria for categorizing incidentalomas as benign, indeterminate low/intermediate/high risk, or malignant based on imaging features and patient history. Benign lesions may require no follow up, while potentially malignant lesions are further evaluated using imaging algorithms, biopsy, or functional testing to establish a diagnosis and guide management.
This document summarizes genetic alterations involved in the progression of well-differentiated thyroid carcinomas to poorly differentiated and anaplastic carcinomas. It discusses mutations in genes such as BRAF, RAS, RET/PTC, and PAX8-PPARγ that are involved in early-stage well-differentiated and follicular carcinomas. Additional mutations in p53 and β-catenin are thought to direct dedifferentiation and progression to later stages. Studies of mutations and loss of heterozygosity support a model where well-differentiated tumors progress through poorly differentiated to anaplastic carcinomas through the accumulation of these genetic alterations.
1. The patient has a history of thyroid cancer with metastases to the lungs and skull, and underwent total thyroidectomy and parathyroidectomy.
2. Treatment options for recurrent or metastatic thyroid cancer include radioactive iodine treatment, surgery, external beam radiation, and molecularly targeted therapies.
3. Molecular targeted therapies that show promise for thyroid cancer work by inhibiting pathways involved in cell signaling and angiogenesis, such as the MAPK and PI3K pathways, or by restoring radioiodine uptake.
- Thyroid cancer accounts for 1.5% of cancers in the US, with papillary carcinoma being the most common at 80% of cases.
- A 45-year-old female presented with a thyroid nodule that was found to be papillary carcinoma on biopsy. Near-total or total thyroidectomy is the recommended treatment.
- Her prognosis is favorable at ~90% 10-year survival given her diagnosis of papillary carcinoma and surgery. Ongoing monitoring is still recommended.
1. Thyroid cancer is the most common endocrine malignancy, with papillary thyroid cancer being the most common type.
2. Treatment involves surgical removal of part or all of the thyroid gland followed by radioactive iodine ablation and thyroid hormone suppression.
3. Follow up care involves monitoring of thyroid levels and imaging tests to check for recurrence or spread of cancer. Outcomes depend on cancer type, stage, and individual risk factors.
1. New diagnostic criteria have been developed to clarify the diagnosis of Sjogren's syndrome and diminish confusion in clinical practice and research.
2. The diagnosis of Sjogren's syndrome can be challenging as minor salivary gland biopsies and ANA blood tests sometimes have variable or non-specific results.
3. While Sjogren's syndrome and SLE share some similarities, Sjogren's syndrome has distinct clinical manifestations and treatment considerations compared to SLE.
1) The document discusses Sjogren's Syndrome, an autoimmune disease characterized by dry eyes and mouth, and evolving concepts for treating it based on pathogenesis involving lymphocytic infiltrates impairing salivary and lacrimal gland function rather than full destruction.
2) It explores using the muscarinic receptor agonist cevimeline to stimulate residual gland function by activating M1/M3 receptors, and insights from Sjogren's into related conditions involving dryness from cholinergic imbalances like multiple sclerosis, Alzheimer's, and fibromyalgia.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
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8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
5. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids 0
6. CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs NRTI-induced mitochondrial toxicity Proposed Pathogenesis 0
7. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs 0
8. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs 0
9. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs 0
10. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs 0
11. NRTI-induced mitochondrial toxicity Proposed Pathogenesis CELL glucose pyruvate lactate Acetyl CoA Krebs cycle NADH FADH 2 Oxidative phosphorylation ATP MITOCHONDRION mtDNA DNA pol γ Fatty Acids NRTIs 0
12. Classification of Lactic Acidemia *Symptoms and signs that suggest lactic acidemia consist of nausea, vomiting, abdominal pain, weight loss, fatigue, myalgias, abdominal distention, abdominal pain, dyspnea, and cardiac dysrhythmias. Source: HIV Web Study (www.hivwebstudy.org); Schambelan M et al. JAIDS 2002;31:257-75 0
13.
