adults and children newly infected with hiv in 2008

Adults and Children Newly Infected With HIV in 2008

UNAIDS, 2008. http://www.unaids.org.

North Africa and Middle East

40,000Total: 380,000

Sub-Saharan Africa1.9 million

Total: 22 million

Eastern Europe and Central Asia110,000

Total: 1.5 million

Oceania13,000

Total: 74,000

Caribbean20,000

Total: 230,000

Asia380,000

Total: 4.2 million

Latin America140,000

Total: 1.7 million

North America and Western/Central Europe

81,000Total: 2.0 million

3

Human Immunodeficiency Viruses• HIV-2

– HIV-2 is less virulent and less transmissible

– HIV-2 is closely related to SIVsm, found in Sooty Mangebey monkeys

– HIV-2 is epidemic in Western Africa, India

• HIV-1

– HIV-1 is more virulent and more transmissible

– HIV-1 is closely related to SIVcpz, found in Chimpanzees

– HIV-1 is pandemic

– HIV-1 strains are divided into three groups (M - main, N, O - outlier)

– HIV-1 group M is divided into several subtypes (Clades A through J)

4

Global HIV Estimates• Cumulative HIV-1 infections = 80 million• Persons living with HIV-1

– Adults 40 million– Children 2.7 million

• New HIV-1 infections yearly– Adults 5 million– Children 0.9 million

• AIDS Orphans– 14 million– 20 million by 2010

5

Global Burden of HIV-1 Infection in Women

• Half of all new infections occur in women • Half of the 40 million individuals living with HIV are

women– Sub-Saharan Africa: 60% (75% ages 15-24)– Caribbean: 50%– Latin America: 35%– South/SE Asia: 30%

Quinn and Overbaugh, Science 308: 1582, 2005

6

Where do we find HIV?• Blood

• Seminal fluid

• Vaginal fluid

• Breast milk

• Saliva

• Tears

• Urine/feces

7

How is it transmitted (cont)• Use of unclean needles for

drug use including steroids,

piercing

• From HIV+ mother to unborn child

• Contaminated blood products

• Needlesticks

8

Who is at risk for HIV?

• Men who have unprotected sex with men

• Men who have unprotected sex with men and women

• Men/women who use unclean needles

• Women who have unprotected sex with women who are menstruating

• Women who have unprotected sex with men

9

What age groups are vulnerable?• Women have represented approximately 50% of cases of HIV in Africa all along

• In the US, women were only 5% in the 1980’s now approaching 50%

• Fastest growing numbers of new cases in ages 13-24 and over 50

• Men who have sex with men have begun to represent an upward spiral of new cases

11CD4 ( T Helper) CellHuman DNA chromosome

Cellular CD4 receptor

12


HIV RNA chromosome

IntegraseReverse transcriptase

Protease

CD4 ( T Helper) CellHuman DNA chromosome

HIV

gp41gp120

13

1. HIV approaches CD4 cell

4. Fusion of cell and virus

3. Conformational change in gp120, exposing

hydrophobic fusion protein (harpoon) of gp41

2. Gp120-CD4 interaction

14

Reverse transcriptaseIntegrase

Proteasegp120gp41

HIV RNA chromosome



15


Proteasegp120gp41

HIV RNA chromosome



RNA nucleotides

16


Proteasegp120gp41

HIV RNA chromosome



RNA nucleotidesDNA nucleotides

17


Proteasegp120gp41

HIV RNA chromosome


HIV DNA provirusCD4 ( T Helper) CellHuman DNA chromosome

18


Proteasegp120gp41

HIV RNA chromosome



Reverse Transcriptase Inhibitors:Nucleoside and Non-Nucleosides

19


Proteasegp120gp41

HIV RNA chromosome



20


Proteasegp120gp41

HIV RNA chromosome



21

HIV Protease

Non-functionalgp160 precursor gp41

gp120

Functional proteins

Protease Inhibitors

22


Proteasegp120gp41

HIV RNA chromosome



HIV

23

CD4 Cell Count and Viral Load• CD4 cell count

– The number of T helper cells, or CD4 cells, in your blood. The count is measured as the number of cells per cubic millimeter (cells/mm3).

