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“Acquired Immuno Deficiency Syndrome”
(AIDS) or a set of symptoms and infections
resulting from the damage to the human
immune system caused by the Human
Immunodeficiency Virus (HIV). This condition
progressively reduces the effectiveness of the
immune system and leaves individuals
susceptible to opportunistic infections and
tumors.

4
What is HIV?
HIV is “Human Immunodeficiency Virus”,it is
the virus that cause AIDS.
Human means that it affects only humans
and lives only in humans.
The virus does not live in toilets, mosquitoes,
cups, spoons, on bed sheets or towels that
people with HIV might have used.
Immunodeficiency refers to lack(deficiency)
or breakdown of immune system. The
“immune system” is the body’s resistance or
the body’s defense force for fighting off
infections.
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The virus attacks and eventually overcomes the
body’s immune system. The immune system is
usually able to defend the body against
infections.
A virus is a germ.
What is AIDS?
 AIDS means “Acquired Immunodeficiency

Syndrome”
 To acquire means to “get or develop over a

period of time”
 The immune system breaks down gradually over

time.

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It gets deficient or less and less efficient, under
relentless attack by the multiplying number of
virus in the body.
Syndrome refers to the group or collection of
signs and symptoms of indication of diseases in
a person who has AIDS.

HIV is the infectious stage of the


condition, AIDS is the disease phase.

7
8
HIV came from a similar virus found in
chimpanzees - SIV.
HIV probably entered the United States
around 1970.the first recognized case of
AIDS was in the early 1980s.
HIV is a lent virus (slow virus),which in turn
is a part of a larger group of viruses known
as retro virus

9
Males>females
Occurs in all ages and ethnic groups
All areas of the country are affected
In some city inner areas, as many as 50% of males are
HIV positive
AIDS is now the second leading cause of death for all
men aged 25-44 years
(Unintended injuries is #1 and heart disease is #3 for
this age group)

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 HIV enters the bloodstream through:

Open Cuts

Breaks in the skin

Mucous membranes

Direct injection

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exual Contact: Male-to-male
Male-to-female or vice versa
Female-to-female

lood Exposure: Injecting drug use/needle sharing


Occupational exposure
Transfusion of blood products

erinatal: Transmission from mother to baby


reastfeeding

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Occupational Transmission
Health care worker/ hospital
staff
Laboratory workers

Other routes
Organ transplantation
Artificial insemination
Needle-prick

13
14
Common body fluids that are means of
transmission:

 Blood
 Semen
 Vaginal Secretions
 Breast Milk

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Blood
Semen
18,000 Vaginal
11,000
Fluid Amniotic
7,000 Fluid
4,000 Saliva
1

Average number of HIV particles in 1 ml of these body fluids


16
HIV HIV Infected New HIV
T-Cell T-Cell Virus
Virus

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HIV cannot reproduce outside the human body. It is not spread by:
 Air or drinking water from the same pot with an
infected person.
 Insects: including mosquitoes. Studies conducted
by researchers have shown no evidence of HIV
transmission from insects.
 Saliva, tears, or sweat.  There is no documented
case of HIV being transmitted by spitting.
 Casual contact like shaking hands or sharing
dishes.
 Closed-mouth or “social” kissing.
This is the period of time after becoming
infected when an HIV test is negative.

90 percent of cases test positive within


three months of exposure

10 percent of cases test positive within


three to six months of exposure

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The clinical consequence of HIV infection
comprises of a spectrum ranging from an acute
syndrome with primary infection to a prolonged
asymptomatic stage to advanced disease.
Incubation period: 2 to 10 yrs.

20
Follows 3-6 wks following primary
infection

21
Second phase-
Asymptomatic contact
Initial HIV inf. or after illness of inf.
No symptoms
Last 2 to 10 yrs.

22
Third phase-
PGL (Persistent Generalized Lymphadenopathy)
Enlargement of lymph nodes.
outside the inguinal area
more than 2 areas
more that 3 months

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Fourth phage-Overt Manifestation of AIDS
 ARC(AIDS-related complex): fever, loss of weight,
anorexia, diarrhea plus PGL
 Nervous system symptoms: headache,
convulsion, paralysis, progressive
dementia
 Rare opportunistic infection.
 Unusual malignant tumors.
 Pneumonia.

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Initial Stage---------------- --------Intermediate or Latent Stage--------------
--- Illness Stage

Flu-like Symptoms
Or
No Symptoms Symptom-free AIDS Symptoms

----

Infection
Occurs

----

< 25
26
27
Candidiasis Of Mouth

28
Lymphadenopathy

31
Primary CNS Lymphoma

32
34
Risk factors
Anyone of any age, race, sex or sexual orientation can be
infected with HIV, but you're at greatest risk of
HIV/AIDS if you:
Have unprotected sex with multiple partners. Unprotected sex
means having sex without using a new latex or polyurethane
condom every time.
Have unprotected sex with someone who is HIV-positive.
Have another sexually transmitted disease, such as syphilis, herpes,
Chlamydia, gonorrhea or bacterial vaginosis.
Share needles during intravenous drug use.
Received a blood transfusion or blood products before 1985.

35
Newborns or nursing infants whose mothers tested
positive for HIV but did not receive treatment also are at
high risk.
Fastest growing method of HIV transmission:
heterosexual contact.
Heterosexual transmission is easier from men to women
than from women to men
Risk of acquiring for men is greater if contact occurs
during menstruation
Uncircumcised men are more likely to be seropositive
and contract HIV during sex

36
If mother is HIV positive, 100% of
children will test positive at birth
Breast feeding increases transmission rate

37
There's no vaccine to prevent HIV infection and no cure for
AIDS. Prevention includes educating yourself about HIV and
avoiding any behavior that allows HIV-infected fluids —
blood, semen, vaginal secretions and breast milk — into your
body.
HIV-negative Individual prevention:
Educate yourself and others.
Know the HIV status of any sexual partner.
Use a new latex or polyurethane condom every
time you have sex.
Consider male circumcision.
Use a clean needle.
Be cautious about blood products.
Get regular screening tests.

38
HIV positive individual prevention:
Follow safe-sex practices.
Tell your sexual partners you have HIV.
If your partner is pregnant, tell her you have
HIV.
Tell others who need to know.
Don't share needles or syringes.
Don't donate blood or organs.
Don't share razor blades or toothbrushes.
If you're pregnant, get medical care right
away.
39
Traditionally, prevention is
described as being at three levels:

40
Traditionally, prevention is
described as being at three levels:

41
Traditionally, prevention is
described as being at three levels:

42
43
44
45
46
It is now thought that HIV came from a similar virus found in
chimpanzees - SIV.
HIV probably entered the United States around 1970
CDC in 1981 noticed unusual clusters of Kaposi’s sarcoma in gay men
in NY and San Francisco, which led to the disease to be called GRID (Gay
Related Immune Deficiency).
By 1982 the disease was apparent in heterosexuals and was renamed
AIDS (Acquired Immune Deficiency).
1984- Scientists identify HIV (initially called HTLV-III or LAV) as the
cause of AIDS
1987- AZT is the first drug approved for treating AIDS

http://www.avert.org/aids-timeline.htm
The Ryan White Comprehensive AIDS Resources
Emergency (CARE) Act (Ryan White Care Act,
Ryan White, Pub.L. 101-381, 104 Stat. 576,
enacted August 18, 1990) was an Act of the
U.S. Congress named in honor of Ryan White, an
Indiana teenager who contracted AIDS through a
tainted hemophilia treatment in 1984, and was
expelled from school because of the disease.
White became a well-known advocate for
AIDS research and awareness, until his death on
April 8, 1990.[1]

http://www.avert.org/aids-photo-gallery.php?photo_id=431&gallery_id=7
HIV Prevalence Estimate
Prevalence is the number of people living with HIV/AIDS in a
given year.
At the end of 2003, an estimated 1,039,000 to 1,185,000
persons in the United States were living with HIV/AIDS, with 24%-
27% undiagnosed and unaware of their HIV infection.1
HIV Incidence Estimate
Incidence is the number of new HIV infections that occur during a
given year.
In 2008, CDC estimated that approximately 56,300 people were
newly infected with HIV in 2006 (the most recent year that data
are available). Over half (53%) of these new infections occurred in
gay and bisexual men. African American men and women were
also strongly affected and were estimated to have an incidence
rate than was 7 times greater than the incidence rate among
whites.

