Living Longer With HIV:
New Insights and Issues

A Monograph Series with
Accompanying Slides

Long-Term

Complications in

People with HIV

Living Longer with HIV: New
Insights and Issues

The following slides provide an overview
of the scientific material available in the
accompanying full-text pdf file of the
monograph titled, Long-Term
Complications in People with HIV.

All of the information contained in the
monograph and slides is based on the
referenced materials in the monograph
pdf file.

Long-Term Complications in
People with HIV

Long-Term Complications in
People with HIV

•

The Benefits—and Limitations—of cART

–

Persistence of HIV Replication After Suppression

–

Persistent Immune Deficits

•

Association of HIV with Non-AIDS-related Morbidities

–

Frailty

–

Liver Disease

–

Renal Disease

–

Non-AIDS-related Malignancies

–

Cardiovascular Disease

–

Metabolic Alterations

Overview

cART=combination antiretroviral therapy.

The Benefits and

Limitations of cART

Jarrin I et al. Am J Epidemiol. 2008;168:532-40. Copyright © 2008 Oxford University Press. All rights reserved.

cART Has Dramatically
Decreased the Risk of AIDS-
Defining Disease and Death

Cumulative Incidence of AIDS and Death
Following HIV Seroconversion in
Industrialized Countries

Bhaskaran K et al. JAMA. 2008;300:51-9. Copyright © 2008 American Medical Association. All rights

reserved.

Mortality Rates for HIV+ Individuals
in the First 5 Years after Infection
Similar to Rates for HIV- Population

Excess Mortality Rate for HIV-Infected
Individuals vs
General Population Over Time in
Industrialized Countries

Pre-cART-Era Morbidity vs cART-
Era Morbidity

•

Decline in pre-cART-era OIs and HIV-related

morbidities

1

:

–

Mycobacterial disease, Kaposi’s sarcoma,
CMV, pneumocystosis, etc

•

Emerging morbidities related to:

–

Longer lifespan with HIV

2

–

Incomplete immunologic response

3

–

Persistence of low-level HIV replication
leading to chronic immune activation,
inflammation, and T-cell aging

4

1.Hooshyar D et al. AIDS. 2007;21:2093-100. 2.Shen L et al. J Allergy Clin Immunol. 2008;122:22-8.
3.Appay V et al. J Pathol. 2008;214:231-41. 4.Appay V et al. Exp Gerontol. 2007;42:432-7.

Robbins GK et al. Clin Infect Dis. 2009;48:350-61. Copyright © 2009. University of Chicago Press. All rights

reserved.

Baseline CD4+ Cell Count
Correlates with
cART-Related CD4+ Cell
Reconstitution

Median Increases in CD4+
Cell Count
According to Baseline
CD4+ Stratum

Baker JV et al. AIDS. 2008;22:841-8. Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

Impaired Immune Recovery
Increases Risk for Morbidity and
Mortality

Rates (95% CI) of AIDS and Non-AIDS
Events by Latest CD4+ Cell Count

Association of HIV

with Non-AIDS-

Related

Morbidities

Emergence of Non-AIDS-Related
Morbidities in the cART Era
Results from Numerous Factors

Factors influencing emerging morbidities

include:

•

Advancing age

•

Antiretroviral drug

toxicities

•

Lower CD4+ count

•

Injection drug use

•

Detectable viremia

•

Smoking

•

Hepatitis coinfection

•

Obesity

Goulet JL et al. Clin Infect Dis. 2007;45:1593-601.

Emerging Non-AIDS-Related
Morbidities in the
cART Era

•

Frailty syndrome (accelerated aging)

•

Liver disease

•

Renal disease

•

Non-AIDS-related malignancies

•

Cardiovascular disease

•

Metabolic alterations

Goulet JL et al. Clin Infect Dis. 2007;45:1593-601.

Desquilbet L et al. J Gerontol A Biol Sci Med Sci. 2007;62:1279-86. Copyright © 2007 Oxford University Press.

All rights reserved.

Frailty Syndrome Associated
with Increasing Duration of HIV
Infection

Adjusted Prevalence of Frailty
Syndrome According to Age and
Duration of HIV Infection

Weber R et al. Arch Intern Med. 2006;166:1632-41. Copyright © 2006 American Medical Association. All rights

reserved.

Increasing Frequency of Liver
Disease and Death Associated
with HCV Coinfection

Rate (95% CI) of Liver-Related Deaths by Duration of cART

Patel P et al. Ann Intern Med. 2008;148:728-36.

Non-AIDS-Defining Cancers
Among HIV-Infected Individuals
Increasing in cART Era

Cancer

Standardized Rate Ratio (SRR) (95%

Confidence Interval)

1992-1995

1996-1999

2000-2003

Anal

31.4 (16.2-

60.8)

48.2 (32.4-

71.6)

59.4 (44.0-

80.3)

Hodgkin’s
lymphoma

11.7 (7.5-18.2)

16.6 (11.5-

24.0)

17.9 (12.6-

25.5)

Liver

9.3 (4.8-18.0) 10.2 (6.5-16.1) 7.0 (4.6-10.7)

Lung

3.5 (2.5-4.9)

3.8 (2.8-5.0)

3.6 (2.8-4.6)

Melanoma

1.3 (0.6-2.8)

2.2 (1.3-3.9)

3.0 (2.0-4.7)

Oropharyngeal

2.5 (1.4-4.4)

2.5 (1.6-4.1)

3.0 (2.0-4.5)

Colorectal

2.5 (1.6-4.0)

2.0 (1.3-3.1)

2.4 (1.7-3.3)

D:A:D Study Group et al. N Engl J Med. 2007;356:1723-35. Copyright © 2007 Massachusetts Medical Society.

All rights reserved.

Increasing Incidence of
Cardiovascular Disease Related
to a Variety of Factors

Risk (95% CI) of MI According to
cART Exposure

Aging, obesity, adverse drug events, immune activation, and low-
level viremia may increase risk of cardiovascular disease.

LDL: low-density lipoprotein; NNRTI: nonnucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse
transcriptase inhibitor; PI: protease inhibitor.
—: does not cause adverse reaction; (+): possibly causes adverse reaction; +: sometimes causes adverse reaction;
++: frequently causes adverse reaction.
Grinspoon SK et al. Am J Med. 2005;118(Suppl 2):23S-8S.

Adverse Effects of Different
Antiretroviral
Drug Classes

Effect

NRTIs

NNRTIs

PIs

Lactic acidosis

+

—

—

Lipid changes
Elevated
triglycerides

—

(+)

++

Elevated LDL
cholesterol

—

(+)

+

Insulin resistance

(+)

—

++

Fat redistribution
Lipoatrophy

+

—

+

Fat accumulation

—

—

++

D:A:D Study Group et al. Lancet. 2008;371:1417-26. Copyright © 2008, with permission from Elsevier.

Rates of MI, Stratified by Predicted 10-
year Risk of Coronary Heart Disease and
Recent Use of Didanosine or Abacavir

Living Longer with HIV: Future
Directions in Disease
Management

•

Continued development of new

antiretrovirals with long-term safety profiles

•

Research into etiology of emerging long-term

morbidities, such as liver disease,
malignancies, and cardiovascular events

•

Strategies to interrupt immune activation

resulting from persistent, low-level viremia