HIV Update 2013
Ellen M. Tedaldi, M.D.
Professor of Medicine
Director, Temple Comprehensive HIV Program


Epidemiology-local



Screening and Diagnosis



Evaluation of the HIV+ patient



Treatment updates



Ophthalmolo...
•Rate of HIV 5x
national average
•Heterosexuals
55% of new
infections
•New infections
•15% 13-24
y/o
•51% 25-45
y/o
•34% >...
Demographics of HIV in Philadelphia
HIV IN AFRICA and SELECTED US SITES
Mortality by Race and Payer
Disparities
Palella, AIDS, 2011
Communities in Crisis: Is There a
Generalized HIV Epidemic in Impoverished
Urban Areas of the United States?

Denning P, I...


Epidemiology-local



Screening and Diagnosis



Evaluation of the HIV+ patient



Treatment updates



Ophthalmolo...
Screening/diagnosis
2011 PA law
changed-no written
consent
 2013 USPSTF- All
adults 15-65 to be
tested for HIV
 Rapid te...








Rapid testing (similar
to ELISA) need
confirmation with
Western Blot
Traditional HIV Test
has ELISA/Western
Bl...
Reactivity of FDA approved assays for HIV-1 compared to WB

The Future of HIV Testing.
Branson, Bernard
JAIDS Journal of A...
The Future of HIV Testing.
Branson, Bernard
JAIDS Journal of Acquired Immune Deficiency
Syndromes. 55 Supplement 2, The HI...
HIV PATHOGENESIS
Time course of HIV Infection
Acute Retroviral Syndrome:
Common Signs and Symptoms













Fever
Lymphadenopathy
Pharyngitis
Rash
Myalg...
Goals of Treatment
 Reduce

HIV-related morbidity;
prolong duration and quality of
survival
 Restore and/or preserve imm...


Epidemiology-local



Screening and Diagnosis



Evaluation of the HIV+ patient



Treatment updates



Ophthalmolo...







History
Physical: attention
to skin,
lymphadenopathy,
liver, neuro
Women: baseline
PAP and
GC/Chlamydia
Men:
GC...









CBC
Chemistry
Hepatitis B and C
and A testing
RPR
CMV
Lipid Profile
Toxoplasma
Antibody





Confirm EL...
Use of CD4 Cell Levels to
Guide Therapy Decisions


CD4 count
◦ The major indicator of immune function
◦ Most recent CD4 ...
Use of HIV RNA Levels to
Guide Therapy Decisions (2)


RNA monitoring
◦ Check at baseline (x 2)
◦ Immediately before init...
Differences in viral Load: Women v. Men:
Regression Model Adjusted for Race, Country
and History of AIDS
0.25

Male-Female...
•Genotype &
Phenotype
•Generally need at
least 1000 copies of
virus to do test
•Done at baseline on
all
•Reliable when
pat...
Vaccinations:










Influenza
Pneumovax* 13, 23
PPD * 5 mm,
Hepatitis B
Hepatitis A
Tetanus/Tdap
HPV
AVOID: MM...


If CD4 under 200 cells/mm3, eye exam to
evaluate for CMV, HIV retinopathy.



If CMV present, role of measuring CMV
vi...
Time course of HIV Infection
When to Start?

CD4+ =200

CD4 = 500

CD4 = 350
When to Start ART
Exact CD4 count at which to initiate therapy
not known, but evidence points to starting
at higher counts...
Consider Deferral of ART


Clinical or personal factors may support
deferral of ART
◦ If CD4 count is low, deferral shoul...
Potential Benefits of Early
Therapy
◦ Untreated HIV may be associated with
development of AIDS and non-AIDSdefining condit...
Potential Benefits of Early
Therapy


Potential decrease in risk of many
complications, including:
◦
◦
◦
◦
◦
◦

HIV-assoc...
Potential Benefits of Early
Therapy (3)



Prevention of sexual and bloodborne
transmission of HIV
Prevention of mother-...
A New Paradigm:
The Broader Spectrum of HIV Disease
Ongoing Morbidity from HIV
1000
800
600
CD4+
cells
400

Early Opportun...
Considerations for Initial Regimen of
Highly Active Antiretroviral Therapy
(HAART)
Underlying
Conditions

Lifestyle
Dosing...
Initial Assessment: PATHS









Assess for
Psychological
status
Assess for
Adherence barriers
Assess for
Treatment...
Therapy is forever
 Adherence must be over 90%
 Retention in care is critical for long term
success.