http://www.cdc.gov/hiv/topics/surveillance/basic.htm#hivest
Eighty percent of Americans with HIV do not
know they are infected.
Philip Emeagwali
One out of every 100 American men is HIV
positive. The rate of infection has reached
epidemic proportions in 40 developing
nations.
Philip Emeagwali
Transmission categories of adults and
Sex of adults and adolescents with HIV/AIDS
adolescents with HIV/AIDS diagnosed during
diagnosed during 2006
2006

http://www.cdc.gov/hiv/resources/factsheets/us.htm
http://www.cdc.gov/nchhstp/stateprofiles/Louisiana/Louisiana_Profile.htm
Males>females
Occurs in all ages and ethnic groups
All areas of the country are affected
About 2 million adults & 500,000 children in US are HIV
positive (male 1:100; female 1:800)
In some city inner areas, as many as 50% of males are
HIV positive
AIDS is now the second leading cause of death for all
men aged 25-44 years
Unintended injuries is #1 and heart disease is #3 for this
age group
Anyone of any age, race, sex or sexual orientation can be
infected with HIV, but you're at greatest risk of HIV/AIDS if you:
Have unprotected sex with multiple partners. You're at risk
whether you're heterosexual, homosexual or bisexual.
Unprotected sex means having sex without using a new latex or
polyurethane condom every time.
Have unprotected sex with someone who is HIV-positive.
Have another sexually transmitted disease, such as syphilis,
herpes, chlamydia, gonorrhea or bacterial vaginosis.
Share needles during intravenous drug use.
Received a blood transfusion or blood products before 1985.
Have fewer copies of a gene called CCL3L1 that helps fight HIV
infection.
Newborns or nursing infants whose mothers tested positive for
HIV but did not receive treatment also are at high risk.
Most dangerous sexual practice: anal intercourse
Recent evidence that HIV can be transmitted by oral sex
If the patient has AIDS today, most likely homo/bisexual
man
If recently became HIV positive, most likely IV drug
abuser
Fastest growing method of HIV transmission:
heterosexual contact (esp. for blacks and hispanics)
Heterosexual transmission is easier from men to women
than from women to men
Risk of acquiring for men is greater if contact occurs
during menstruation
Uncircumcised men are more likely to be seropositive
and contract HIV during sex
HIV transmission rates:
Risk from single sexual encounter with man who is not a member of
a risk group: 1 in 5 million
Risk from single encounter with man who is a member of a high risk
group: 1 in 20 to 1 in 2
Needle-stick (with HIV-positive blood): 1 in 100 to 1 in 1000
(average 1 in 250)\
Seroconversion from blood transfusion: 2 of 3
If mother is HIV positive, 100% of children will test
positive at birth
About 20% of these will remain HIV positive after 1 year
Breast feeding increases transmission rate
AZT (zidovudine/Azidothymidine) reduces risk by half (to
about 10%). AZT + c-section reduces transmission rate to 5%
Neverapine: If given during labor to mother and to child after
birth, cuts rate to 10%
There's no vaccine to prevent HIV infection and no cure for
AIDS. But it's possible to protect yourself and others from
infection. That means educating yourself about HIV and avoiding
any behavior that allows HIV-infected fluids — blood, semen,
vaginal secretions and breast milk — into your body.
If you're HIV-negative
Educate yourself and others.
Know the HIV status of any sexual partner.
Use a new latex or polyurethane condom every time you have
sex.
Consider male circumcision.
Use a clean needle.
Be cautious about blood products in certain countries.
Get regular screening tests.
Don't become complacent.

http://www.mayoclinic.com/health/hiv-aids/DS00005/DSECTION=prevention
If you're HIV-positive
Follow safe-sex practices.
Tell your sexual partners you have HIV.
If your partner is pregnant, tell her you have HIV.
Tell others who need to know.
Don't share needles or syringes.
Don't donate blood or organs.
Don't share razor blades or toothbrushes.
If you're pregnant, get medical care right away.

http://www.mayoclinic.com/health/hiv-aids/DS00005/DSECTION=prevention
Causative agent: Human Immuno-deficiency Virus
 Enveloped RNA retrovirus
 Spherical 120 nm in diameter envelope proteins make the spikes
on the
 membrane.
 Enveloped truncated conical capsid
 Electron dense core
 Two copies of the single stranded (+) RNA
 Has enzymes: Reverse transcriptase, Integrase & Protease
 Has gag, pol and env structural genes
 Has LTR (long terminal repeats) rev and neg regulatory genes
 HIV infects CD-4 positive cells
◦ CD4+ T-cell lymphocytes
◦ Macrophages
◦ Lymph node follicular dendritic cells
◦ Langerhans cells
 Binding to CD4 by gp120
 Entry into cell by fusion requires gp41 and

coreceptors
◦ CCR5 (Beta chemokine receptor)
◦ CXCR4 (alpha chemokine receptor)
 Envelope lost and RNA uncoated
 DNA made from RNA using reverse transcriptase
 DNA and Integrase migrate to nucleus forming a

provirus by integrating viral DNA to host DNA


 Rate of viral replication regulated by the activity of
regulatory proteins (tat/rev, nef, etc)
 Co-infections (e.g., mycobacterial) stimulate the HIV-
infected cells to produce more virus
 Transcription and translation produces necessary
polyprotiens which are cleaved by the HIV protease
 Assembly
 Maturation/release of virus
 Category A (A1-A3: > 500 to <200 CD4+ T cells/µl): Acute and
asymptomatic HIV infection +persistent generalized
lymphadenopathy
 Category B (B1-B3: 500 to <200 CD4+ T cells/µl) : symptomatic but
not conditions in C
 Category C (C1-C3: 500 to <200 CD4+ T cells/µl) : AIDS defining
conditions
 AIDS: A3, B3, or C1-3
 Acute phase has high level of viral production and mononucleosis-
like Sx: fever, sore throat, rash, malaise, lymphadenopathy, diarrhea,
etc.
 List of symptoms of HIV/AIDS:
 Early infection:
 more common to develop a brief flu-like illness two to
four weeks after becoming infected. Signs and symptoms
may include:
 Fever
 Headache
 Sore throat
 Swollen lymph glands
 Rash
 Later infection :
 may remain symptom-free for eight or nine years or
more
 you may develop mild infections or chronic symptoms
such as:
 Swollen lymph nodes — often one of the first signs of
HIV infection
 Diarrhea
 Weight loss
 Fever
 Cough and shortness of breath
 Latest phase of infection : (AIDS) :
 HIV-antibody test plus at least one of the
following:
 The development of an opportunistic
infection — an infection that occurs when
your immune system is impaired — such as
Pneumocystis carinii pneumonia (PCP)
 A CD4 lymphocyte count of 200 or less — a normal
count ranges from 800 to 1,200
 The signs and symptoms of some of these infections
may include:
 Soaking night sweats
 Shaking chills or fever higher than 100 F (38 C) for
several weeks
 Dry cough and shortness of breath
 Chronic diarrhea
 Persistent white spots or unusual lesions on your
tongue or in your mouth
 Headaches
 Blurred and distorted vision
 Weight loss
 You may also begin to experience signs and
symptoms of later stage HIV infection itself, such
as:
 Persistent, unexplained fatigue
 Soaking night sweats
 Shaking chills or fever higher than 100 F (38 C) for
several weeks
 Swelling of lymph nodes for more than three
months
 Chronic diarrhea
 Persistent headaches
 If you're infected with HIV, you're also more likely
to develop certain cancers, especially Kaposi's
sarcoma, cervical cancer and lymphoma
 Symptoms of HIV in children :
Children who are HIV-positive may experience:
 Difficulty gaining weight
 Difficulty growing normally
 Problems walking
 Delayed mental development
 Severe forms of common childhood illnesses such
as ear infections (otitis media), pneumonia and
tonsillitis
 AIDS defining conditions:
 Encephalopathy, HIV-related
 Pneumonia, recurrent (leading cause of death)
ELISA (Enzyme Linked Immuno-Sorbent Assay): Done
to detect HIV antibodies in patient’s serum (antigens
used are p24, p17, gp160, gp120, and gp41).
Anti-p24 is the first reliably detected antibody but
declines as viral titres rise in late infection
Envelope antibodies rise more slowly but stay high at
the end
Env antigens show major antigenic variation
ELISA for p24 useful early
Western blot for antibodies specific to HIV
Immunoelectrofluorescence
HIV DNA PCR (Polymerase Chain Reaction):
Qualitative to detect HIV infection in
newborns of mothers are HIV+
Quantitative HIV DNA PCR to determine viral
load to assess treatment
Culture for HIV (with antigen detection in
culture) :
HIV infection in newborns whose mothers are
HIV+
To assess drug resistance
HAART: Highly Affective Anti-Retro Viral Therapy: Physicians
consider 200 to 350 CD4 cells/mm3 as the range to consider
starting HAART (Highly Active Antiretroviral Therapy).
HAART combines two types of antiretroviral drugs
RTI’s (Reverse Transcriptase Inhibitors): Zidovudine (AZT/ZDV),
Didanosine (DDI), Zalcitabine (DDC), Stavudine (D4T),
Lamivudine (3TC)
NNRTI’s (Non-Nucleoside RTI’S) : Delavirdine, Nevirapine,
Efavirenz
Protease Inhibitors: Indinavir, Ritonavir
For needle stick:
ZDV+3TC 1 month, but in high risk (high viral RNA copies) a combination
of ZDV+3TC+Indinavir
Pregnancy:
ZDV full dose, trimester 2 and 3+ 6 weeks to neonate reduces vertical
transmission by 80%
ZDV restricted to intrapartum period/NEVIRAPINE-1 dose at onset of
delivery+one dose to neonate
Symptomatic tx and antibiotics/antivirals/glucocorticoids/thalidomide
/antifungals/metronidazole for bacterial, viral, autoimmune, fungal and
parasitic infections.
Vienna, Austria
July 18-23, 2010
The Vienna Declaration is a scientific statement seeking to improve community
health and safety by calling for the incorporation
of scientific evidence into illicit drug policies.
“…that drug law enforcement has failed to achieve its stated objectives, its
harmful consequences must be acknowledged…”
◦ “HIV epidemics fueled by criminalisation.. and by prohibitions on provision of
sterile needles and opioid substitution treatment.”
◦ “..undermining of public health systems when law enforcement drives
drug users away from prevention and care services…”
◦ “A crisis in criminal justice…”
◦ “Severe human rights violations…including execution.. in a number of countries.”
“We the undersigned, call on governments and international organizations
to:”
• “address the individual and community harms stemming from illicit drug use.”
• “Decriminalise drug users, scale up … treatment options…”
• “endorse and scale up funding for the comprehensive package of HIV interventions spelled out in
the WHO, UNODC, and UNAIDS Target Setting Guide.”