14. Risk Factors for the Development of Lactic Acidemia in Persons Taking NRTIs *Most cases have involved stavudine **Especially with the use of stavudine plus didanosine Source: HIV Web Study (www.hivwebstudy.org) 0
15.
16. Recommendations for the Management of Lactic Acidemia Source: HIV Web Study (www.hivwebstudy.org); Carr A. Clin Infect Dis 2003;36 (Suppl 2):S96-100. 0
31. Risk Factors for Lipoatrophy and Lipohypertrophy Lichtenstein KA. JAIDS 2005;39:395-400. Percentage of studies showing statistically significant associations between risk factors and either lipoatrophy (LA) (9 studies) or lipohypertrophy (LH) (8 studies) using multivariate analysis.
48. J Acquir Immune Defic Syndr 2002 February 1;29(2):117-121 ? Etiology of Lipoatrophy: Evidence of Mitochondrial Toxicity in Adipocytes
49. HIV infection may independently contribute to mitochondrial toxicity Non-HIV Infected (n = 24) HIV Infected, naïve to antiretrovirals (n = 47) HIV Infected, with mitochondrial toxicity, before stopping ARVs (n = 8) HIV Infected, with mitochondrial toxicity, after stopping ARVs (n = 7) N Engl J Med 2002; 346:811-820, Mar 14, 2002. mtDNA:nDNA ratio
63. The DAD Study Group, N Engl J Med 2003;349:1993-2003 Incidence of Myocardial Infarction According to the Duration of Exposure to Combination Antiretroviral Therapy
64. The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group, N Engl J Med 2003;349:1993-2003 0
65.
66. Switch HAART regimen or initiate lipid-lowering pharmacotherapy? Trend of mean plasma triglyceride levels of 130 evaluable patients switched from protease inhibitor to nevirapine (arm A) or efavirenz (B), or treated with pravastatin (C) or bezafibrate (D), at baseline and after 3, 6, 9 and 12 months of follow-up. Calza L et al. AIDS 2005: 19(10), 1051-8.
67. Switch HAART regimen or initiate lipid-lowering pharmacotherapy? Trend of mean plasma total cholesterol levels of 130 evaluable patients switched from protease inhibitor to nevirapine (arm A) or efavirenz (B), or treated with pravastatin (C) or bezafibrate (D), at baseline and after 3, 6, 9, and 12 months of follow-up. Calza L et al. AIDS 2005: 19(10), 1051-8.
75. Studies on Osteopenia in HIV Adapted from Arnsten JH et al, 10 th CROI, Boston 2003, Abstract 103 * combined prevalence of osteopenia and osteoporosis Study Sample Prevalence* Risk Factors Carr, 2001 Australia 221 HIV+ men, Wt. 70-75 kg 25% Lactate level low weight Huang, 2001 Boston, MA 41 HIV+ men, BMI 25 18 HIV- men, BMI 25 BMD reduced in HIV+ men w/ high visceral fat Historical low weight; high visceral fat McDermott, 2001 New England 203 HIV+ men, BMI 24 62 HIV+ women, BMI 25 BMC reduced in men on HAART HAART use and duration Knobel 2001 Spain 58 HIV+ men, 22 HIV+ women, BMI 23 overall 100 HIV- controls, BMI 23 89% in HIV+ 30% in HIV- Weight, BMI Nolan, 2001 Australia 183 HIV+ men BMI 23-24 56% in PI-treated; 49% in PI-naïve Low pre-HAART BMI; Indinavir protective Gold, 2002 Australia 110 HIV+ men lean mass 57 kg 55% Age, lean body mass, duration of NRTI use Mondy, 2003 St. Louis, MO 108 HIV+ men, 17 HIV+ women; BMI 25 46% BMI, smoking, wt loss, steroids Arnsten, 2003 New York, NY 200 HIV+ women: BMI 28 205 HIV- women: BMI 32 30% in HIV+ 24% in HIV- Age, race, BMI; PI use > 1 year protective
Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000;14:F25-32. Boubaker K, Flepp M, Sudre P, et al A. Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study. Clin Infect Dis. 2001;33:1931-7. Moyle GJ, Datta D, Mandalia S, Morlese J, Asboe D, Gazzard BG. Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors. AIDS. 2002;16:1341-9. Lafeuillade A, Hittinger G, Chadapaud S. Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet. 2001;357:280-1. Bonnet F, Bonarek M, Morlat P, et al. Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study. Clin Infect Dis. 2003;36:1324-8. Arenas-Pinto A, Grant AD, Edwards S, Weller IV. Lactic acidosis in HIV infected patients: a systematic review of published cases. Sex Transm Infect. 2003;79:340-4.