Principles of Hi...
Targets of HIV Therapy
Integrase Inhibitors
Entry
Inhibitors:
Fusion, CD4, CCR5
CXCR4

Nucleus

RNA
Protease

HIV

Reverse...
Classes of ART
Nucleoside Reverse
Transcriptase Inhibitors

Non-nucleoside Reverse
Transcriptase Inhibitors
Protease Inhib...
Current ARV
Medications
NRTI

PI

 Abacavir (ABC)
 Didanosine (ddI)
 Emtricitabine (FTC)
 Lamivudine (3TC)
 Stavudine...
Initial Regimens: Preferred
NNRTI based

EFV/TDF/FTC1,2

PI based

ATV/r + TDF/FTC²
DRV/r (QD) + TDF/FTC²

II based

R...
NNRTI

Integrase

Protease

The visual preferred therapies
Viral Load Testing




Viral Load and Progression of
Disease

Type of test ordered:
real time PCR
Lower limit of
detect...
Actually < 20
copies

Goal of Therapy
Treatment-Experienced
Patients:
ART Failure


Virologic failure:
◦ HIV RNA >400 copies/mL after 24 weeks, >50
copies/mL a...
Mortality and HAART Use Over Time -- All HOPS Patients
Updated as of 2Q2013
16

100
90
80

12
70
10
8

D eath P er 10 0 P ...
HIV treatment cascade
Predictors of Inadequate
Adherence












Regimen complexity and pill burden
Low literacy level
Active drug ...






Emotional and
practical supports
Convenience of
regimen
Understanding of
the importance of
adherence
Belief in e...
Prevention of Opportunistic
Infections
CD4 < 200
cells/mm3
 Pneumocystis
juroveci
 Toxoplasmosis


CD4 < 50
cells/mm3
...




Women: over age
45 with risks for CV
disease (USPSTF)

AGES 14-24

Women with HIV
qualify
◦ Low HDL
◦ High LDL
◦ Hig...


New onset or worsening of
symptoms of an infection or
inflammatory condition after
initiation of antiretroviral
therapy...
Case Definition:
• A paradoxical deterioration in clinical status after
initiating highly active antiretroviral therapy
(H...
Antiretroviral Therapy Improves
Qualitative and Quantitative Immune
Defects
Immune suppression/deficiency

HIV
replicatio...
Clinical factors Associated with
IRIS
Male Sex
Lower CD4 cell count/ percentage at ART
initiation
 Higher HIV RNA at ART ...
HIV Disease Contributes to NonAIDS Events
Low CD4+
T-cell nadir
Coinfections
(hepatitis, CMV,
EBV, and HPV)

Persistent
in...










Lactic acidosis/hepatic
steatosis
Hepatotoxicity
Insulin resistance,
diabetes mellitus
Fat maldistribut...
HIV and Bone Disease
Continuous ART
associated with
greater bone loss1
 Certain ART with
higher risk e.g.
tenofovir
 Vit...
Traditional Factors Are the Biggest
Contributor to CHD in HIV
Population
Family history

Inactivity, diet

Abdominal obesi...


High levels of DDimer, CRP, IL-6
Smoking rates



Etc…..



Immune activation
HIV and Hepatitis C









Challenges of
therapy in co
infection
Accelerated course
of HCV when have
HIV
Increased ...


Epidemiology-local



Screening and Diagnosis



Evaluation of the HIV+ patient



Treatment updates



Ophthalmolo...
Retrospective studies: CMV associated
IRIS was common 18%
 Prospective studies: 63% in those with
prior CMV disease
 Imm...
Other ocular OI
 Syphilitic
 H zoster
 Molluscum
 Toxo
 Infectious
 HSV
 Pneumocystis
 Cryptococcal

CMV
 Related...
Guidelines:
 -for CD4< 50 and +
CMV PCR with
retinal lesions
consider
valganciclovir with
initiation of HAART


Continue...
Four Prevention OpportunitiesCohen et al, JCI, 2008
Cohen IAS 2008

UNEXPOSED

EXPOSED

EXPOSED

INFECTED

(precoital/coit...