www.viennadeclaration.com
33.4 MILLION PEOPLE LIVING WITH HIV

40% KNOW THEIR STATUS


2 MILLION
DEATHS THIS YEAR
5 million on therapy

10 million waiting for therapy

2.7 MILLION
NEW INFECTIONS

UNAIDS Outlook Report | 2010


N Africa, Middle East,
Caribbean, Oceana
700,000 Latin America
E Europe 2 million
1.5 million
India North America, W & C Europe
Asia 4.7 million 2.4 million US 1.2 million 2.3 million

SUB-SAHARAN AFRICA: 22.4 MILLION


Nigeria
Tanzania
2.6 million
1.4 million
Zimbabwe
1.3 million (15.3%)
Zambia South Africa
1.3 million (15.%2) 5.7 million
(18.1%)
Mozambique
2.4 million

UNAIDS Outlook Report | 2010


Rate of HIV Infection (Month 54)
 Extended follow-up of Kenyan P=0.0007

immediate vs. delayed


circumcision trial (N=2784) 2.45

◦ 60% protection reported

# per 100 PY
 Trial unblinded 12/2006 and
circumcision offered to all 0.91
 89% reconsented to participate
in long-term follow-up study
◦ 767 circumcised (Circ)
◦ 785 uncircumcised (Uncirc)
Circ Uncirc
◦ Uncircumcised offered Cumulative
circumcision throughout follow- Incidence (%) 4.0 10.6
up
RR = 0.36, 95% CI 0.24, 0.55

Bailey RC, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. FRLBC101.
 Randomized, double-blind, placebo controlled trial of
Quadrivalent (6/11/16/18) HPV vaccine
• 3 doses (0, 2, 6 months)
 3,463 men ages 16-23; 602 MSM ages 16-26
• 1-5 partners in past year
• No history of genital warts
Per protocol analysis*
%
Quad 95%
Efficac
Population, endpoint vaccine Placebo CI
y
Cases Rate Cases Rate
All subjects, external genital 3/1397 0.1 31/1,408 1.1 90.4 69.2, 98.1
lesions
MSM, 6/11/16/18-related 5/299 1.3 24/299 5.8 77.5 39.6, 93.3
AIN
4.1
MSM, persistent HPV 0.6 per
AIN = anal intraepithelial neoplasia
15 after month 7.
* Completed 3 injection series within time windows, endpoint 101 per 85.6 73.4, 92.9
6/11/16/18 DNA 100 PY
Jessen H, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB101. 100
TDF gel 1% Completed
• Two sites in Kwa-Zulu 40 mg PMPA 422 (94.8%)

Natal, SA: rural & urban Analyzed


445 Endpoints
• Sexually active women,
HIV-1 infection
ages 18-40 not using Applicators returned to
Randomized Safety
barrier contraception measure adherence
1085 HSV-2 infection
• Estimated HIV incidence
rate of 15.6% and 11.2%
placebo Completed
421 (94.8%)
Screened Analyzed
2160 444

Administration of TDF gel:


•Insert 1 dose within 12 hours Before sex

•Insert 1 dose ASAP, within 12 hours After sex

•No more than 2 doses within 24 hours

Abdool Karim Q, et al. 18th IAC; Vienna, July 18-23, 2010; Abst TUSS0502; Kashuba A, et al. ibid. Abst. TUSS0503; Sokal D, et al. ibid. Abst.
TUSS0504.
CVF Concentrations were Lower, and Detected
HIV Infections Over Time1 Less Frequently in HIV+ Women3
109 Tenofovir Gel Placebo
108
Placebo HIV+ HIV- Placebo

TFV Concentration (ng/mL)


107 1 (0-290,734) 520 (0-1,338,079) 0 (0-4,4)
P=0.017 106
Tenofovir 105
104
103
102
101
100
Months of 6 12 18 24 30
Proportion with 45% 96% 7%
Detectable Concentrations
Follow-up Time post reported 4.5 (1-24) 4.5 (2-28) 6 (1-34)
Effectiveness 47% 50% 43% 40% 39% gel use (days)
(P- value) (0.069) (0.007) (0.004) (0.013) (0.017)

Safety
• No TDF resistance
TDF prevents incident HSV • No evidence for renal or bone toxicity
infections2 • Increased rate of mild diarrhea in TDF
group (17% vs. 11%)
 HSV infection rate: 29/202 vs. 48/224; • No adverse outcomes with pregnancies
 IRR 0.49 P=0.003

1. Abdool Karim Q, et al. 18th IAC; Vienna, July 18-23, 2010; Abst TUSS0502; 2. Kashuba A, et al. ibid. Abst. TUSS0503; 3. Sokal D, et al. ibid. Abst. TUSS0504.
Single Dose TDF PK in Blood Plasma, Phase 2 Safety Trial of
Rectal Tissue and CV Fluid1 TDF PrEP in MSM2
 Evaluate safety of TDF PrEP
1000 Blue = Rectal
RT Tissue
and risk behaviors
HIV(-) MSM at 3 sites
Blood Plasma
Red = PBMC 
100

10
◦ TDF 300 mg QD
1
◦ PLC
◦ 9 mo. delay – TDF 300 mg
0.1
0 2 4 6 8 10 12 14
◦ 9 mo. delay – PLC
Time Post Dose  Results
(Days)
◦ No difference in AEs,
1000 Cervicovaginal Fluid including renal
Purple Blood
= CVFPlasma
100 Red = PBMC ◦ No increase in risk behavior
10 ◦ 7 infections, 1 infected at
1
baseline, 3 PLC, 3 during
delay period
0.1
0 2 4 6 8 10 12 14
Time Post Dose
(Days)
1. Patterson K, et al. 18th IAC; Vienna, July 18-23, 2010; Abst THBS0304; 2. Glohskopf L, et al. ibid. Abst. FRLBC102.
Estimated
Target
Trial
Trial Product Population Sites
CDC Bangkok 2,400 Completion
TDF Thailand 1 Q, 2011
st

tenofovir IDUs
Peru, Ecuador,
3,000
iPREX TDF/FTC US, 1st Q, 2011
MSM
S Africa and
TDF & 4,700 Brazil
Partners PrEP Kenya, Uganda 2013
TDF/FTC discordant
couples
TDF gel, Malawi, South
5,000
VOICE TDF & Africa, Uganda, 2013
women
TDF/FTC Zambia,
Zimbabwe
Kenya, Malawi,
TDF & 3,900
FemPrEP South Africa, 2013
TDF/FTC women
Tanzania,
Abdool Karim S, et al. 18th IAC; Vienna, July 18-23, 2010; Abst THBS0305.
HIV Positive MSM Alive
 Background Newly Infected
HIV Transmission Rate pr 100 HIV Positive MSM
◦ Denmark: 5.5 million people

Transmission Rate Pr 100 HIV Positive MSM


with a national medical record 12,0

HIV Positive MSM Alive/Newly Infected


database
◦ 2,500 cases of HIV among MSM, 10,0
estimated 220/100,000
◦ 77% of MSM have been HIV 8,0
tested
◦ HIV testing and ARVs are free
◦ >80% of MSM diagnosed are on 6,0

treatment, with 85% having


undetectable viral load 2,0
 Objective: evaluate rate of HIV
transmission given stable 0,0
number of new diagnoses and
increased survival
◦ Constant number of 110-120 • Decreased transmission rate not
new infections among MSM due to less risky sex – increasing
yearly since 1995, despite more unprotected sex among MSM with
people living with disease discordant HIV or unknown status

Cowan S, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAC0103.
ARVs may not always prevent transmission among discordant couples 1
 Open label ART vs. observation off therapy for infected partner among 1927 discordant couples in China
 71% of index cases on therapy
 Transmissions: 84 (4.3%); 1.71 / 100 CY

Virologic suppression not always achieved in every population 2


 Study of virologic suppression rates among drug users in Vancouver

N Infections RR 95% CI
On ART 130 66 0.76 0.45-1.28
3
Off ART 540 18 1.00

Factors associated with time to virologic suppression


(Relative hazard ratio)

Baseline CD4+ count 0.90 (0.84-0.96; P<0.001)


