HIV Update For the Internist

HIV Update For the Internist

Disclosures I declare that I have received no incentives, financial or otherwise, from pharmaceutical or biomedical companies relevant to the content of this talk. As an Infectious Disease consultant and General Internist in the Northwest Territories, HIV medicine is only one of my many clinical activities!

Objectives 1. In the context of the Canadian landscape in 2014, participants will be able to summarize a shifting HIV epidemiology 2. Participants will be able to discuss HIV infection as a cause of coronary artery disease 3. Confronted with a patient with newly diagnosed HIV infection, participants will be able to describe considerations regarding assessment and prognostication 4. Participants will understand the rationale behind newest HIV treatment recommendations, and apply these broad principles to a typical case

Case A 45 year old heterosexual Canadian man was recently diagnosed with HIV at an STI clinic after a number of unprotected sexual contacts. He denied homosexual contacts, IVDU, or blood transfusions in the past, does not work in health care. He is asymptomatic and in good health, with a CD4 count of 520 (28%) and a viral load of 150,000. A virtual phenotypic analysis of his viral genome reveals no genetic mutations predictive of treatment resistance. He recently initiated a new monogamous relationship with an HIV- partner.

Questions How common is heterosexual transmission of HIV? His father had an MI at age 46, he wonders how this impacts his risk of CAD What is the natural history of his disease if left untreated? If treated starting today? How should he be managed according to current guideline recommendations, and why?

UPDATE: EPIDEMIOLOGY OF HIV IN CANADA

The Current Story 71,300 Canadians with HIV at the end of 2011 An estimated 25% undiagnosed 3,175 new cases in 2011, a stable incidence since 2008 IV drug is an increasingly uncommon risk factor Only accounted for 14% of new infections in 2011 Aboriginals and persons from countries where HIV is endemic are still over-represented HIV infection rate 3.5 and 9 times more common 2011 Estimates of HIV prevalence and incidence in Canada. PHAC

New HIV Infections By Exposure 2011 Estimates of HIV prevalence and incidence in Canada. PHAC

Prevalence of HIV 2011 Estimates of HIV prevalence and incidence in Canada. PHAC

New Cases per 100,000 Pop n in 2012 Source: Public Health Agency of Canada (http://www.phac-aspc.gc.ca) HIV and AIDS in Canada: Surveillance Report to December 31, 2012

Proportion of Persons Living with HIV Over Age 50, By Region Source: UN AIDS, HIV and Aging Special Report (www.unaids.org )

Review The Incidence of HIV in Canada over the last 10 years: A. Is increasing B. Is decreasing C. Is stable

HIV AS A CAUSE OF CORONARY ARTERY DISEASE

HIV and CAD Antivirals have dramatically lowered the risk of AIDS-related mortality since 1996 Other hidden costs of infection in an aging HIVinfected population have been revealed HIV-infected patients consistently found to have an increased hazard ratio for MI or CAD (range, 1.4-2.9), compared to non-infected patients Triant VA, Epidemiology of cardiovascular disease in HIV patients. Rev Cardiovasc Med. 2014; 15(0 1): S1 S8.

Aetiology of CAD in HIV Patients Traditional Risk Factors Are Important Age Cholesterol Hypertriglyceridemia and low HDL Smoking Hypertension, diabetes increasingly common Persistent elevation in risk of CAD after adjusting for these risk factors

Aetiology of CAD in HIV Patients Traditional Risk Factors Are Important HIV-Related Risk Factors Antiviral medications Protease inhibitors Abacavir HIV-associated inflammatory state Highest risk with individuals with the greatest disease activity (highest viral load, lowest CD4) Treatment interruption El-Sadr WM et al. Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med. 2006;355(22):2283.

Mechanisms of HIV-Associated CAD Elevated soluble and cellular markers of inflammation Endothelial dysfunction Altered coagulation

Review The increased risk of CAD in HIV infected patients is mediated by: A. Immune activation B. Traditional CAD risk factors C. Antiviral-associated dyslipidemia D. All of the above

HIV AND PROGNOSIS

HIV Natural History Left untreated, median survival time is 8-10 years ( Porter et al, AIDS 1999)

Prognosis Without Antiviral Therapy Risk of AIDS Indicator Illness In a Cohort of 1604 Men Enrolled in the Multicentre AIDS Cohort Study 1984-85 (Mellors et al, Ann Int Med 1997)

Life With HIV in 2014 Current antiviral therapies have decreased mortality and increased life expectancy UK Collaborative Cohort Study (CHIC) Registry data: 22,876 patients with HIV starting therapy between 1996 and 2008 Calculated life expectancy (LE) at age 20: 1996 to 1999: 30 more years 2006 to 2008: 45.8 more years May et al, Brit Med J 2011 Average LE in general male and female populations: 57.8 & 61.6

Improvements in Antiviral Therapy Over the Last 15 Years Highly Active Antiretroviral Therapy first introduced in 1996 High pill burden, frequent and serious side effects, low genetic barrier to resistance Today s antiviral therapies Much easier to swallow