PREP studies
Using antivirals to
prevent HIV in
uninfected

Pre-exposure Prophylaxis
HPTN 052
1763 discordant heterosexual couples
9 countries, 13 sites
Randomization
Immediate ART
350-550cells/uL

AZT+3TC+E...
HPTN 052: use of ART in
serodiscordant couples


Heterosexual
couples : treat
HIV+ partner
above 350 cells
compared delay...






Focus on testing, linkage and retention
New models for prevention
Treatment: more once a day regimens
Managing ...
Hiv eye update 2013
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  • cART, combination antiretroviral therapy; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HPV, human papillomavirus.
  • Hiv eye update 2013

    1. 1. HIV Update 2013 Ellen M. Tedaldi, M.D. Professor of Medicine Director, Temple Comprehensive HIV Program
    2. 2.  Epidemiology-local  Screening and Diagnosis  Evaluation of the HIV+ patient  Treatment updates  Ophthalmology connections Objectives for today
    3. 3. •Rate of HIV 5x national average •Heterosexuals 55% of new infections •New infections •15% 13-24 y/o •51% 25-45 y/o •34% > 45 y/o HIV/AIDS in Philadelphia
    4. 4. Demographics of HIV in Philadelphia
    5. 5. HIV IN AFRICA and SELECTED US SITES
    6. 6. Mortality by Race and Payer Disparities Palella, AIDS, 2011
    7. 7. Communities in Crisis: Is There a Generalized HIV Epidemic in Impoverished Urban Areas of the United States? Denning P, IAC July 2010
    8. 8.  Epidemiology-local  Screening and Diagnosis  Evaluation of the HIV+ patient  Treatment updates  Ophthalmology connections Objectives for today
    9. 9. Screening/diagnosis 2011 PA law changed-no written consent  2013 USPSTF- All adults 15-65 to be tested for HIV  Rapid testing in ER, L&D, anywhere 
    10. 10.     Rapid testing (similar to ELISA) need confirmation with Western Blot Traditional HIV Test has ELISA/Western Blot Temple: HIV antigen: +p 24 “4th generation assay-positive with 24 weeks Now rapid testing (Alere) same HIV Testing
    11. 11. Reactivity of FDA approved assays for HIV-1 compared to WB The Future of HIV Testing. Branson, Bernard JAIDS Journal of Acquired Immune Deficiency Syndromes. 55 Supplement 2, The HIV Epidemic in the United States: A Time for Action:S102-S105, December 15, 2010. DOI: 10.1097/QAI.0b013e3181fbca44 FIGURE 2 . Reactivity of FDA-approved assays for HIV-1 compared with Western blot. © 2010 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2
    12. 12. The Future of HIV Testing. Branson, Bernard JAIDS Journal of Acquired Immune Deficiency Syndromes. 55 Supplement 2, The HIV Epidemic in the United States: A Time for Action:S102-S105, December 15, 2010. DOI: 10.1097/QAI.0b013e3181fbca44 FIGURE 3 . Proposed diagnostic algorithm for HIV diagnosis. *Denotes if Ag/Ab combo test is used. © 2010 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2
    13. 13. HIV PATHOGENESIS
    14. 14. Time course of HIV Infection
    15. 15. Acute Retroviral Syndrome: Common Signs and Symptoms             Fever Lymphadenopathy Pharyngitis Rash Myalgia or arthralgia Diarrhea Headache Nausea and vomiting Hepatosplenomegaly Weight loss Thrush Neurological symptoms AETC National Resource Center, December 2009 www.aidsetc.org
    16. 16. Goals of Treatment  Reduce HIV-related morbidity; prolong duration and quality of survival  Restore and/or preserve immunologic function  Maximally and durably suppress HIV viral load  Prevent HIV transmission March 2012 16 www.aidsetc .org
    17. 17.  Epidemiology-local  Screening and Diagnosis  Evaluation of the HIV+ patient  Treatment updates  Ophthalmology connections Objectives for today