Baseline viral load 0.86 (0.73-1.00; P-0.064)
Crystal meth injection 0.63 (0.40 – 0.98; P=0.039)
1
1. Ge Z, et al. 18th IAC; Vienna, July 18-23, 2010; Abst THPDC102; 2. Fairbairn N, et al. ibid. Abst. MOAC0405.
 Model of cost effectiveness for expanded testing and ARV treatment under
several scenarios in South Africa1
40 Year Projections
Current <350 <500 Universa
l
Person yrs ART (millions) 79 109 131 134
New HIV infections (millions) 8.7 7.3 5.7 4.0
Deaths (millions) 12.5 10.6 8.7 7.1
HIV costs (billions) 75.3 71.5 66.5 61.5
 Treatment as Prevention: the Test and Treat Movement 2
◦ NIH funded, Botswana Cohort Pilot (Essex)
◦ HPTN 065 in US: NYC and Washington, DC (El-Sadr, Mayer)
◦ Population ART in Tanzania (Fiddler, Hayes, Watson-Jones)
◦ HPTN concept in development for Africa (Mastro, Hodder)
◦ Kenya (Little)
◦ ANRS (Hirschel and Dabis)

1. Kahn JG, et al. 18th IAC; Vienna, July 18-23, 2010; Abst MOAE0405; 2. Cohen M, et al. ibid. Abst. WESY0705.
Rick Elion, MD
Associate Professor, George Washington University
School of Medicine
Washington, DC
Measure Recommendation
Specific conditions
Symptomatic HIV disease
Pregnancy
High HIV-1 RNA Level (>100,000 copies/mL)
Rapid CD4 count decline (>100 cells/mm3 per ART recommended
year)
Active hepatitis B or C* virus co-infection regardless of CD4 cell count
Active or high risk for cardiovascular disease*
HIV-associated nephropathy
Symptomatic primary HIV infection*
Risk for secondary HIV transmission is high*

CD4 cell count ≤500 cells/mm3 ART recommended


CD4 cell count >500 cells/mm3 ART should be considered§

* Differs from 2009 DHHS guidelines


§
Unless patient is an elite controller (HIV-1 RNA <50 copies/mL) or has stable CD4 cell count and low-level viremia in the absence of ART

Thompson MA, et al. JAMA 2010;304(3):321-333; US Department of Health and Human Services Guidelines; Revised December 1, 2009.
Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
 Evaluation of clinical benefit of Cum. Risk (%)
HAART initiation vs. deferral in CD4 Count
AIDS-free, HAART-naïve HIV (cells/mm3 RD NNT
Defer Initiate
seroconverters with CD4 ) (95%CI) (95%CI)
<800 cells/mm3 (N=9,455)
◦ 23 clinical cohorts (1/96 to 5/09) -30.0 3
0-49 46.6 16.6
◦ 78% male: 56% MSM (-45.1, -15.0) (2, 7)
◦ HIV(+) 1.3 yrs (IQR: 0.8-3.4) -15.0 7
50-199 20.7 5.7
 After 52,268 person years (-19.7, -10.3) (5, 10)
follow-up (median 4.7 yrs),
1,356 met endpoint of AIDS/Death 200-349 -4.8 21
10.3 5.5
or all-cause mortality (-7.0, -2.6) (14, 38)
◦ 812 (8.6%) developed AIDS -2.9 34
◦ 544 (5.8%) died 350-499 6.3 3.4
(-5.0, -0.9) (20, 115)
 Conclusion: HAART initiation at 0.3
CD4 <500 cells/mm3 associated 500-799 4.9 5.2 ∞
(-3.7, 4.2)
with lower risk
RD = cumulative risk difference at 3 years
NNT = number needed to treat to prevent 1 new case of AIDS or
death w/in 3 yrs
Funk MJ, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB201.
 Randomized, prospective study
comparing early (2 weeks) vs. late (8 Kaplan-Meier Survival Estimates
1.00
weeks) ART for patients with newly
diagnosed TB starting TB therapy (n=
661) 0.75
P<0.0
• Baseline median CD4 25 cells/mm3 and
1
HIV RNA 5.6 log10 c/mL
 Results 0.50

◦ Early ART strategy significantly improved


survival
◦ More IRIS in early ART arm but most 0.25
Early Late
cases minor
◦ Virologic suppression in >95% at 150
weeks 0.00
0 50 100 150 200
 Results of study confirm benefits of
early ART in patients with acute OIs Weeks After Randomization

Blanc F, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB106.
+

Comparison to 2009 DHHS Guidelines:


• “Recommended” therapies are the same as “Preferred” regimens
• In addition to “Alternative” therapies listed, 2009 DHHS Guidelines “Alternative” and
“Acceptable” regimens include ZDV/3TC, ddI + 3TC, NVP, unboosted ATV, and SQV/r

Thompson MA, et al. JAMA 2010;304(3):321-333; US Department of Health and Human Services Guidelines; Revised December 1, 2009. Available at:
http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
48 weeks 96 weeks
primary analysis final analysis

ECHO (TMC278-C209)
RPV 25mg QD + TDF/FTC (n=346)
N=690 patients 1:1
EFV 600mg QD + TDF/FTC (n=344)

THRIVE (TMC278-C215)
RPV 25mg QD + 2NRTIs* (n=340)
N=678 patients 1:1
EFV 600mg QD + 2NRTIs* (n=338)
* Investigator’s choice: TDF/FTC; AZT/3TC; ABC/3TC

 Inclusion criteria: viral load (VL) ≥5K; no NNRTI RAMs; sensitivity to the NRTIs
 Primary objective: demonstrate non-inferiority (12% margin) vs. EFV in confirmed
virologic response (VL <50 copies/mL, ITT-TLOVR) at Week 48
 Stratification factors by screening VL (both) and NRTI background (THRIVE only)

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
RPV EFV
Baseline parameter
N=686 N=682
Female 25% 24%
Median age (years) 36 36
Race
Caucasian 61% 60%
Black 24% 23%
Asian 11% 14%
Other races/not allowed to ask 3% 3%
Median log 10 VL, copies/mL (min–
5 (2–7) 5 (3–7)
max)
Baseline VL >100,000 copies/mL 46% 52%
Median CD4 cells/mm 3 (min–max) 249 (1–888) 260 (1–1,137)
Hepatitis B or C co-infection 7% 9%

• NRTI Background regimen (THRIVE) was balanced between treatment groups


– TDF/FTC 60%; AZT/3TC 30%; ABC/3TC 10%

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
Percent <50 copies/mL
RPV 25mg QD (N=686)
100 EFV 600mg QD (N=682)
Virologic responders (%, 95% CI)

84.3%
80 82.3%

60

p value for non-inferiority at 12% margin


40 (84.3% vs. 82.3%) P<0.001

RPV CD4 Mean Δ +192 cells/mm3


20 EFV CD4 Mean Δ +176 cells/mm3

0
0 2 4 8 12 16 24 32 40 48
Time (weeks)
Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
Percent <50 copies/mL EFV 600mg qd
RPV 25mg qd
6.6
6.6 (1.6,
(1.6, 11.5)*
11.5)*

–3.6
–3.6 (–9.8,
(–9.8, 2.5)*
2.5)*
Virologic responders (%)

90% 91%

Virologic responders (%)


90%
83% 84% 84% 82% 81%
79% 80% 77%
76%

162/ 136/ 170/ 140/ 332/ 276/ 125/ 149/ 121/ 136/ 246/ 285/
181 163 187 167 368 330 165 181 153 171 318 352

≤100,000 copies/mL >100,000 copies/mL

• Greater number of virologic failures seen with RPV (62 vs. 28) compared to EFV
• No difference seen in efficacy based on NRTI backbone, gender, race or region

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
RPV EFV

Virologic failure with resistance data 62 28

No NNRTI or NRTI RAMs 29% 43%

Emergent† NNRTI RAMs 63% 54%

- most frequent NNRTI RAM E138K K103N

Emergent† NRTI RAMs 68% 32%

- most frequent NRTI RAM M184I M184V

• 31/62 (50%) of virologic failures on RPV were resistant


phenotypically to RPV
– Of these, 90% were phenotypically cross-resistant to
etravirine
† Determined in the ITT population with all available data, regardless of time of failure and reason for discontinuation.
‡ At least one emergent NNRTI (Antivir Ther 2009;14:103–9 ) or NRTI (Top HIV Med 2009;17:138–45) RAM.