1
The HOPS is a well-established cohort of patients from a number of US treatment centers, and is coordinated by the Centers for Disease Control and Prevention. A prospective analysis was presented on 337 patients who had no sign of lipoatrophy in an initial assessment, and who were evaluated again 21 months later to identify factors associated with the development of lipoatrophy. [5] Standardized interviews and physician assessments of clinical signs were performed on each occasion. The incidence of moderate or severe fat loss of the extremities, hips, or buttocks and sunken cheeks (without total body weight loss, to differentiate such cases from HIV wasting) was analyzed, and multivariate analyses were performed to assess their relationship to immunologic, virologic, clinical, and drug treatment variables. The proportion of patients who developed moderate or severe lipoatrophy between the 2 surveys was 13.1% (44 of 337 patients). This is broadly in accordance with the 2-year rates of new onset reported in other studies. [6] Multivariate analyses indicated that disease and host factors were more critical to the development of new lipodystrophy than were drug factors. Specifically, white race was associated with a 5-fold increase in the relative odds of developing lipodystrophy. This racial association has been reported previously and may be linked to the relative prevalence of specific TNF-a promoter genes in the white population. The CD4+ cell count nadir and the magnitude of change in the CD4+ cell count were also associated with increased risk: Individuals with a history of a CD4+ cell count < 100 cells/mm 3 and those whose CD4+ cell count had risen by < 100 cells/mm 3 were more likely to develop lipodystrophy. Individuals with body mass index < 24 had a 2.4-fold greater odds of developing lipodystrophy. There was no association between the onset of lipoatrophy and duration, initiation, continuation, or discontinuation of any antiretroviral medication. Where does this study point us in the investigation and management of lipoatrophy? Certainly away from drugs and more towards the way in which the immune system recovers in an individual. Avoidance of a low CD4+ cell count may be a critical issue in reducing the risk of lipoatrophy, which may have implications for the debate regarding when to start antiretroviral therapy. Equally important may be dietary interventions to aggressively manage weight loss before it becomes substantial. The use of immune modulators may also have a role, because achieving a rapid increase in CD4+ cell count may reduce the risk of lipoatrophy. This question is being examined in substudies of the SILCAAT and ESPRIT studies of interleukin-2. Finally, if white race is a specific risk factor for lipoatrophy, we need to identify the genetic differences between whites and other ethnicities that might reveal potentially modifiable genetic markers of risk of lipodystrophy; eventually, treatment guidelines may need to consider different approaches for patients of different ethnic backgrounds. Lichtenstein K, Delaney K, Ward D, Moorman A, Wood K, Holmberg S. Incidence and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients. Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 684a.
So the initial perception that lipoatrophy and lipohypertrophy stem from a single central mechanism is probably not true, but the two disorders do share a number of risk factors.
A further study in 2258 HIV-positive patients assessed adipose tissue alterations by gender.16 Logistic regression analysis demonstrated that men had a significantly lower adjusted risk of presenting with any alteration than women (OR: 0.47; 95% CI: 0.38–0.58; P , 0.0001) and a significantly lower risk of lipohypertrophy (P = 0.0022) and mixed fat redistribution (P , 0.0001), whereas risk of lipoatrophy was similar between genders.