Higher CD4 cells counts are a sign of a healthier immune system.

Levels below 1000 indicate that the immune system is impaired.

Blood tests measuring CD4 cells can help to determine if HAART is working.

• Viral Load– The number of viruses circulating in your blood. Measured as

counts per milliliter (c/mL or counts/mL). 1 milliliter = a cubic

centimeter. Counts of 50 and below are termed “undetectable”.

Blood Test: Viral Load also used to indicate whether HAART is

Working/resistance is developing

24

Number of AIDS cases and number of deaths from AIDS in the USA 1981-2001

10th CROI, Boston 2003, #4; Incidence and deaths data from the CDC

010,00020,00030,00040,00050,00060,00070,00080,00090,000

81 85 9590 00 01

Year

0

100,000

200,000

300,000

400,000

Num

ber o

f new

AID

S ca

ses/

year

Total number of A

IDS casesN

umbe

r of d

eath

sfro

m

AID

S/ye

ar

26

When to Start Therapy?

Infection with HIV

0.5–15 (?)years

2–3years

6–24weeks

HIV RNA load CD4lymphocytes

Clinical AIDS

1996 2004 1987

Original slide courtesy of Dr Sven A. Danner.

Treatmentinitiation in:

2727

Updated IAS-USA Guidelines: When to Start

Year Recommendation to Begin

Immediate Therapy

Recommendation to Consider Immediate Therapy

Recommendation to Delay Therapy

2006 Active AIDS No history of active

AIDS, but CD4+ cell count ≤ 200 cells/mm3

No history of active AIDS, but CD4+ cell count from 200-350 cells/mm3

CD4+ cell count > 350 cells/mm3

but rapid CD4+ cell count decline, HIV-1 RNA > 100,000 copies/mL, high CV risk patients, other non-AIDS risk factors*


2008 Active AIDS No history of active

AIDS, but CD4+ cell count ≤ 350 cells/mm3


but rapid CD4+ cell count decline, HIV-1 RNA > 100,000 copies/mL, high CV risk patients, other non-AIDS risk factors*


Hammer SM, et al. JAMA. 2008;300:555-570.*Non-AIDS risk factors include HIV-associated nephropathy, hepatitis C, hepatitis B

28

Start on the most potent drug to keep the virus down

Adapted from Bangsberg DR, et al. XI International HIV Drug Resistance Workshop. Seville, 2002. #160

To avoid resistance:To avoid resistance:• Pr0viders should use a potent medication that will achieve maximum Pr0viders should use a potent medication that will achieve maximum

suppression of the virus and that the patient can strictly stick tosuppression of the virus and that the patient can strictly stick to• The patient should adhere to the regimenThe patient should adhere to the regimen

• 100% adherence to a partially effective regimen will still result in virologic failure due to resistance

• With a highly effective regimen, resistance is highest when adherence is intermediate

A partiallyA partiallyeffectiveeffectiveregimenregimen

A highlyA highlyeffectiveeffectiveregimenregimen

Low High Adherence

High

Res

ista

nce

Low

29

Overview of Available Antiretroviral Sites of Action

30

News on metabolic side effects

43rd ICAAC, Chicago 2003, #H-1947, #H-1948, #H-1956, #H-1958

News in brief

Abnormal fat distribution• A diet rich in polyunsaturated fats may help to reduce cell death which has been

correlated with abnormal fat distribution as a side effect of HIV meds – the implications are unknown as this study was done in the laboratory and not in patients

Avascular necrosis• Smoking is a risk factor for avascular necrosis in HIV-infected patients

Cardiovascular• Smoking was the most frequent indicator of CV risk for patients on HAART.

Other considerations included : lower CD4 nadir, male gender, protease inhibitor use.

Triglycerides• In 23 patients (of ~1300 patients) who had received HAART from 1997-2003

and who had developed high trigs:– Severe high trigs were more likely in patients receiving high dose ritonavir (more than 300 mg

per day)– High trigs above 1000 mg/dL is associated with pancreatitis– There were no cases of pancreatitis associated with high trigs in this study

32

Risk Factors: Lipodystrophy

– Age > 40 years

– Hx of AIDS > 3 years

– CD4+ nadir < 100 or CD4+% nadir < 15%

– Body mass index (BMI) loss of ≥ 1 kg/m2

– BMI change of ≥ 2 kg/m2

– White race

– Duration of Rx with indinavir or stavudine associated with increased risk of lipodystrophy

Lichtenstein KA, et al. J Acquir Immune Defic Syndr. 2003;32:48-56.