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
RPV EFV P value RPV
Incidence, %
N=686 N=682 vs. EFV

Median treatment duration (weeks) 56 56


Any serious AE 7 8 NS
Any AE 90 92 NS
Any grade 2–4 AE at least possibly related to 16 31 <0.0001
treatment
Discontinuations due to AEs 3 8 0.0005
Most common AEs of interest
Any neurological AE 17 38 <0.0001
Dizziness 8 26 <0.0001
Any psychiatric AE 15 23 0.0002
Abnormal dreams/nightmares 8 13 0.0061
Rash (any type) 3 14 <0.0001
Minimal change in mean serum creatinine in both groups (RPV <0.1 and EFV 0 mg/dL)
No changes seen in QtC interval

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
Paul Sax, MD
Associate Professor, Harvard Medical School
Boston, MA
Double-blind, double-dummy, non-inferiority study. 1:1 randomization to 400 mg XR QD
vs. 200 mg IR BID after a 14-day IR lead-in 200 mg QD dose (given to all patients);
FTC/TDF fixed-dose background
Parameter Nevirapine IR Nevirapine XR
Number of patients 508 505
Median Baseline HIV-1 RNA (log10
4.7 4.7
copies/mL)
Mean CD4+ cell count (cells/mm3) 227 229
History of AIDS 26% 30%
7000
Nevirapine Plasma (ng/mL)

200mg Nevirapine IR BID (n=25)


400mg Nevirapine XR QD (n=25)
6000

5000

4000

3000

2000
0 4 8 12 6 20 24
Time (hours)
Gathe J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB202.
Parameter Nevirapine IR Nevirapine XR
VL <50 copies/mL
100 Number of patients 506 505
Adjusted difference : 4.92% in favour of XR (−0.11,
Any AE 89.3% 87.7%
Virologic responders (%, 95% CI)

9.96)
80 AEs leading to
8.9% 6.3%
discontinuation
Serious AEs 10.7% 11.5%
60
Deaths 1.0% 0.2%

40 Drug-related AEs 24.3% 19.8%

Nevirapine IR 75.89%
20  Non-inferior efficacy for XR QD to IR BID
Nevirapine XR 80.99%
 Similar efficacy noted across many
PK strata indicating adequate trough drug
0 2 4 6 8 12 16 24 32 40 48 exposure for XR dosing
Weeks  Similar safety and tolerability for both
formulations
◦ Favorable lipid changes as in prior NVP studies
◦ 5 cases of Stevens-Johnson syndrome (occurred
in both arms), none fatal

Gathe J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB202.
FPV/r + EFV + ABC/STC
Baseline Characteristics ABC/3TC (n=50)

Prospective, open-label study


(n=51)
 Female 31% 32%

comparing FPV/r (1400/100 Race:


African American/African 55% 66%
mg) QD and EFV, with White 24% 18%

ABC/3TC as NRTI backbone Mixed race


Ethnicity:
16% 10%

 Target population: ARV-naïve, Hispanic or Latino 41% 34%

minority populations
Median HIV-1 RNA, log10 c/ml 5 4.8
≥100,000 c/mL 43% 40%
Results (24 week subanalysis) Median CD4 cell count, cells/mm3 237 272
<200 cells/mm 3
41%(M/D=F)
Virologic Results 34%
 Similar virologic efficacy 100 88%
88%

 Virologic failures: 1 FPV/r vs.

Percentage of Subjects
80 84%
78%

3 EFV 60
 CD4 Δ: EFV 145 vs. FPV/r
134 cells/mm3 40

 Adverse Events G 1-2: EFV 28%


HIV-1 RNA <400 c/mL, FPV/r
20 HIV-1 RNA <400 c/mL, EFV

vs. FPV/r 18%; G 3-4 similar HIV-1 RNA <50 c/mL, FPV/r
0 HIV-1 RNA <50 c/mL, EFV

0 2 4 8 12 24
Study Week
Kumar P, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE0111.
 Single-arm, open-label study of ABC/3TC + RAL (N=35)
◦ Treatment-naïve
◦ HLA-B*5701 negative
◦ No baseline resistance to ABC or 3TC
HIV RNA <50 Copies/mL Change from Baseline in CD4 Cell Count

100 350

Median (Q1-Q3) Change from


Percentage of Subjects

300
80

Baseline (cells/mm3)
250 +247
60
200

40 150
100
20
Observed 20
M/D-F
0 0
BL2 4 8 12 16 24 36 48 BL 4 8 12 16 24 36 48
Study Week Study Week
 Statistically significant increases in median fasting total, HDL, and LDL
cholesterol; total/HDL ratio and TG remained stable
 No suspected HSR or significant increases in CRP or IL-6
 One case of virologic failure due to transmitted integrase resistance
detected on retrospective testing

Young B, et al. 18th IAC; Vienna, July 18-23, 2010; Absts. THPE0112 and THPE0163.
HIV-1 infection
ARV-naïve
Week 48 Week 96
HIV-1 RNA >1000 c/mL
LPV/r 400/100 mg BID Primary
Any CD4+ T-cell count
+ TDF/FTC 300/200 mg QD Efficacy
(n=105) Endpoint

Baseline Characteristics
LPV/r +RAL LPV/ r +
Variable
(n=101) TDF/FTC
(n=105)
Mean age (years) 40 39
Males 87% 82%
White 73% 77%
Black 22% 21%
Mean HIV-1 RNA (log10 copies/mL) 4.24 4.25
Mean CD4 (cells/mm3) 289 298
Reynes J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0101.
HV RNA <40 copies/mL (ITT-TOLVR)
100 84.8%
90 *
* 83.2%
80
Proportion of subjects

70 * 95% Cl = -12% to 8.8%


60

50

40 *
30 LPV/r + RAL

20 LPV/r + TDF/FTC
* Statistically significant difference between groups:
10 Weeks 2, 4, 8 P<0.001
Week 16 P=0.038
0
0 8 16 24 32 40 48

Weeks

• Adverse event rate similar


• Additional analyses planned: Adherence, DEXA scans (fat/bone),
anthropometric measurements, patient reported outcomes
Reynes J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0101.
HIV RNA 5000 c/mL
Randomization Stratified: HIV RNA <100,000 c/mL vs. 100,000 c/mL

(2:1)
ATV + RAL 300/400 mg BID ATV/r 300/100 mg QD +
(n=63) TDF/FTC 300/200 mg QD (n=31)

4.9 Mean BL HIV RNA log10 c/mL 4.9

54% Baseline HIV RNA ≥ 100,000 c/mL 43%

256 Mean CD4 (cells/mm3) 261

Kozal M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB204.
HIV RNA < 50 c/mL through Week 24 (NC = F)
 ATV + RAL (n=63)
100  ATV/r + TDF/FTC (n=30)
Percent Responders (95% Cl)

80
74.6%

60 63.3%

40

20 Mean CD4 change from baseline:


ATV + RAL: 166 cells/mm3
ATV/r + TDF/FTC: 127 cells/mm3
0
B/L 4 8 12 16 20 24

• Response rates (HIV RNA <50 c/mL) for ATV + RAL at primary
endpoint (week 24) were consistent with current standard of care
• Through week 24, 4 patients on ATV + RAL developed genotypic
and phenotypic resistance to RAL
• Grade 4 Hyperbilirubinemia rates higher than with
ATV + RAL (21% vs. 0%)
Kozal M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB204.
Open-label, 48 week phase 2b study

TDF/FTC + ATV/r (300/100 mg QD)


Randomization
1:1
(N=121) MVC (150 mg QD) + ATV/r (300/100 mg
QD)
16 wk 24 wk 48wk
Interim Analyses Primary Analysis

Patient eligibility criteria:


 R5 HIV at screening

 HIV-1 RNA ≥1000 copies/mL

 CD4 ≥100 cells/mm3

 No evidence of resistance to ATV/r, TDF, or FTC

Mills A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB203.
HIV-1 RNA < 50 copies/mL Adverse Events
100
MCV TDF/FT
90 89%
TDF / FTC + C
Percentage of Patients Responding

MVC 80%
80
ATV/r + ATV/r
70 Any Aes 93% 93%
60 Serious Aes 8% 16%
50 Grade 3 or 4 AEs
33% 21%
40

Grade 3 or 4 AEs related to


30 26% 13%
20
hyperbilirubinemia
Grade 3 or 4 laboratory
10 59% 49%
hyperbilirubinemia
0
Discontinued due to AE 3% 0
0 2 4 6 8 10 12 14 16 18 20 22 24

Study Week

• 5 MVC and 1 TDF/FTC switched to DRV per protocol for jaundice and/or scleral icterus
• No resistance seen in either arm, and no change in phenotypic tropism result

Mills A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB203.
Calvin Cohen, MD
Research Director, CRI New England
Harvard Vanguard Medical Associates
Boston, MA
Inclusion Criteria
 Taking 2 NRTI + either NNRTI or boosted PI at screening (stratified)
 HIV RNA <50 copies/mL for ≥6 months
 No prior use of darunavir (DRV)
 No history of virological failure

 Primary Endpoint: Virologic Failure at week 48 (TLOVR)


 Secondary Endpoint: Week 96 analysis

DRV/r 800/100 mg QD
+ 2 NRTI (re-optimized at baseline)
(n=129)

256 subjects

DRV/r 800/100 mg QD
(n=127)

144 weeks

Rieger A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB209.
TLOVR, S=F Switch included
100
Diff = -5.8% (-16.0%, +4.4%) Diff = +1.4% (-5.5%, +8.3%) Multivariate Analysis
92.1%
90.7%
90
RR
Comparison
HIV RNA <50 by Week 96 (%)

80.6% (95% CI, p value)


74.8%
80
DRV/r vs. 1.17
70
DRV/r + 2NRTI (0.61 – 2.25, n.s.)
60
HCV co- 4.35
50
infection (2.06 – 9.17,
40 <0.0001)
• Rates of double HIV RNA blips
30
and discontinuations were
20 slightly higher in the DRV/r
monotherapy arm
10
• 1 in each arm with >1 PI
0 mutation, no phenotypic
DRV/r + 2NRTI DRV/r mono DRV/r + 2NRTI DRV/r mono resistance seen
n=129 n=127 n=129 n=127

