7/27/2019 Hiv Co-morbidities - Treatment Challenge
1/40
Treatment challenge
7/27/2019 Hiv Co-morbidities - Treatment Challenge
2/40
Highly active ART (HAART) reduce AIDS-related mortality and morbidity.
Has transformed HIV/AIDS from a life-threatening disease to chronic illness.
Improved life expectancy of PLWHA.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
3/40
Projected mean age at death for patient diagnosedat the age of 30 with CD4 of 400cell/ml in well-resourced setting is 75 years old.
Only 7 years less than non-HIV population.
Comparable with effect of cigarette smoking.
- Nakagawa F et al. AIDS 2011
In low-income country, 28 additional years among
patients diagnosed at age 35. Still as high as non-HIV population in that country.
- Mille EJ et al. Ann Intern Med 2011;155:209-16
7/27/2019 Hiv Co-morbidities - Treatment Challenge
4/40
Aging of the HIV-positive population is anunexpected development in the history ofHIV/AIDS.
From opportunistic infections and AIDS-related malignancies to occurrence of disease inpeople with mild or moderate immunedeficiency.
- Non-AIDS morbidity and mortality. The focus of HIV medicine is shifting
successful treatment beyond CD4 and/or
viral load.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
5/40
Non-infectious co-morbidities that arecommon among agingpersons in the general
population have emergedas important cause ofdeath.
Non-AIDS related
malignancies,cardiovascular disease,and liver toxicity
1999-2000
(N = 255)
2009-2011
(N = 548)
Weber R, et al. AIDS 2012. Abstract THAB0304.
34%
16%10%
8%
32%
AIDS related Liver relatedCVD related NADMOther/unknown
22%
9%
10%20%
39%
AIDS related Liver-relatedCVD related NADMOther/unknown
7/27/2019 Hiv Co-morbidities - Treatment Challenge
6/40
Stigma
HAART side
effects
Opportunistic
infections
STDs
Psychological
issues
Viral
hepatitis
7/27/2019 Hiv Co-morbidities - Treatment Challenge
7/40
Non-AIDS defining malignancies (NADM).
Cardiovascular diseases.
Chronic hepatitis co-infections B and C.
HIV- associated neurological disease (HAND).
HIV-associated-Non-AIDS (HANA) conditions
7/27/2019 Hiv Co-morbidities - Treatment Challenge
8/40
HAART associated with a reduced incidence ofthe two major AIDS-associated malignancies Kaposis sarcoma and high-grade non-Hodgkin
lymphoma. Twice the risk of developing a non-AIDS
defining cancer than the general population
Immunodeficiency (i.e. low CD4 cell count)may not to be the sole crucial factor.
- Lifestyle habits, co-infection with oncogenicviruses and longevity
Higher in men and advanced stage of AIDS
7/27/2019 Hiv Co-morbidities - Treatment Challenge
9/40
Hodgkin lymphoma
Lung cancer
Hepatocelluar carcinoma
Vulvar and vaginal intraepithelial neoplasia
Anal cancer
7/27/2019 Hiv Co-morbidities - Treatment Challenge
10/40
Unexpected increase in HIV-associated Hodgkinsdisease
Aggressive disease clinically and histologically.
Poorer outcome.
80-100% are EBV-positive.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
11/40
Pre-HAART - median survival of 12 years,despite chemotherapy.
BEACOPP regime + HAART - complete
response rate of 100%, overall survival of 83%at 2 years
ABVD regime + HAART - overall survival of76% at 5 years
7/27/2019 Hiv Co-morbidities - Treatment Challenge
12/40
Increased several fold compared with age-matched and gender-matched populations.
Usually diagnosed with locally advanced or
metastatic disease.- Similar outcome compared to non-HIV
population.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
13/40
Increased risk in HIV patients, occurred atyounger age.
Underlying chronic Hepatitis B and C.
Alcoholism
Similar outcome in non-HIV population
7/27/2019 Hiv Co-morbidities - Treatment Challenge
14/40
Individuals who practice receptive analintercourse.
Increasing number of cases being reported.
HAART does not decrease the incidence. Chemoresponsive - equivalent to non-HIV
patients.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
15/40
Rates are significantly lower than in the non-HIV.
HAART or their HIV status did not influence
- PSA levels- clinical presentation
- tumor grade, stage
Management and treatment outcome similar toHIV-negative counterpart
7/27/2019 Hiv Co-morbidities - Treatment Challenge
16/40
Treatment with antiretrovirals did not appearto have an impact on cancer rates.
Generally, higher CD4 counts is associated
with lower risk of NADM. Studies have shown that most patients with
NADC and well controlled HIV viremia can bemanaged similarly; and with comparableoutcome to their HIV-negative counterparts.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
17/40
HIV infection is pro-artherogenic;
- increased systemic inflammation
- hypercoagulation
- decreased vascular reactivity.
Changes in lipid profile;
- decreases in serum total serum cholesterol and HDL
- increases in serum triglycerides and LDL
Direct consequences of both chronic viremia and of
persistent immune activation:
7/27/2019 Hiv Co-morbidities - Treatment Challenge
18/40
7/27/2019 Hiv Co-morbidities - Treatment Challenge
19/40
Anti Retroviral Agent Potential adverse CVS effect
Protease inhibitor (PI) Central obesity
TC,
LDL-C,
TG;Insulin resistance
NRTIs stavudine
- abacavir
TGInsulin resistancecellular oxidative metabolism
systemic inflammatory biomarkerplatelet activation
NNRTIs - efavirenz TC, LDL-C
7/27/2019 Hiv Co-morbidities - Treatment Challenge
20/40
Triant et al. J Clin Endocrinol Metab. 2007; 92(7): 25062512
7/27/2019 Hiv Co-morbidities - Treatment Challenge
21/40
HIV patients are at higher risk of developingCVD complication.