The enzyme 11-b-HSD1 has also been implicated as potentially playing a role in fat redistribution syndromes. This enzyme helps catalyze the conversion of the hormonally inactive cortisone to cortisol, which is required for adipocyte differentiation. It is expressed to a higher degree in visceral fat than in subcutaneous fat and is elevated in the presence of cortisol. The differential expression of 11-b-HSD1 in visceral fat, its association with cortisol, and the well-established prevalence of elevated cortisol levels in HIV suggest that this enzyme may play a role in the pathogenesis of central fat accumulation in HIV.26
Rosiglitazone increases subcutaneous fat in type 2 diabetic patients and reverses the block of adipocyte differentiation induced by HAART in vitro
Rosiglitazone increases subcutaneous fat in type 2 diabetic patients and reverses the block of adipocyte differentiation induced by HAART in vitro
Rosiglitazone increases subcutaneous fat in type 2 diabetic patients and reverses the block of adipocyte differentiation induced by HAART in vitro
To investigate if possible mitochondrial injury can be found in adipose tissue of nucleoside analogue reverse transcriptase inhibitor (NRTI)–treated patients, subcutaneous fat was taken from the buttocks of 24 HIV-positive patients and 8 HIV-negative controls. The content of mitochondrial DNA (mtDNA) was quantified using a Southern blot technique. Fat biopsies were examined by electron microscopy and screened by restriction fragment length polymorphism analysis for the presence of the nt 8344 and 3243 mtDNA point mutations. Age, sex, and body mass index did not differ between the HIV-negative controls, the HIV-positive patients currently treated with NRTIs (NRTI group, n = 19), and the HIV-positive patients without NRTIs (no-NRTI group, n = 5). The mean mtDNA content was 44% lower in the NRTI group compared with the no-NRTI group ( p = .01) but did not differ between the control group and the no-NRTI group. When the HIV-infected patients were stratified to a group with clinical signs of lipoatrophy at the biopsy site (LA group, n = 11) and a group without lipoatrophy (no-LA group, n = 13), the mean mtDNA content in the LA group was 39% lower than that in the no-LA group ( p = .02). No point mutations or deletions were observed. The adipocytes of patients with lipoatrophy contained multiple small lipid vacuoles, and the mitochondria harbored inclusions reminiscent of mtDNA cytopathies. mtDNA depletion and ultrastructural abnormalities of adipocytes suggest a link between mitochondrial damage, the use of NRTIs, and lipoatrophy in HIV-infected patients.
Design Randomized, open-label 24-week study. Setting Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001. Participants A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy. Intervention Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57). Main Outcome Measures The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels. Results There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh ( P = .01), arm ( P <.001), and abdominal ( P = .001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity ( r = -0.06; P = .53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%). Conclusions In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.
Rosiglitazone increases subcutaneous fat in type 2 diabetic patients and reverses the block of adipocyte differentiation induced by HAART in vitro
Background Lipodystrophy commonly complicates antiretroviral therapy of HIV-1 infection. Thiazolidinediones such as rosiglitazone promote subcutaneous fat growth in type 2 diabetics and adults with congenital lipodystrophy, and can prevent HIV-1 protease inhibitor toxicity to adipocytes in vitro. We postulated that rosiglitazone would improve HIV lipoatrophy. Methods 108 HIV-1-infected lipoatrophic adults on antiretroviral therapy were randomised to rosiglitazone 4 mg twice daily (n=53) or matching placebo (n=55) for 48 weeks. The study had 80% power to detect a 0·5 kg difference in changes in limb fat (using dual-energy X-ray absorptiometry) between groups at week 48 by intention-to-treat analysis, and a 0·7 kg difference within each protease inhibitor stratum. Findings Limb fat increased by 0·14 kg in the rosiglitazone group and 0·18 kg in the placebo group (mean difference –0·04 kg [95%CI –0·29 to 0·21]; p=0·74 by t test), with three participants (one on rosiglitazone and two controls), lost to follow-up. Rosiglitazone had no significant benefit on any other measure of lipodystrophy, despite large relative increases in plasma adiponectin (4·2 mmol/L [102%]; p<0·0001) and in three markers of insulin sensitivity (p=0·01 to 0·02). Six participants ceased study drug in each group, four participants (three on rosiglitazone and one control) for related adverse events. The main adverse effects, which seem to be almost unique to this population, were asymptomatic hypertriglyceridaemia (mean relative increase 0·9 mmol/L at week 48; p=0·04) and hyper-cholesterolaemia (1·5 mmol/L; p=0·001). Interpretation Rosiglitazone for 48 weeks did not improve lipoatrophy in HIV-1-infected adults receiving antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary to prevent lipoatrophy.