Rieger A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB209.
 Single-arm, Pilot Simplification Study (N=40)
 Inclusion criteria:
◦ Patients on ATV/r + 2 NRTIs >3 months (97.5% on TDF)
◦ HIV-RNA <50 copies/mL >3 months
◦ CD4 >200 cells/mm3 >6 months
 Exclusion criteria:
◦ History consistent with possible resistance to 3TC or atazanavir
◦ Proton pump inhibitor use
◦ HBsAg positive
 Baseline Characteristics
Age (median, years) 45
Male sex 57.5%
Injecting drug users 22.5%
HCV co-infection 20%
Time (median, years) from starting last cART 2.6
regimen
CD4 cells count (median, cells/mm3) 598
De Luca A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB207.
 Virologic Results: All maintained HIV RNA <50 copies/mL, without
blips
 Lipid Changes Through Week 24:

P<0.01 for all parameters


Mean change (mg/dL)

+21 at all time points


+20
+18
+17

+13

+9

+4 +4
+3

 Week 24 Renal Outcomes: Creatinine decrease of 0.08 (P<0.001);


GFR increase 6 ml/min by MDRD (P<0.001)

Conclusion: If week 48 results consistent, phase III randomized studies planned


De Luca A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB207.
Phase IIIb, randomized, open-label study
Treatment phase (up to 48 weeks)
• ARV-exp’d pts aged 18
years DRV/r 800/100mg QD + OBT (n=294)
• HIV-1 RNA >1000 copies/mL
• CD4 cell count >50 cells/mm3
• No DRV RAMs at screening DRV/r 600/100mg BID + OBT (n=296)
• Stable HAART for 12 weeks

Pill Count Results: At all timepoints, the % of adherent pts was numerically
higher on QD DRV/r (58%-63%) vs. BID (42%-59%); at week 4, P<0.0001.
Virological response (HIV-1 RNA <50 copies/mL) at Week 48 by adherence
measure
DRV/r DRV/r DRV/r QD– DRV/r BID
800/100mg QD 600/100mg BID % Difference in response (95%
CI)
Adherence measured by M-MASRI
Adherent 84.9% 85.2% -0.3 (-8.2; 7.6)
Suboptimally adherent 56.7% 62.2% -5.5 (-18.7; 7.7)
Adherence measured by pill count
Adherent 82.2%
Workman C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUPE0184.
83.8% -1.5 (-9.7; 6.7)
Significant predictors of response
•Baseline viral load (P=0.0014)
•Adherence (M-MASRI) (P<0.0001)
•Presence of M184V/I at baseline (P<0.0001)
 DRV/r 800/100mg
qd
 DRV/r 600/100mg
bid

Patients with HIV-1 RNA


Patients with HIV-1RNA

<50 copies/mL (%)*


<50 copies/mL (%)*

Presence of M184I/V mutation at baseline Number of IAS-USA§ primary PI mutations at baseline

Cahn P, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. LBPE15.
• Phase IIb dose-ranging, partially-blinded trial (N=205)
• Primary endpoint: % <50 copies/mL at 16 weeks (TLOVR)

572 10 mg 572 Selected Dose


Treatment-Naïve
HIV-1 RNA >1000c/mL, 572 25 mg after Week 48
1:1:1:1 Randomization 572 50 mg
(N=205) EFV 600 mg EFV 600 mg

Baseline HIV-1 RNA


Mean (log10 copies/mL) 4.46
>100,000 copies/mL 21%
Mean Baseline CD4+ (cells/mm 3) 324
Investigator-selected NRTIs
TDF/FTC 67%
ABC/3TC 33%
Arribas J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB205.
572 572 572 EFV
10mg 25mg 50mg 600mg
(n=53) (n=51) (n=51) (n=50)
<50 Copies/mL (TLOVR) at Week 16 96% 92% 90% 60%
Reason for non-response (virologic)
DC for insufficient viral load response 2% 0 0 0
Never suppressed by Week 16 2% 4% 4% 30%
Rebound 0 0 2% 0
Reason for non-response (discontinuations)
Adverse event (discontinued) 0 2% 0 8%
Lost to follow-up / Other 0 2% 4% 2%

 Events leading to withdrawal:


◦ GSK 572 (n=1): dyspepsia
◦ EFV (n=4): abnormal dreams, suicide attempt, drug intolerance,
drug hypersensitivity
 Conclusion: GSK 572 once-daily was generally well tolerated,
with potent antiviral activity at all doses explored; 50 mg entering Phase III
Arribas J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB205.
 Virologic failure may occur with raltegravir use
◦ 23% in BenchMRK 1 and 2
 3 RAL resistant pathways identified
◦ Y143, N155, Q148
 GSK 572 in vitro appears active against some pathways
◦ Minimal cross resistance from N155 and
Study Y143 (Cohort I)
Design
•Current or historic RAL-failures with evidence of RAL-resistance
•At least 3 ART-class resistant (includes INI)
•All subjects receive S/GSK1349572 (50mg QD)

Q148H/K/R + one or more secondary resistance


mutations* (N~15)
Allocated to one of
two groups based on Functional Monotherapy Phase Continuation
genotype at screen Replace RAL with S/GSK1349572 or add, if RAL already
stopped
Phase
to ensure broad S/GSK1349572 + OBR
sensitivity range
All other mutations (including codon 148 single
mutation)** (N~15)
Day 1 Day 11 Week 24

* Q148H/K/R plus changes in L74 and/or E138 and/or G140


** N155H and Y143H pathways or Q148H/K/R single mutants
Eron J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0105.
Plasma HIV-RNA Response at DAY 11 by Viral IN Baseline Genotypic
Profile
Primary End-Point Secondary End-Point
HIV-1 RNA <400c/mL or ≥0.7 log13c/mL decline Change in HIV-1 RNA log10 c/mL
Mean (SD)
All subjects 21/27 -1.45
(78%) (0.76)
Q148H/K/R + ≥1 Q148 3/9* -.072
associated mutations at (33%) (0.63)
L74, E138 or G140 (n=9)
All other genotypes from 18/18 -1.82
N155H and Y143H pathways
 Drug related AEs: 4 (15%) subjects (100%) (0.53)
(n=18)
◦ Grade 1: diarrhea & nausea (n=1), anemia (n=1)
◦ Grade 2: fatigue & insomnia (n=1), diarrhea (n=1)
 Grade 3 laboratory toxicities: 6 (22%) subjects
◦ 1 amylase increase
◦ 1 total cholesterol increase
◦ 2 lipase increase
◦ 2 phosphorus decrease
* Halted enrollment early in this group due to less robust virologic response

Eron J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0105.
Andrew Zolopa, MD
Associate Professor, Stanford University School of
Medicine
Palo Alto, CA
 Treatment-naïve patients
from STARTMRK study
◦ Patients randomized to
either EFV or RAL, both
given with TDF/FTC
 Genotypes obtained at

Percent of Patients
confirmed virologic failure
◦ NNRTI resistance precedes
or simultaneous with
M184V
◦ Integrase resistance follows
M184V
 Suggests higher genetic
barrier to RAL than EFV

Miller M, et al. International HIV and Hepatitis Drug Resistance Workshop; Dubrovnik, June 8-12, 2010; Abst. 3.
Comparison of Baseline and Week 48
 SHIELD: Pilot Study of
ABC/3TC + RAL in Tx- Genotype Results
Baseline Genotype
naïve patients (N=35)
◦ Resistance testing not PR L10I, V32I, M46I, L63S, A71V, I72V, V77I,
V82A, L90M, I93I/L
performed at baseline
RT K70K/R, Q102N, K103N, V106A, K122E, I142V,
 HIV RNA levels of subject C162S/G, I178L, T200A, R277K, V293I
who failed Tx at 48 weeks IN R20K, V113I, T124A, T125T/A, G140S, Q148H,
◦ Baseline: 77,600 c/mL G193E, V201I, E212A, V234L, D288N
◦ Nadir on Tx: 82 c/mL Week 48 Genotype
◦ Week 48: 591 c/mL PR L10I, V32I, M46I, L63S, A71V, I72V, V77I,
V82A, L90M, I93L
 Retrospective baseline and K70R, V75I, Q102N, K103N, V106V/A, K122E,
week 48 resistance RT I142V, C162S, I178L, M184V, T200A, R277K,
testing: multi-drug A288A/T, V293I, E297E/K
resistance, including IN
R20K, K103K/R, V113I, T124A, T125A, G140S,
Q148H, G193E, V201I, E212A, V234L, S255S/N,
integrase D288N
Red mutations are associated with resistance; Underlined mutations were
not present at baseline but are associated with resistance; Bold mutations
were not present at baseline but are not known to be associated with
resistance
Young B, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUPE0163.
 HIV Infected adults on PI/r with VL <50 for >6 mos
 Randomized (2:1) to RAL 800mg QD or 400mg BID
◦ If <50 c/mL at 3 mos. re-randomized (1:1) to QD or
BID
 Primary Endpoint:Baseline Characteristics
% <50 c/mL at 24 wks
All RAL BID RAL RAL QD p
BID→QD
No. of patients 222 35 38 149 --
Mean age (years) 46 44 46 47 0.14
Mean time under ART (months) 101 100 101 102 0.96
Prior suboptimal ART 42% 31% 32% 47% 0.09
Prior virological failure 68% 66% 68% 68% 0.96
Prior NRTI resistance 33% 34.3% 31.6% 33.6% 0.95
Mean CD4 count (cells/mm 3) 574 535 417 623 0.01
NRTI backbone
ABC+3TC 31% 29% 29% 31% 0.80
TDF+FTC 69%
Vispo E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0102. 71% 71% 69%
Proportion of Patients Experiencing Virological Failure
After Switching to RAL
P=0.14