    18. 18.     History Physical: attention to skin, lymphadenopathy, liver, neuro Women: baseline PAP and GC/Chlamydia Men: GC/Chlamydia  Other factors: ◦ ◦ ◦ ◦ Disclosure Support system Partner status Psych history and current status Initial Evaluation of HIV+ Patient
    19. 19.        CBC Chemistry Hepatitis B and C and A testing RPR CMV Lipid Profile Toxoplasma Antibody    Confirm ELISA/ Western Blot CD4+ cell count “Viral Load” or HIV RNA PCR “copies” Laboratory Testing
    20. 20. Use of CD4 Cell Levels to Guide Therapy Decisions  CD4 count ◦ The major indicator of immune function ◦ Most recent CD4 count is best predictor of disease progression ◦ A key factor in decision to start ART or OI prophylaxis ◦ Important in determining response to ART  Adequate response: CD4 increase 50-150 cells/µL per year  CD4 monitoring ◦ Check at baseline (x 2) and at least every 3-6 months* * May consider every 6-12 months in clinically stable patients with sustained HIV RNA suppression and CD4 status well above threshold for opportunistic infection risk. March 2012 20 www.aidsetc.org
    21. 21. Use of HIV RNA Levels to Guide Therapy Decisions (2)  RNA monitoring ◦ Check at baseline (x 2) ◦ Immediately before initiating ART ◦ 2-4 weeks (not more than 8 weeks) after start or change of ART, then every 4-8 weeks until suppressed to <200 copies/mL ◦ Every 3-4 months with stable patients; may consider every 6 months for stable adherent patients with VL suppression >2-3 years ◦ Isolated “blips” may occur (transient low-level RNA, typically <400 copies/mL), are not thought to predict virologic failure  ACTG defines virologic failure as confirmed HIV RNA >200 copies/mL March 2012 21 www.aidsetc.org
    22. 22. Differences in viral Load: Women v. Men: Regression Model Adjusted for Race, Country and History of AIDS 0.25 Male-Female Mean Viral Load Difference (Log10 Copies/mL) 0.20 0.15 0.10 0.05 0.00 50 100 150 200 -0.05 Exact Screening CD4+ Lymphocytes (mm3) Adapted from Beatriz Grinsztejn et al. CROI 2008; abstract 672. 250
    23. 23. •Genotype & Phenotype •Generally need at least 1000 copies of virus to do test •Done at baseline on all •Reliable when patient on HIV med for virologic failure. Drug Resistance Testing
    24. 24. Vaccinations:         Influenza Pneumovax* 13, 23 PPD * 5 mm, Hepatitis B Hepatitis A Tetanus/Tdap HPV AVOID: MMR, Varicella, Herpes Zoster, and live vaccines * although have been evaluated
    25. 25.  If CD4 under 200 cells/mm3, eye exam to evaluate for CMV, HIV retinopathy.  If CMV present, role of measuring CMV viral load and prophylaxis with valganciclovir for patients at high risk?? Eye screening
    26. 26. Time course of HIV Infection
    27. 27. When to Start? CD4+ =200 CD4 = 500 CD4 = 350
    28. 28. When to Start ART Exact CD4 count at which to initiate therapy not known, but evidence points to starting at higher counts  Current recommendation: ART for all  ART for treatment and prevention  February 2013 28 ww w.ai dset c.or g
    29. 29. Consider Deferral of ART  Clinical or personal factors may support deferral of ART ◦ If CD4 count is low, deferral should be considered only in unusual situations, and with close follow-up    When there are significant barriers to adherence If co morbidities complicate or prohibit ART “Elite controllers” and long-term nonprogressors March 2012 30 ww w.ai dset c.or g
    30. 30. Potential Benefits of Early Therapy ◦ Untreated HIV may be associated with development of AIDS and non-AIDSdefining conditions  Earlier ART may prevent HIV-related endorgan damage; deferred ART may not reliably repair damage acquired earlier ◦ Increasing evidence of direct HIV effects on various end organs and indirect effects via HIVassociated inflammation ◦ End-organ damage occurs at all stages of infection February 2013 31 ww w.ai dset c.or g