Before & after Examples from VEGA Clinical change after PLA injections between baseline and week 96, after five and four sessions of injections, for patient 1 and patient 2 respectively. (a-d) Patient 1, at day 0 (a, c) and week 96 (b, d)
Methods: The goal of this open-label, single-arm, pilot study was to evaluate the efficacy and safety of facial injections of poly-L-lactic acid (PLA) (New-Fill)® in HIV-infected patients with severe facial lipoatrophy. Patients received four sets of injection at day 0 and then every 2 weeks for 6 weeks. Patients were evaluated by clinical examination, facial ultrasonography, and photography at screening and at weeks 6, 24, 48, 72, and 96. Results: Fifty patients were enrolled. At entry, the median facial fat thickness was equal to zero (range, 0.0-2.1 mm). The median total cutaneous thickness (TCT) increased significantly from baseline : +5.1 mm (range, 2.2-8.6 mm) at week 6, +6.4 mm (range, 3.1-9.1 mm) at week 24, +7.2 mm (range, 4.2-9.6 mm) at week 48, +7.2 mm (range, 3.5-9.6 mm) at week 72 and +6.8 mm (range, 3.9-10.1 mm) at week 96 ( P < 0.001). The proportion of patients with TCT > 10 mm was observed in 19% at week 6, 41% at week 24, 61% at week 48, 52% at week 72 and 43% at week 96. In 22 (44%) patients, palpable but non-visible subcutaneous micronodules were observed with a spontaneous resolution in six patients at week 96. Conclusion: The benefit of PLA for the correction of the facial lipoatrophy in HIV-infected patients was clearly demonstrated, with an evident aesthetic and quality of life improvement. The efficacy, safety profile, and the simplicity of the injection schedule of PLA make this filling material a potentially attractive treatment. The first European data was submitted by Amard and Saint Marc in September of 2000. Twenty-six lipoatrophy patients were treated with New Fill. Ultrasound measurement was used to measure dermal thickness. A 151% increase in dermal thickness was found at 3 months, 196% at 6 months, and 131% at 54 weeks.[ 4 ] A 96-week study was presented at the 10th Conference for Retroviral and Opportunistic Infection in Boston in February of 2003. Researchers from this VEGA study presented the results of 50 HIV-positive patients after receiving Sculptra for correction of facial lipodystrophy. Change in dermal thickness was evaluated using ultrasound and color Doppler preformed by the same trained radiologists. They found a threefold increase in dermal thickness, which was sustained at 72 and 96 weeks.[ 5 ] Another study presented by Lafaurie from St Louis Hospital in Paris, France involved treating 40 patients with lipodystrophy. In this study, the product was diluted with 3 mL of sterile water and the patients were treated with 150 mg per cheek every 15 days. Efficacy was evaluated at 2 months and after 6 months utilizing photos analyzed by digital surface photogrammetry software. Results showed a mean increase of dermal thickness of 2.4 mm after two injections. Results were maintained at 2 and 6 months.[ 6 ] The Chelsea Westminster study was done in London. A total of 30 patients with lipoatrophy were treated with Sculptra. These patients were randomized into two groups. The first group was treated every 2 weeks for a total of three treatments. The second group had no treatment for the first 12 weeks and then received three treatments as well at weeks 12, 14, and 16, thus acting as a negative control. Both groups were evaluated at weeks 0, 12, and 24, utilizing ultrasound and serial photographs. Statistically significant increases in dermal thickness were noted in all patients with maintenance of clinically significant results to 2 years.[ 7 ] In July 2002 an investigational device exemption (IDE) was submitted and accepted from Blue Pacific Aesthetic Medical Group in Hermosa Beach, California.