P=0.48
P=0.18
P=0.45

Prior nRTI resistance strongest predictor of failure


Vispo E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0102.
Time to Treatment Failure
 Pts on stable PI/r ART by Treatment Group
◦ VL <50 copies >6 mos 1

 Randomized (1:1) 0.9


◦ Continue PI/r
◦ Switch RAL 0.8 Log rank P=0.4775

Event-free
 Primary endpoint
◦ % <50 at 48 wks
0.7

 Virologic failures 0.6


RAL

◦ 4 RAL arm
PI/r

◦ 6 in PI/r
Well tolerated w/ few
0 4 8 12 16 20 24 28 32 36 40 44
 48
Weeks

D/C for AE in both


PI/r 134 131 124 121 116
RAL 139 138 132 130 124

arms

Martinez E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0103.
 27 patients who failed Day 11 Change from Baseline in
HIV-1 RNA vs. GSK 572 Fold Change (N=27)
RAL with integrase
(IN) resistance
 Continued on ART and -0.5

RAL replaced with GSK


572 for 10 days then -1.0

allowed to change OBT


 Response at day 11 -1.5

clearly related to Q148 + 2

pattern of IN mutations -2.0 Q148 +1


Mixture

Q148 + other IN
Y143
 N155
-2.5 Other
mutations: No
response to GSK 572 0.5 1.0 2.0 5.0 10.0 20.0

Day 1 S/GSK1349572 Fold


Change
Eron J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0105.
 Prevalence of ETR resistance
using samples sent for testing to Proportion
Monogram Biosciences (MGR) MGR Number of of Samples
ETR WGS Samples (%)
 ETR weighted genotypic score
(WGS) and PhenoSense assessed 0 2,142 39.1
on 14,940 samples
 MGR ETR WGS: Includes
1 787 14.4 67.2%
30 Mutations and score of ≤3 is 2 510 9.3
Susceptible
considered sensitive to ERT
 5 most common ETR mutations: 3 243 4.4
Y181C, V90I, G190A, V106I
and P225H 4 735 13.4
 Among 5,482 (36.7%) samples 5 502 9.2
with resistance to EFV or NVP,
67.2% sensitive to ETR by ≥6 563 10.3
genotype and 76.4% by
phenotype Scores 0-3 denote full ETR susceptibility;
scores ≥4 denote reduced ETR susceptibility

Picchio G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOPDB105.
• 4 of 101 in the RAL arm and 3 of 105 patients in the TDF/FTC arm
had genotype tests conducted

DRUG RESISTANCE LPV/r + RAL LPV/r + TDF/FTC

LPV/r 0/4 0/3

RAL 1/3 N/A

TDF 0/4 0/3

FTC 0/4 1/3

• RAL Resistance (N155H) occurred in one patient at week 48 after


rebounding to >50 copies/mL at week 32

Reynes J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0101.
 Randomized 96 week study of LPV/r monotherapy compared to PI/r + nRTIs
 15 male subjects provided semen samples at baseline and end of study
 Only 1 had detectable seminal HIV RNA
◦ Semen viral load of 260 c/mL (plasma viral load was 850 c/mL)
◦ Resistance pattern in semen was same as plasma – 2 major PI mutations at 46 and 84

Viral Load Serum Serum and Semen NRTI Intensification


CD4 Count (cells/mm3) Genotyping Genotyping (ZDV + 3TC)

900
Conclusion: LPV/r monotherapy effective at maintaining viral suppression in semen and
no evidence of “selective” resistance

800
700
600
500
400
300
200
100
0
set-04 nov-04 jan-05 mar-05 may-05 jul-05 set-05 nov-05 jan-06 mar-06 may-06 jul-06 set-06 nov-06

Nunes E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE0124.
Graeme J. Moyle, MD, MB, BS
Associate Director of HIV Research
Chelsea & Westminster Hospital
London, England
Combined Model*
 Clinical data registry-based cohort
comprising 6517 patients (31% female)
with HIV, 273 Acute MIs and >2
encounters between
Age/10yrs
Female
12/98 and 2/08 in a U.S. healthcare system Non-white
 Demographics, co-morbidities HTN
(hypertension, diabetes, dyslipidemia, DM
chronic kidney disease), medication, CD4, Lipid

and HIV viral load data were obtained CKD


Smoking
 Multivariate logistic regression to assess CD4<200
associations between AMI and each VL>100000
antiretroviral medication ABC
 Adjusted Individual Models: IDV DDI

(OR 1.93; 95% CI 1.04-3.57) and NFV FTC

(OR 1.75; 95% CI 1.02-3.01) significantly


D4T
TDF
associated with AMI NVP
 Combined Model*: Only HTN (OR 1.97; 95% ATV
CI 1.25-3.12) and CD4 count <200 NFV
cells/mm3 (OR 1.74; 95% CI 1.07-2.81) SQV

significantly associated with AMI ART Year

0.1 1 10
*Adjusted for ART, cardiovascular, immunologic and virologic factors
Triant V, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0130.
Risk Ratio Risk Ratio
Study or Subgroup Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI Cochrane meta-analysis of
Clumeck 2001 12.0% 0.20 [0.01, 4.08] MI events in ABC vs.
CNA 2.4% 3.01 [0.12, 73.60] Comparator studies suggest
30024 Not estimable no association with MI
CNAAB3005 2.4% 3.02 [0.12, 73.87]
CNAB3001 7.0% 0.35 [0.01, 8.32] •Included mainly naive and
CNAB3002 Not estimable some switch studies
CNAF3007 4.9% 0.95 [0.06, 14.93] •Comparator is PI is some
Daar 2010 33.5% 0.57 [0.17, 1.95]
studies
ESS100327 Not estimable
ESS40002 1.6% 5.83 [0.24, 141.50] •Follow up ranges from
Martin 2009 4.8% 2.98 [0.31, 28.41] 24->96 weeks
NZTA4002 16.7% 0.14 [0.01, 2.76]
•Included 6617 patients but
Opravil 2002 7.4% 0.31 [0.01, 7.59]
Post 2010 7.2% 0.34 [0.01, 8.17]
only 26 MI events
Smith 2009 Not estimable (11 ABC, 15 Control)
Vibhagool 2004 Not estimable •Findings similar for mortality
Total (95% CI) 100.0% 0.74 [0.39, 1.42] •Findings similar if only TDF
Total events considered as comparator
Heterogeneity: Chi²=7.41, df =10 (RR 0.79 95% CI 0.30-2.05,
0.01 0.1 1 10 100
(P=0.69); I²=0% P=0.63)
Test for overall effect: Z=0.91 (P=0.36) Favors abacavir Favors control
Cruciani M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0121.
40 Cholesterol 1.00 15 HDL cholesterol 0.40

30 0.75 0.30
10

mmol/L

mmol/L
20 0.50 0.20

mg/dL
mg/dL

p≤0.0001†
P≤0.0001 † 5
10 0.25 0.10

0 0 0 0

–10 –0.25 –5 –0.10


024 8 12 16 24 32 40 48 024 8 12 16 24 32 40 48 RPV QD
Time (weeks) Time (weeks)
EFV QD
30 LDL cholesterol 0.75 40 Triglycerides 0.45
30
0.30
20 0.50
20

mmol/L
mmol/L

0.15
mg/dL

10
mg/dL
10 0.25
P≤0.0001† 0 0

0 0 –10
–0.15
–20 P≤0.0001†

–10 –0.25 –30 –0.30


024 8 12 16 24 32 40 48 024 8 12 16 24 32 40 48
Time (weeks) Time (weeks)

No difference between groups in total cholesterol/HDL-C ratio at Week 48


† P value vs. EFV at Week 48 (non-parametric Wilcoxon rank-sum test)

Cohen C, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB206.
ATV + RAL (n=51) ATV/r + TDF/FTC (n=20)

300 Total Cholesterol 100 HDL Cholesterol

HDL Cholesterol (mg/dL)


Total Cholesterol (mg/dL)

250
80
200
60
150
40
100

50 20
B/L Wk 24 B/L Wk 24 B/L Wk 24 B/L Wk 24
200 LDL Cholesterol
LDL Cholesterol (mg/dL)

600 Triglycerides

150 Triglycerides (mg/dL)


400
100

200
50

0 0
B/L Wk 24 B/L Wk 24 B/L Wk 24 B/L Wk 24

Kozal M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB204.
P=0.008 P=0.044
mg/dl

P=0.015

Reynes J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0101.
DRV/r ATV/r
Parameter
Screening Phase (4 weeks) Treatment Phase (48 weeks)
(n=34) (n=31)
Male 85% 87%

