Hiv Co-morbidities - Treatment Challenge

7/27/2019 Hiv Co-morbidities - Treatment Challenge

1/40

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.


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


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.


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


6/40

Stigma

HAART side

effects

Opportunistic

infections

STDs

Psychological

issues

Viral

hepatitis


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


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


9/40

Hodgkin lymphoma

Lung cancer

Hepatocelluar carcinoma

Vulvar and vaginal intraepithelial neoplasia

Anal cancer


10/40

Unexpected increase in HIV-associated Hodgkinsdisease

Aggressive disease clinically and histologically.

Poorer outcome.

80-100% are EBV-positive.


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


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.


13/40

Increased risk in HIV patients, occurred atyounger age.

Underlying chronic Hepatitis B and C.

Alcoholism

Similar outcome in non-HIV population


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.


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


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.


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:


18/40


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


20/40

Triant et al. J Clin Endocrinol Metab. 2007; 92(7): 25062512


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.


22/40


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


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


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


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.


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.


28/40


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


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


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


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


33/40

BHIVA Guidelines. HIV Medicine (2010), 11, 1

30


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.


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.


36/40

Cold Spring Harb Perspect Med. 2012;2(6): a007120


37/40


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.


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.


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

Documents

Hiv Co-morbidities - Treatment Challenge