[ 7 ] We enrolled 100 patients who received one to six treatments spaced 3 weeks apart. Caliper skin thickness was used to measure changes in transcutaneous thickness. Baseline laboratory values were taken and repeated every 3, 6, and 12 months to verify no change in lactic acid level. A well-being questionnaire was filled out prior to treatment, at the end of treatment, and at 6 and 12 months.[ 8 ] As of October 2004, 100 patients were enrolled in the study, 99 completed treatment, 76 had completed the 6-month follow-up, and 54 completed the 12-month follow-up. A mean average of 57.8% increase in transcutaneous thickness was noted at the end of the study. At 6 months the increase in total cutaneous thickness (TCT) was 53.5% and this was shown to be maintained at 1 year with a 54.9% increase in thickness. Actual measurements were: initially (prior to treatment), 7.1 mm; end of treatment, 11.2 mm; 6-month follow-up, 10.9 mm; and 1 year, 11.0 mm. These results showed the augmentation not only held at 1 year but actually increased. Our study was used to establish clinical safety with Sculptra in submission to the FDA. There was one additional U.S. study done by Peter Engelhart and colleagues in Florida. This was APEX 002, which was an investigator-initiated study. His results on efficacy and safety were similar to ours.[ 9 ] In all studies, there were no serious adverse results. Although bruising and other injection related complications are always a possibility, the only device-related complication was that of subcutaneous nodules. These nodules are defined as being less than 5 mm, not visible but palpable. In our study nodule formation occurred with an incident of 9.2%. The average onset was 6 months and 46% spontaneously resolved (Tables [ 1 ] and [ 2 ]). If spontaneous resolution does not occur, a subcision with a 25-gauge needle, followed by localized steroid or saline injection, may improve resolution. This may be repeated weekly and used in conjunction with massage. As a final treatment to any resilient nodules, a 5FU and steroid combination in very small quantities may be injected locally into the nodule. This may be repeated monthly as needed. Complete resolution may take 5 to 8 months. REFERENCES 1 Brady JM, Cutright DE, Miller RA, Barristone GC. Resorption rate, route, route of elimination, and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat. J Biomed Mater Res 1973; 7: 155-166 2 Cutright DE, Perez B, Beasley JD, Larson WJ, Posey WR. Degradation rates of polymers and copolymers of polylactic and polyglycolic acids. Oral Surg Oral Med Oral Pathol 1974; 37: 142-152 3 Sattler G. Long-lasting results with polylactic acid. Derm 2003; 9: 422-423 4 Amard & Saint Marc. Polylactic acid in the treatment of HIV-associated lipoatrophy. Second Lipodystrophy Workshop, Toronto, Canada: September 2000 5 Mest DM, Humble G. Hermosa Beach, California, Current IDE#G020113. 6 Lafaurie M. Dolivio, St. Louis Hospital, Paris, FranceTreatment of lipoatrophy with injections of polylactic acid. Tenth Conference for Retrovirus and Opportunistic Infection. February 2003 7 Moyle GJ, Lysakova L, Brown S. A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection. HIV Med 2004; 5: 82-87 8 Mest D, Humble G. Safety and efficiency of intradermal poly-L-lactic acid (Sculptura) injections for patients with HIV associated facial lipoatrophy. Antivir Ther 2004; 9: L36 9 Engelhard P, Knies M. Safety and efficacy of New-Fill® (polylactic acid) in the treatment of HIV-associated lipoatrophy of the face (HALF). XIV International AIDS Conference Barcelona, Spain: July 7-12, 2002
Studies cited in Schambelan et al: 1. Grunfeld C et al. J Clin Endocr Metab 1992;74:1045-52. 2. Zangerle R et al. JAIDS 1994;7:1149-56. 3. Feingold KR et al. J Clin Endocr Metab 1993;76:1423-7. 4. Grunfeld C et al. Am J Med 1989;86:27-31. 5. Noor MA et al. AIDS 2001;15:F11-F18. 6. 9th CROI, February 2001. 7. Echevarria KL et al. Ann Pharmacother 1999;33:859-63. 8. Periard D et al. Circulation 1999;100:700-5. 9. Carr A et al. Lancet 1999;353:2093-9. 10. Mulligan K et al. JAIDS 2000;23:35-43.
