8/10/2017. HIV UPDATE 2017 David M Stein DO, FACOI

Transcription

1 HIV UPDATE 2017 David M Stein DO, FACOI 1

2 Current US HIV data 1.1 million HIV positive 1 out of 7 positive are unaware of their status Highest risk in Gay and Bisexual men, young African American men 2

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4 New HIV infections among men and women (aged years), global, Women aged years Men aged years Source: UNAIDS 2016 estimates. Number of people living with HIV (aged 50 years and over), high-income countries and low- and middle-income countries, and projected to 2020 Number (million) People living with HIV (aged 50 years and over) in high-income countries People living with HIV (aged 50 years and over) in lowand middle-income countries Source: UNAIDS 2016 estimates. Note: Projections are based on an assumption that scale up of antiretroviral treatment will reach 81% coverage of all people living with HIV by Country income classifications are from

5 Critical risks, services and strategic information for people living with HIV aged 50 and over Worldwide impact New HIV infections 2.1 million newly infected Adults are stable at million new but children new positives have declined by 50% Deaths from HIV have declined 45% since 2005 Attacking HIV across the globe Target : in the HIV world 90% aware of status 90% on ARV treatment 90% achieved undetectable level 5

6 Success in America has been due to more aggressive testing and treatment Reducing the numbers of unknown status and increasing treatment availability Returning HIV as a differential to all unusual cases New HIV testing Paradigm faster and more accurate No longer ELISA then Western Blot Now initial HIV p 24 Antigen test if negative no next step if positive then obtain an immunoassay that differentiates HIV 1 from HIV 2 antibodies. These assays produce results faster than the previously recommended Western blot and distinguish between HIV 1 and HIV 2, which the previously recommended Western blot cannot do. In the face of a positive result on the initial immunoassay but negative or indeterminate result on the antibody differentiation assay, the CDC advises proceeding to HIV 1 nucleic acid testing for resolution Adopting the new recommendations will lead to HIV diagnosis as much as 3 to 4 weeks sooner than the previous testing approach, the CDC says. 6

7 HIV prevention Biomedical Interventions Behavioral Interventions Biomedical Preventions PrEP prophylactic pre exposure medication Post Exposure Prophylaxis Short term after exposure Medication HAART to decrease viral load Barrier Contraceptives Treating STD to decrease ease of infection Male circumcision successful in Africa Universal Precautions Interrupting Mother to Child Transmission PrEP 75% reduction in transmission if participant takes meds faithfully Best candidates highest risk of transmission in M S M increased risk HIV positive partner Recent or frequent STI High number of partners Inconsistent/no condom use Commercial sex work 7

8 Before starting PrEP Negative HIV No evidence of acute infection Normal renal function* No interfering medications Know HEP B and general vaccine status Transgender individuals are at very high risk Often engaging in high risk behaviors Already marginalized from many health and social agencies Heterosexual women and men with positive partner, recent STI, high number of sex partners, inconsistent use of condoms, commercial sex work 8

9 PrEP candidate IVDA Sharing with known HIV + Sharing injection equipment Question if encourages risky behavior to continue Difference between PrEP and post exposure Prophylaxis High risk exposure that was unexpected ( needle stick, rape, condom failure) Begin as soon as possible 4 6 weeks of therapy triple drug therapy Behavioral Interventions Honest dialogue with patients regarding risky behaviors Educate all patients no clear at risk group Address attitudes and beliefs especially in young, minority and marginalized patients 9

10 Current treatment guidelines T achieve less toxicity changes have been made in drugs of choice 10

11 When to start Start early, as soon as you are comfortable to start and they are ready Study shows better results when therapy initiated rapidly better message on importance of why we start quickly Simplify regimens Need multiple drug regimens for success (3 or 4 drug regimens) but one pill once a day has better compliance Life expectancy changes A 20 year old who began treatment any time since 2008, now has an expected lifespan, about 78 years, approaching that of an uninfected person, said a study in The Lancet HIV. People who started taking antiretroviral therapy(art) in 2008 or thereafter lived longer, healthier lives than those who started treatment in earlier years This was likely because modern drugs have fewer toxic side effects, there are now more options for people with a drug resistant HIV strain, and better treatment of other infections and conditions. 11