    31. 31. Potential Benefits of Early Therapy  Potential decrease in risk of many complications, including: ◦ ◦ ◦ ◦ ◦ ◦ HIV-associated nephropathy Liver disease progression from hepatitis B or C Cardiovascular disease Malignancies (AIDS defining and non-AIDS defining) Neurocognitive decline Blunted immunological response owing to ART initiation at older age ◦ Persistent T-cell activation and inflammation February 2013 32 ww w.ai dset c.or g
    32. 32. Potential Benefits of Early Therapy (3)   Prevention of sexual and bloodborne transmission of HIV Prevention of mother-to-child transmission of HIV March 2012 33 ww w.ai dset c.or g
    33. 33. A New Paradigm: The Broader Spectrum of HIV Disease Ongoing Morbidity from HIV 1000 800 600 CD4+ cells 400 Early Opportunistic Infections Late Opportunistic Infections 200 0 1 Infection 2 3 4 5 6 7 8 9 10 11 12 13 14 Time in Years
    34. 34. Considerations for Initial Regimen of Highly Active Antiretroviral Therapy (HAART) Underlying Conditions Lifestyle Dosing Pill Burden Diabetes Hepatitis CV Disease Drug Interactions Initial Treatment Toxicity Short Term Long Term
    35. 35. Initial Assessment: PATHS      Assess for Psychological status Assess for Adherence barriers Assess for Treatment readiness Assess for Health Literacy Assess for Support system
    36. 36. Therapy is forever  Adherence must be over 90%  Retention in care is critical for long term success.  Principles of Highly Active Antiretroviral Therapy (HAART)
    37. 37. Targets of HIV Therapy Integrase Inhibitors Entry Inhibitors: Fusion, CD4, CCR5 CXCR4 Nucleus RNA Protease HIV Reverse transcriptase DNA CD4+ T-Cell Reverse transcriptase inhibitors: NRTI (nucleosides, nucleotides) NNRTI Protease inhibitors
    38. 38. Classes of ART Nucleoside Reverse Transcriptase Inhibitors Non-nucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Fusion Inhibitors Integrase inhibitors HAART: Highly Active Antiretroviral Therapy
    39. 39. Current ARV Medications NRTI PI  Abacavir (ABC)  Didanosine (ddI)  Emtricitabine (FTC)  Lamivudine (3TC)  Stavudine (d4T)  Tenofovir (TDF)  Zidovudine (AZT, ZDV)  Atazanavir (ATV)  Darunavir (DRV)  Fosamprenavir (FPV)  Indinavir (IDV)  Lopinavir (LPV)  Nelfinavir (NFV)  Ritonavir (RTV)  Saquinavir (SQV)  Tipranavir (TPV) NNRTI  Delavirdine (DLV)  Efavirenz (EFV)  Etravirine (ETR)  Nevirapine (NVP)  Rilpivirine (RPV) February 2013 Integrase Inhibitor (II)  Raltegravir (RAL)  Elvitegravir* (EVG) Dolutegravir Fusion Inhibitor  Enfuvirtide (ENF, T-20) CCR5 Antagonist  Maraviroc (MVC) www.aidsetc.org 40
    40. 40. Initial Regimens: Preferred NNRTI based EFV/TDF/FTC1,2 PI based ATV/r + TDF/FTC² DRV/r (QD) + TDF/FTC² II based RAL + TDF/FTC² Pregnant women LPV/r (BID) + ZDV/3TC² 1. EFV should not be used during the first trimester of pregnancy or in women trying to conceive or not using effective and consistent contraception. 2. 3TC can be used in place of FTC and vice versa. TDF should be used with caution in patients with renal insufficiency. March 2012 www.aidsetc.org 41
    41. 41. NNRTI Integrase Protease The visual preferred therapies
    42. 42. Viral Load Testing    Viral Load and Progression of Disease Type of test ordered: real time PCR Lower limit of detection is 20 copies Generally don’t measure this or CD4 in acute hospital setting or with intercurrent illness or within 2 weeks of vaccination
    43. 43. Actually < 20 copies Goal of Therapy