Figure 1. Incidence of Myocardial Infarction According to the Duration of Exposure to Combination Antiretroviral Therapy. The incidence of primary events was assessed beginning at base line according to the cumulative duration of combination antiretroviral therapy since the initiation of therapy, stratified in one-year intervals from the initiation of therapy to four years, more than four years of exposure, and no exposure. The rate of myocardial infarction was generally lower among the patients not exposed to combination antiretroviral therapy than in any of the treated groups. The untreated patients had, a priori, a lower risk of myocardial infarction than the treated patients.26 As compared with the rate of myocardial infarction among the patients treated for less than one year, the univariable relative rate among the patients with no exposure to therapy was 0.24 (95 percent confidence interval, 0.07 to 0.89); among those with one to less than two years of exposure, 1.34 (95 percent confidence interval, 0.58 to 3.10); among those with two to less than three years of exposure, 1.73 (95 percent confidence interval, 0.80 to 3.76); among those with three to four years of exposure, 1.98 (95 percent confidence interval, 0.94 to 4.15); and among those with more than four years of exposure, 2.55 (95 percent confidence interval, 1.25 to 5.20) (P for trend <0.001). The vertical bars represent the 95 percent confidence intervals.
1 Investigators from the HIV Outpatient Study (HOPS) group, an ongoing CDC-supported study at 10 sites around the United States, examined the incidence of and risk factors for myocardial infarction in their cohort since 1993. [1] They compared data from patients taking protease inhibitors (PIs) and those not taking PIs. A total of 13 of the 3013 persons taking PIs developed a myocardial infarction, angina, or cerebrovascular accident, for an incidence of 1.2 per 1000 person-years, compared with 2 of 2665 patients not taking PIs (0.5/1000 person-years). The association with PIs remained even when other cardiovascular risk factors were taken into account. However, most incidents of cardiovascular disease occurred in persons with known risk factors. Holmberg S, Moorman AC, Tong T, et al. Protease inhibitor drug use and myocardial infarction in ambulatory HIV-infected patients. Program and abstracts of the 39th Annual Meeting of the Infectious Diseases Society of America; October 25-28, 2001; San Francisco, California. Abstract 941.
Nonetheless, we should not ignore the hyperlipidemia associated with HIV. Treatment may be difficult, however, as noted by Dr. Judith Aberg,[3] who presented updated information from ACTG 5087, a randomized trial of pravastatin vs fenofibrate. This study was halted by its data and safety monitoring board because fewer than 5% of patients responded to either drug alone, when response was defined as a composite end point of reductions in low-density lipoprotein (LDL) cholesterol and triglycerides levels. At this meeting, Dr. Aberg reported the initial results on 136 patients who, having failed either pravastatin or fenofibrate as monotherapy, then received 12 weeks of combination therapy. Overall, only 10% of patients responded. Of interest, better responses were seen among patients who had received prior fenofibrate monotherapy before starting both drugs, compared with those who started with pravastatin monotherapy. Only 3 subjects (5%) on dual therapy who initially started on pravastatin achieved the composite goal, compared with 10 subjects (16%) on dual therapy who initially started on fenofibrate. Overall, there were some differences between the drugs. Pravastatin appeared to be the more effective at lowering LDL cholesterol, while patients who received fenofibrate had larger increases in high-density lipoprotein (HDL) cholesterol and decreases in triglycerides. Combination therapy was well tolerated through 12 weeks of treatment: only 4 patients discontinued treatment and there were no cases of hepatitis or rhabdomyolysis. However, as Dr. Aberg pointed out, the overall results in terms of correction of hyperlipidemia were poor, suggesting that alternative strategies will be needed.