Treatment Success is Increasing! Proportion of persons started on antiviral therapy who achieved an undetectable viral load Gill et al, Clin Infect Dis 2010

New Diagnosis of HIV: Getting Over The Hump In a registry-based case-control study in England The age-matched proportion of HIV+ people who died decreased 3-fold in the last 10 years Age-matched mortality for HIV+ individuals still 5- fold higher in comparison to HIV- Difference in mortality greatest in younger groups Why? Simmons et al, HIV Medicine 2013

New Diagnosis of HIV: Getting Over The Hump Late diagnosis major risk factor for increased mortality (OR 10.55) 50% of deaths in HIV+ persons were within 4 months of diagnosis Leading causes of death PJP and bacterial pneumonia non-hodgkin s lymphoma TB Kaposi s sarcoma PML Toxoplasmosis cryptosporidiosis Simmons et al, HIV Medicine 2013

Ongoing Clinical Challenges in HIV Low CD4 count at time of antiviral initiation remains the major predictor of excess mortality in HIV Early diagnosis is the key! Non-AIDS associated now dominate cause of death in HIV infected individuals after first year on therapy Addictions Cirrhosis (HCV) Chronic inflammatory conditions including CAD

HIV and Diabetes Mellitus An Apt Comparison?

Review Mortality in HIV has shifted in the pasts 15 years. Grouped together, the leading causes of death in persons with HIV is now: A. Cardiovascular disease B. Non-AIDS related malignancies C. Liver disease D. Opportunistic infections and other AIDS-defining illnesses (including NHL)

TREATMENT

HIV in 2014: Keys to Management Early diagnosis Early linkage and retention to care Early antiviral treatment

HPTN 052: The Game Changer

HPTN 052 1763 serodiscordant couples across 9 countries and 4 continents 54% from Sub-Saharan Africa HIV+ partner had CD4 count 350-550 cells/ul Randomized to immediate vs. delayed therapy (CD4 cells <250 or first OI) Primary endpoint: linked transmission of HIV in the HIV negative partner

Of 28 genetically linked HIV transmissions, only one occurred in the immediate therapy group HPTN 052

HPTN 052 Of 28 genetically linked HIV transmissions, only one occurred in the immediate therapy group This transmission was proven to have occurred before the treated partner became virologically suppressed

Earlier Treatment: Beneficial for the PROS Decreased progression to AIDS with earlier treatment 2 recent clinical trials and 1 large cohort* Improved retention to care in observational studies inflammation? Individual? CONS Decreasing rate of return (low ARR) Treatment side effects Possible low adherence outside of clinical trials $$$ Logistics issues *Severe et al, N Engl J Med. 2010;363:257 265, Grinsztejn et al, Lancet Infect Dis. 2014 April ; 14(4): 281 290. Mocroft et al, Clin Infect Dis. 2013;57:1038 1047

Current North American Guidelines Antiviral medications recommended for treatment of all HIV infected individuals Strength of evidence increases as CD4 counts decrease, highest for CD4 <500 Also strongly recommended during pregnancy, or with HBV coinfection, HIV nephropathy Source: IAS 2014 Treatment Guidelines, www.iasusa.org

Current North American Guidelines 1 st line regimens still include 2 nucleoside reverse transcriptase inhibitor backbone combined with: Non-nucleoside reverse transcriptase inhibitor, OR An integrase strand transfer inhibitor A boosted protease inhibitor 3 first-line one pill, once daily, fixed dose combinations are available Treatment individualized and based on GART Source: IAS 2014 Treatment Guidelines, www.iasusa.org

Don t Forget! Prophylaxis against opportunistic infections is still recommended: CD4 <200 cells/ul TMP-SMX (2 nd line: dapsone) for PJP CD4 <100 cells/ul TMP-SMX (2 nd line: dapsone-pyrimethimine with leucovorin) for Toxoplasma encephalitis CD4 <50 cells/ul Azithromycin (2 nd line: rifabutin) for disseminated MAC

Review In HPTN 052, the proportion of linked HIV transmissions which were prevented by antiviral treatment in affected partners was: A. 52% B. 78% C. 88% D. 96%

Case A 45 year old heterosexual Canadian man was recently diagnosed with HIV at an STI clinic after a number of unprotected sexual contacts. He denied homosexual contacts, IVDU, or blood transfusions in the past, does not work in health care. He is asymptomatic and in good health, with a CD4 count of 520 (28%) and a viral load of 150,000. A virtual phenotypic analysis of his viral genome reveals no genetic mutations predictive of treatment resistance. He recently initiated a new monogamous relationship with an HIV- partner.

Questions How common is heterosexual transmission of HIV? His father had an MI at age 46, he wonders how this impacts his risk of CAD What is the natural history of his disease if left untreated? If treated starting today? How should he be managed according to current guideline recommendations, and why?

Thank You!!!