12 HIV-positive people will now live into old age, clinicians are screening for and treating comorbidities (diseases on top of HIV) more aggressively, These included heart disease, hepatitis C and cancer. HIV and OPIOID Epidemic In many areas the Opioid epidemic is reversing the success of lowering HIV rates 12

13 It has been shown that needle exchange programs do work to reduce new infections but there is no consistency in laws across country and there is even intrastate variability Overcoming Barriers to prevention and cure Many researchers believe that the best chance to eliminate HIV is to reactivate the virus in reservoir cells, which would then make it susceptible to killing by ART Intense research into these shock and kill approaches is being undertaken and several classes of latency-reversing agents (LRAs) are being assessed Histone deacetylase (HDAC) inhibitors, PKC agonists, a PTEN inhibitor and TLR agonists are showing potential, but it has become apparent that one LRA class alone will not be able to reactivate 100% of latent HIV More effective latency-reversing interventions and combinations of LRAs and/or LRAs with immune modulation are needed to optimize potency AL Landay PhD 13

14 The block and lock strategy Hypothetical approaches to a functional HIV cure (1) After HIV-1 infection, there is a sharp increase of viral load in circulating plasma of infected individuals. (2) The viral load sharply decreases during ART, but episodes of detectable viremia blips are observed. HIV-1 remains latent in most infected individuals, but if ART is discontinued (3), there is an immediate rebound of virus. (4) HIV Tat inhibitor didehydro-cortistatin A (dca) in combination with ARVs, potently inhibits HIV-1 transcription and mediates deep latency in cell line models and primary human CD4+ T cells, even after treatment cessation. Mousseau et al., mbio, 2015 Susana Valente s group Therapeutic Vaccines to Augment HIV Specific Responses Old Therapeutic Vaccine Targets Canary Pox, Ad5, Plasmid DNA New Therapeutic Vaccine Targets CMV, AD26, Dendritic cells, MVA HIV Cons D Barouch et al, Science July 11, 2014 Expect in 2017 vaccine SAV001 will enter phase 2 study. Initial experience showed stimulation of broadly neutralising antibodies that attack multiple sub types of HIV virus Vaccine is derived from an inactivated and killed HIV 1 virus 14

15 Current vaccine trials include the HVTN 702 trial which is ongoing Most recent completed was the RV144 trial(2009) with only a 31% efficacy A small trial in Spain had 5 individuals who could maintain an undetectable viral load off medication with the IrsiCaixa Research center vaccine(2017) Inovio Pharmaceuticals PENNVAX GP vaccine demonstrated 100% cellular response and 90% demonstarted an env specific antibody response(2017) reported as HVTN 098 trial What to watch for in HIV patients Opportunistic Infections HIV related Cancers Coronary artery Disease Hepatitis Mental Health Concerns Addiction Concerns Tuberculosis Hyperlipidemia STDs Nutritional Risks Opportunistic Infections Unusual presentations of bacterial, viral, parasitic and fungal infections Rapid progression of disease Usually associated with reduced CD4 counts Most common: Pneumo. Jirovecki Pneumina(PCP); CMV infections of multiple different sites; Mycob. Avium Complex; Toxoplasmosis and Histoplasmosis Infections ( area specific) 15

16 Cancers Kaposi Sarcoma related to HHV 8 and HIV Non Hodgkins Lymphoma common with long term survival and HIV Rectal and Cervical Cancers type of sexual act Cardiac Risk Higher incidence of elevated lipids and CAD with diagnosis and treatment Related to living longer and side effects of Meds HIV is a source of chronic inflammation and directly decreases HDL and raises Triglycerides Behavioral Concerns Higher percentage of individuals with depression and addiction as compared to non HIV population Many positive people consider themselves to be marginalized people 16

17 Hepatitis and STDs Nature of routes of infection associated with increase rates of Hep B and C Higher incidence of STD exposure ( which increases risk of transmission) Nutritional Risks Wasting syndrome chronic inflammation and poor absorption Chronic diarrhea Emotional and financial concerns ** Thank You QUESTIONS? And then LUNCH 17