Objective: To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls. Design: Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003. Methods: Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 1/[log10(glucose) þ log10 (insulin)] and fasting hyperinsulinemia (insulin > 15 mU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus. Results: Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.13) and a lower QUICKI (0.04; 95% CI, 0.07 to 0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2–1.3). Conclusions: Fasting surrogate markers suggest increased insulin resistance in HIVinfected men, which is related to cumulative NRTI exposure. 2005 Lippincott Williams & Wilkins AIDS 2005, 19 : 1375–1383
7,219 HIV-infected subjects and 2,792,971 uninfected controls; over 7 million patient-years of followup. Used MediCal claims database. Overall incidence rate of 10.7/100 patient-years for those w/ HIV infxn, compared to 2.9/100 patient-years for those w/o HIV infxn, yielding a RR of 3.32!
Carr A, Miller J, Eisman JA, Cooper DA. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS. 2001 Apr 13;15(6):703-9. Huang JS, Rietschel P, Hadigan CM, Rosenthal DI, Grinspoon S. Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy. AIDS. 2001 May 25;15(8):975-82. McDermott AY, Shevitz A, Knox T, Roubenoff R, Kehayias J, Gorbach S. Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women. Am J Clin Nutr 2001 Nov;74(5):679-86 Knobel H, Guelar A, Vallecillo G, Nogues X, Diez A. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS 2001 Apr 13;15(6):807-8 Nolan D, Upton R, McKinnon E, John M, James I, Adler B, Roff G, Vasikaran S, Mallal S . Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir. AIDS 2001 Jul 6;15(10):1275-80 Gold J, Pocock N, Li Y; Albion St Centre Osteoporosis and HIV Study group. Bone mineral density abnormalities in patients with HIV infection. J Acquir Immune Defic Syndr. 2002 May 1;30(1):131-2. Mondy K et al. CID 2003;36:482-90. Arnsten JH et al, 10th CROI, Boston 2003, Abstract 103
Background: Osteonecrosis has been reported to occur occasionally among HIV-infected patients. The diagnosis of symptomatic osteonecrosis of the hip in two of the authors' patients, together with reports from community physicians, raised a concern that the prevalence of osteonecrosis is increasing. Objective: To determine the prevalence of osteonecrosis of the hip in asymptomatic HIV-infected patients and to identify potential risk factors associated with osteonecrosis. Design: Survey and comparison study. Setting: The Clinical Center of the U.S. National Institutes of Health. Participants: 339 asymptomatic HIV-infected adults (of 364 asked to participate) and 118 age- and sex-matched HIV-negative volunteers enrolled between 1 June and 15 December 1999. Measurements: Osteonecrosis of the hip, as documented by magnetic resonance imaging. Data from clinic records and a patient questionnaire administered before magnetic resonance imaging were used in an analysis of risk factors. A subset of patients was evaluated for hypercoagulable state. Results: Fifteen (4.4% [95% CI, 2.5% to 7.2%]) of 339 HIV-infected participants had osteonecrosis lesions on magnetic resonance imaging, and no HIV-negative participants had similar lesions. Among HIV-infected participants, osteonecrosis occurred more frequently in those who used systemic corticosteroids, lipid-lowering agents, or testosterone; those who exercised routinely by bodybuilding; and those who had detectable levels of anticardiolipin antibodies. Conclusions: Patients infected with HIV have an unexpectedly high occurrence of osteonecrosis of the hip. Although screening asymptomatic patients is not warranted, HIV-infected patients with persistent groin or hip pain should be evaluated for this debilitating complication.