    44. 44. Treatment-Experienced Patients: ART Failure  Virologic failure: ◦ HIV RNA >400 copies/mL after 24 weeks, >50 copies/mL after 48 weeks, or >400 copies/mL after viral suppression  Immunologic failure: ◦ Failure to achieve and maintain adequate CD4 increase despite virologic suppression  Clinical progression: ◦ Occurrence of HIV-related events (after ≥3 months on therapy; excludes immune reconstitution syndromes) October 2011 www.aidsetc.org 45
    45. 45. Mortality and HAART Use Over Time -- All HOPS Patients Updated as of 2Q2013 16 100 90 80 12 70 10 8 D eath P er 10 0 P ers on Y ea rs % P atie nts o n H A AR T 60 50 40 6 30 4 20 2 10 0 0 Quarter End of observation defined as the earlier of status change date and last contact + 365 days . 8/14/13 Cerner Corporation The Success Story % of Patients on HAART Deaths per 100 Person Years 14
    46. 46. HIV treatment cascade
    47. 47. Predictors of Inadequate Adherence          Regimen complexity and pill burden Low literacy level Active drug use or alcoholism Stigma Mental illness (especially depression) Cognitive impairment Lack of patient education Medication adverse effects Treatment fatigue November 2008 AETC National Resource Center, www.aidsetc.org
    48. 48.     Emotional and practical supports Convenience of regimen Understanding of the importance of adherence Belief in efficacy of medications •Feeling comfortable taking medications in front of others •Keeping clinic appointments •Severity of symptoms or illness Predictors of Good Adherence November 2008 AETC National Resource Center, www.aidsetc.org
    49. 49. Prevention of Opportunistic Infections CD4 < 200 cells/mm3  Pneumocystis juroveci  Toxoplasmosis  CD4 < 50 cells/mm3  Mycobacterium avium 
    50. 50.   Women: over age 45 with risks for CV disease (USPSTF) AGES 14-24 Women with HIV qualify ◦ Low HDL ◦ High LDL ◦ High hsCRP Health Maintenance Screening: Lipids Mulligan, Clin Inf Dis 2010
    51. 51.  New onset or worsening of symptoms of an infection or inflammatory condition after initiation of antiretroviral therapy  Symptoms not explained by a newly acquired infection, the predicted course of a previously diagnosed infection or adverse effects of drug therapy A decrease in HIV RNA by at least 1 log10  Risk higher with lower CD4 count at initiation of HAART  Immune Reconstitution Inflammatory Syndrome (IRIS)
    52. 52. Case Definition: • A paradoxical deterioration in clinical status after initiating highly active antiretroviral therapy (HAART) attributable to the recovery of the immune response to latent or subclinical infectious or non-infectious processes Other Nomenclature • Immune reconstitution inflammatory syndrome (IRIS) • Immune restoration/restitution/recovery disease • Immune rebound illness • HAART attacks Immune Reconstitution
    53. 53. Antiretroviral Therapy Improves Qualitative and Quantitative Immune Defects Immune suppression/deficiency HIV replication Immune activation Qualitative/functio nal immune defects Quantitative immune defects Response to recall antigens CD4 counts Impaired pathogen -specific immunity OI Immune Reconstitution HAART HIV replication Immune activation Qualitative/function al immune defects Quantitative immune defects Reversal of anergy Redistribution, death (HIV-, activation-induced), production (peripheral expansion and thymic) Lymphocyte proliferative capacity Improved pathogenspecific immunity Improved immune control 54 Migueles, Buenos Aires 2003
    54. 54. Clinical factors Associated with IRIS Male Sex Lower CD4 cell count/ percentage at ART initiation  Higher HIV RNA at ART initiation  Lower CD4:CD8 ration at ART initiation  More rapid initial fall in HIV RNA on ART  Antiretroviral naïve at time of OI diagnosis  Shorter interval between OI therapy initiation and ART initiation    †Derived from cohorts where IRIS due to multiple pathogens were reported (i.e. cohorts which examined only TB-IRIS were excluded