33

time (days) from start of dual therapyto lipoatrophy

Lipoatrophy Risk: Lipoatrophy Risk: Dual NRTI + PI vs Dual NRTIDual NRTI + PI vs Dual NRTI

Risk of lipoatrophy with 2 NRTI + PI greater than with 2 NRTI alone

prob

abili

ty o

f rem

aini

ng fr

ee

of s

ubcu

tane

ous

lipoa

troph

y

0.0

0.2

0.4

0.6

0.8

1.0

0 200 400 600 800 1000

2 NRTIs

2 NRTIs + PI

Mallal SA. AIDS 2000;14:1309

34

Evolution of body fat over time,Evolution of body fat over time,following initiation of ARTfollowing initiation of ART

+30

+15

0

-15

-30

0 24 48 72 96 120 144Week

Med

ian

% c

hang

e fr

om B

L

• Australian lipodystrophy cohort starting HAART

• measurements by DEXA:– initial increase in

central and peripheral fat

– limb fat declines from baseline after ~1 yr

– central abdominal fat remains increased from baseline

Mallon PWG, et al. AIDS 2002;

central abdominal fatlimb fatlean mass

35

1

4

1

12

3

19

02468

101214161820

GS 903 Study:GS 903 Study:Patients (%) with LipodystrophyPatients (%) with Lipodystrophy++

% P

atie

nts

with

Sel

ecte

d To

xici

ties TDF+3TC+EFV

d4T+3TC+EFV

Week 48 Week 96 Week 144

+ Investigator-defined* p value < 0.001

*

*

*

*

36

Metabolic Syndrome• Many different definitions of the metabolic syndrome

– Prevalence and association with HIV infection may be dependent on choice of definition

• WIHS: found higher prevalence of metabolic syndrome in HIV-infected women, but factors significantly associated with metabolic syndrome were traditional risk factors (age, race, higher BMI, smoking), not HIV related[1]

• MACS: HIV-infected men who are treated have larger waists as they age; reversal of previous decrease in waist size with NRTI treatment[2]

1. Sobieszczyk ME, et al. IAC 2006. Abstract WEPE0147. 2. Brown T, et al. IAC 2006. Abstract WEPE0136.

37

• Australian Prevalence Study; buffalo hump was found in 2% of HIV+

Buffalo hump (BH) and associated metabolic abnormalities

1. Miller M, HIV Med 2003; 4:293-301; Mallon PWG, et al. 2nd IAS, Paris 2003, #715

• Buffalo hump is commonly found in overweight people and is associated with metabolic changes seen in overweight individuals - insulin resistance and larger body mass index

• Presence of BH is not associated with high blood lipids, e.g. triglycerides, cholesterol

38

Adherence

40

Treatment Plan- Individualized• Pill burden

• Number of doses per day

• Lifestyle issues

• Side effects

• Effectiveness (potency and durability)

• Preserving future options(sequencing)

• Provide adherence support

41

Advances in current treatment and care: Summary

• Once-daily combinations

• No required water or food

• Many can be stored in cool areas but no need for refrigeration

• Side effects less gastrointestinal but more metabolic

42

How Much Adherence is Needed?

0

20

40

60

80

100

% o

f Pat

ient

s w

ith V

iral

Load

<40

0 co

pies

/ml

>95% 90-95% 80-90% 70-80% <70%

Adherence(number of pills taken / number of pills prescribed)

Ann Intern Med 2000;133:21

43

What is treatment failure?• When antiretroviral medications stop controlling HIV,viral load goes up and CD4 counts go down

• Immune damage continues

• Risk of an opportunistic infection increases

• Drug resistance is a major cause of treatment failure.

44

Nurses and HIV• Leaders

• Educators

• Counselors /Testers

• Treatment managers

• Adherence coaches

• Symptom managers

• Prevention counselors

adults and children newly infected with hiv in 2008

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