Routine CVD screening and prevention
measures should be part of routine care for allHIV-infected persons.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
22/40
7/27/2019 Hiv Co-morbidities - Treatment Challenge
23/40
Independently associated with an increasedrisk of progression to AIDS or death, despite asimilar use of antiretroviral therapies
Patients with dual infection may be less likelyto achieve a CD4 count rise of at least 50cells/mL within 1 year of starting HAART
HIV viral load response to therapy was similar
7/27/2019 Hiv Co-morbidities - Treatment Challenge
24/40
Progression is likely to occur more frequentlyand at a faster rate
(2030% of immunocompetent individuals with
HCV will progress to cirrhosis over an average of1530 years)
Coinfected patients have comparably higherlevels of HCV viraemia are inverselycorrelated with the CD4 cell count
Spontaneous clearance occur in < 15% ofpatients
7/27/2019 Hiv Co-morbidities - Treatment Challenge
25/40
Use of HAART:
i. Associated with better hepatic outcomes in
HIV/HCV-coinfected patients
ii. Slower fibrosis progression rate than those
with detectable HIV RNA
The risk of severe hepatotoxicity with HAART
is increased for HIV/HCV-coinfected patientswith advanced (METAVIR stage 3 or 4) fibrosis
7/27/2019 Hiv Co-morbidities - Treatment Challenge
26/40
HCV therapy should be offered to all eligiblepatients regardless of CD4 counts
Initiating HCV therapy early is potentially
advantageous for the subsequent managementof the patient with HIV infection
HCV can be eradicatedin almost half ofpatients who undergo combination HCVtherapy.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
27/40
Data suggest that HAART favorably affects thecourse of HCV in HIV-infected patients.
HAART decreases the rate of death due to liver
disease. HAART should not be withheld from
HIV/HCV-coinfected persons dues to fears oftoxicity.
Overall reluctance by patients and providers toinitiate HCV therapy have made managementof chronic HCV infection a major challenge in
the HIV-infected population.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
28/40
7/27/2019 Hiv Co-morbidities - Treatment Challenge
29/40
The natural history of HIV infection does notseem to be influenced by hepatitis B
Increased rate of antiretroviral-related
hepatotoxicity Increased risk of immune-reconstitution
hepatitis
7/27/2019 Hiv Co-morbidities - Treatment Challenge
30/40
Liver damage in HBV infection isimmunopathic, so liver disease would beexpected to be less severe in HIV infectedperson.
Conflicting evidence
At very high levels of viral replication, HBVmay have a direct cytopathic effect increased
rate of progression to cirrhosis. Progression to liver cancer is more rapid
7/27/2019 Hiv Co-morbidities - Treatment Challenge
31/40
There are currently seven drugs that have beenapproved for use against HBV:
Four have additional HIV activity:
- lamivudine (3TC)- emtricitabine (FTC)
- tenofovir (TDF)
- entecavir Three are only active against HBV:
- interferon, adefovir and telbivudine
7/27/2019 Hiv Co-morbidities - Treatment Challenge
32/40
Therapy with 3TC, or FTC, without a secondanti-HBV-active drug is not recommended
Combining 3TC/FTC with tenofovir may
reduce the risk of breakthrough resistance
CD4 < 350cells/ml start ART
CD4 350-500cells/ml combined ART/HBVregime
Earlier initiation of ART (CD4> 500cells/ml)should still be considered
7/27/2019 Hiv Co-morbidities - Treatment Challenge
33/40
BHIVA Guidelines. HIV Medicine (2010), 11, 1
30
7/27/2019 Hiv Co-morbidities - Treatment Challenge
34/40
HIV can infect the brain and impair centralnervous system (CNS) function.
HIV-associated neurocognitive disorders(HAND) remain common despite HAART.
Its prevalence is actually increasing, due in partto the longer life expectancy for individualswith HIV.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
35/40
Nearly 50% of HIV patients demonstrateneuropsychological testing performance that isbelow expectations.
- half are symptomatic and few meet researchclassification of dementia.
Quality of life is greatly affected- disruptions in ability to perform activities of
daily living.
- adherence to the HAART regime.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
36/40
Cold Spring Harb Perspect Med. 2012;2(6): a007120
7/27/2019 Hiv Co-morbidities - Treatment Challenge
37/40
7/27/2019 Hiv Co-morbidities - Treatment Challenge
38/40
Combination antiretroviral therapy has had adramatic beneficial impact on the incidenceand prevalence of severe forms of HAND
Milder form of HAND seems to persist despiteHAART
Adjuvant therapy being studied: minocycline,selegiline.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
39/40
HAND incidence correlates with the degree ofimmune suppression as well as the duration ofHIV infection.
There has not been any successful adjuvanttherapy: to treat the CNS specifically ratherthan the virus.
HAART is still the essential primary approachto treat HAND.
7/27/2019 Hiv Co-morbidities - Treatment Challenge
40/40
As HIV-infected patients live longer, they areexposed to various co-morbidities which mayor may not be directly related to underlyingchronic HIV infection.
As most of these conditions related to thedegree of immune suppression, early initiationof HAART may reduce the risk of developingthese co-morbidities i.e CD4 < 500.
There appears to be a need for bettertreatments particularly for neurologicalproblems, non-AIDS defining cancers and
di l li i