    55. 55. HIV Disease Contributes to NonAIDS Events Low CD4+ T-cell nadir Coinfections (hepatitis, CMV, EBV, and HPV) Persistent inflammation Increased comorbidities Cumulative cART exposure Lifestyle (smoking, etc) Aging Adapted from Deeks SG, et al. BMJ. 2009;338:a3172. Operskalski EA. Curr HIV/AIDS Rep. 2011;8:12-22.
    56. 56.          Lactic acidosis/hepatic steatosis Hepatotoxicity Insulin resistance, diabetes mellitus Fat maldistribution Hyperlipidemia Cardiovascular and cerebrovascular effects Increased bleeding in hemophiliacs Osteonecrosis, osteopenia, osteoporosis Rash ART-Associated Adverse Effects December 2009 www.aidsetc.org 57
    57. 57. HIV and Bone Disease Continuous ART associated with greater bone loss1  Certain ART with higher risk e.g. tenofovir  Vitamin D deficiency  Increased fractures2  1Grund B, et al. ICAAC/IDSA 2008. Abstract 2312a 2Young, CID, 2011
    58. 58. Traditional Factors Are the Biggest Contributor to CHD in HIV Population Family history Inactivity, diet Abdominal obesity* Sex Age Cigarette smoking CHD risk Lipids* Hypertension* HIV infection† Hyperglycemia HAART† Emerging factors: Lp(a), CRP, IMT, and endothelial function *Component of metabolic syndrome. †Precise contribution unclear. Insulin resistance* Diabetes
    59. 59.  High levels of DDimer, CRP, IL-6 Smoking rates  Etc…..  Immune activation
    60. 60. HIV and Hepatitis C      Challenges of therapy in co infection Accelerated course of HCV when have HIV Increased risk of hepatotoxicity with ART Impact on mortality/morbidity Interactions with ART and new HCV RX (DAA)
    61. 61.  Epidemiology-local  Screening and Diagnosis  Evaluation of the HIV+ patient  Treatment updates  Ophthalmology connections Objectives for today
    62. 62. Retrospective studies: CMV associated IRIS was common 18%  Prospective studies: 63% in those with prior CMV disease  Immune recovery vitritis  Immune recovery uveitis   Secondary to residual CMV antigens or proteins CMV and IRIS
    63. 63. Other ocular OI  Syphilitic  H zoster  Molluscum  Toxo  Infectious  HSV  Pneumocystis  Cryptococcal CMV  Related to low CD4 < 50  Genetics related to IL-10 signaling may be related to risk Ocular OI :CMV retinitis and others
    64. 64. Guidelines:  -for CD4< 50 and + CMV PCR with retinal lesions consider valganciclovir with initiation of HAART  Continue x 3-6 months during period of risk CMV Retinitis and Immune Recovery
    65. 65. Four Prevention OpportunitiesCohen et al, JCI, 2008 Cohen IAS 2008 UNEXPOSED EXPOSED EXPOSED INFECTED (precoital/coital) (postcoital) Behavioral, Structural Structural Circumcision Condoms STDs YEARS Vaccines ART PrEP Microbicides HOURS Vaccines ART PEP 72h Treatment Of HIV Reduced Infectivity YEARS
    66. 66.   PREP studies Using antivirals to prevent HIV in uninfected Pre-exposure Prophylaxis
    67. 67. HPTN 052 1763 discordant heterosexual couples 9 countries, 13 sites Randomization Immediate ART 350-550cells/uL AZT+3TC+EFV Deferred ART CD4 <250 Endpoints: i) HIV Transmission to partners ii) OIs and clinical Events iii) ART toxicity
    68. 68. HPTN 052: use of ART in serodiscordant couples  Heterosexual couples : treat HIV+ partner above 350 cells compared delay ART until <350 Reduction in HIV infection in those treated immediately
    69. 69.      Focus on testing, linkage and retention New models for prevention Treatment: more once a day regimens Managing immune reconstitution Non-HIV complications predominate HIV 2012

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