Median age (years) 36 35


12-week primary analysis
• 65 ART-naïve
subjects Race
DRV/r 800/100mg QD White 62% 39%
• ≥18 years of
+TDF/FTC 300/200mg QD
age Black 38% 55%
n=34
• VL ≥1000 Asian 0 6%
cps/mL
Ethnicity
• Any CD4
• HIV-1 Hispanic 21% 23%
ATV/r 300/100mg QD
susceptible to Non-Hispanic 79% 77%
+TDF/FTC 300/200mg QD
ATV, DRV, TDF,
n=31 Mean BMI 23.8 24.5
and FTC at BL
resistance test Median CD4+ count
267 316
(cells/mm3)
Mean Viral load (log10 c/mL) 5.0 4.6

Median Viral load (c/mL) 137,000 46,100

Aberg J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0111.
DRV/r ATV/r
Difference
in mean
Change Change change
from from between
BL BL
BL to Wk BL to Wk arms,
Mean Concentrations, mg/dL

12 12 (95% CI)

Glucose, insulin, and HOMA_IR, mean (SD)


Glucose, 89 2 90 6 -4.3
mg/dL (12) (13) (11) (15) (-11.3, 2.8)
1.6 -0.5 2.9 0.1 -0.6
HOMA-IR
(1.7) (2.0) (6.0) (7.5) (-4.1, 2.9)
Creatinine clearance, mean (SD)
Creatinine
107.6 -4.6 110.9 -5.3 -0.7
clearance,
(28.7) (15.6) (27.9) (16.5) (-7.5, 8.9)
mL/min
Biomarkers, mean (SD)
-1.342
3.1 -0.6 2.2 0.7
hs-CRP, mg/L (-4.041,
(5.2) (6.0) (2.5) (4.2)
1.357)
Efficacy parameters, mean (SD)

Difference in
Viral load, 5.0 -3.0 4.6 -2.6 -0.35
13.8 15.7 4.0 4.0 0.06
mean change (-25.8, 53.4) (0.0, 31.3) (-8.6, 16.6) (-1.2, 10.0) (-0.37, 0.50)
log10 cps/mL (0.8) (0.8) (0.7) (0.7) (-0.74, 0.04)
between arms
(95% CI) CD4+ cell 268.3 111.1 326.7 68.3 42.8
count, /mm2 (144.2) (97.3) (174.1) (134.6) (-16.9, 102.6)

Aberg J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0111.
mg/dL

Arribas J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0115.
Martinez E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOAB0103.
EFV/FTC/TDF
Rocket 1 Week 24:
EFV/FTC/TDF
N=159 on
Confirmation
Stable EFV ABC/3TC of Week 12
ABC/3TC + EFV
≥6 months
randomised
TDF/FTC
1:1 + LPV/r
Rocket 2
N=87 on Week 12:
LPV/r ABC/3TC Primary endpoint
+ LPV/r

 Entry criteria
◦ HIV RNA < 50 copies/mL for ≥12 weeks
◦ Total cholesterol at Screening ≥200mg/dL
◦ Baseline CrCl ≥60mL/min
◦ AST and ALT ≤5 x ULN

Moyle G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE0133; Behrens G, et al. ibid. Abst WEPE0110.
n=76 n=74 n=76 n=74 n=75 n=74 n=76 n=74 n=75 n=73
255† 239† 157† 152† 54† 56† 163† 147† 4.80 4.40
P<0.001* P<0.001* P<0.001* P<0.001* P<0.030*

Total LDL HDL TC:


Cholesterol Cholesterol§ Cholesterol Triglycerides HDL Ratio
§ LDL measured directly
† Median value at baseline (mg/dl)
* P-value for between treatment groups comparison is from Wilcoxon Rank Sum test

Moyle G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE0133.
P<0.001 P=0.005 P=0.026 P=0.21 P=0.18

M=E, ITT set


p-values for between treatment comparison are from Wilcoxon Rank-Sum test

Behrens G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE0110.
Creatinine Clearance: Estimated GFR:
Cockcroft Gault (mL/min) - Median (IQR) MDRD (mL/min/1.73 m2) - Median (IQR)
150 150

125 125

mL/min/1.73 m2
100 100
mL/min

75 75

50 TDF/FTC + EFV 50 TDF/FTC+EFV

ABC/3TC + EFV ABC/3TC + EFV


25 25
Normal Range Normal Range

0 0
0 4 12 0 4 12
Weeks Weeks

No participants discontinued due to renal adverse events in either arm

Moyle G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE0133.
ACTG 5142: Impact of Regimen on change
in whole body BMD at week 48 and 96
% Change in BMD

• Factors associated with lower BMI included:


Female, post-menopause, white, lower BMI and higher CD4 cell count
• Significant difference in BMD by NRTI use at week 96 (P<0.001)
• TDF subjects had 1.54% greater declines vs. ZDV (P<0.001)
Huang J, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEAB0304.
5
Change in CrCl (ml/min/1.73m2)

LPV/r or EFV
0
+2NRTIs
EFV + TDF
-5
LPV/r + EFV
-10
LPV/r + TDF

-15

-20

0 24 48 72 96

Time on study (weeks)

Giocoechea M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEAB0305.
Inclusion: Treatment naïve, HIV RNA >5,000 copies/mL
No evidence of primary resistance to NRTIs or NNRTIs by
Genotype or Virtual Phenotype

ETR 400 mg QD Unblinding Follow up


+ 2 NRTIs (n=79)

157 subjects
EFV 600 mg QD
Unblinding Follow up
+ 2 NRTIs (n=78)

6 weeks 48 weeks 2-8 wks 4 wks

 Double-blinded, placebo controlled to Week 48


 Two investigator-selected NRTIs (AZT+3TC; ABC+3TC; TDF+FTC)
 Interim analysis at Week 12 (DSMB review)

Gazzard B, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. LBPE19.
Grade 1 – 4 Treatment Emergent Change in Lipids
Neuropsychiatric Adverse Events Week 12 Change from Baseline
PRIMARY ENDPOINT
All events Drug-related
P<0.001 <0.001
Percent of patients

Mean Change from


Baseline (mmol/L)

Total LDL HDL


(n=79) (n=78) (n=79) (n=78) Cholesterol Cholesterol§ Cholesterol

ETR arm EFV arm


Gazzard B, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. LBPE19.
Randomization Cross-over End
EFV-First ETR-First
On EFV On EFV n=28 n=27
Patients Preference
EFV-first
Patients to choose Prefer EFV 15 1
Stable on EFV,
their preferred drug
without NPS
symptoms
Prefer ETR 6 16
(n=58) No Preference 7 10
ETR-first
On ETR On ETR Drug Prescribed after Trial
EFV 23 12
Baseline Week 6 Week 12
DASS, ESS, GSQS, HIVTSQ DASS, ESS, GSQS, HIVTSQ DASS, ESS, GSQS, HIVTSQ, preference Q ETR 5 15

• At week 12, 16 subjects preferred EFV, 22 ETV and 17 had no preference


• Quality of sleep, depression, anxiety and stress scores did not differ
• No significance difference in safety tolerability or HIV-RNA
• Median TC declined by 0.7mmol/l (29mg/dl) with EFV to ETV switch
(P<0.002)

Nguyen A, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THPE129.
Immediate Switch (IS) Open-Label Phase:
• 2 NRTI + EFV (at least 12 weeks) 2 NRTI Week 12 to Week 24
+ ETR 400mg QD
• 90% IS and 88.9% DS at least + EFV-placebo (n=20) 2 NRTI
1 G2-4 CNS AE from 12 CNS AE 1:1 Randomization To Week 12 + ETR 400mg QD
by ACTG/DAIDS Grade Delayed Switch (DS)
2 NRTI
(N=38) + EFV 600mg QD
+ ETR-placebo (n=18)
 1 LTFU in IS arm, 2 LTFU and 1 SAE in DS arm
 CNS score based on AEs by grade added to sum total
 Baseline to week 12 results (Blinded Phase): IS: G2-4 overall CNS AE (90% to 60%; P=0.041),
abnormal dreams (50% to 20%; P=0.041) DS: No significant changes

Median Number G2-4 CNS AE CNS Score


6 16 P=0.001
5 14
P=0.003 12
4 10
P=0.192
P=0.508
3 8
2 6

1
4 Baseline
2 12 Weeks
0 0
IS DS IS DS
Waters L, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. MOPDB103.
Results of integrated analyses of weekly mean change from baseline in
Numerical Patent Rating score (NPRS)
Change from baseline in NPRS score (%)

* ** *** ** ** *** * * * * **

Study week
* P,0.05
** P<0.01
*** P<0.001a
a Data were compared between treatment groups using a gender-stratified analysis of covariance model with baseline pain score as the covariate
Moyle G, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPE070.
Cause of Death in HIV+ Individuals Initiating ART
(Europe and North America, 1996-2006, n=1597*)

*N=39,272; total deaths=1876.

Antiretroviral Therapy Cohort Collaboration Clin Infect Dis. 2010;50:1387-1396.


 ATLIS: Multi-country, comparative, treatment awareness survey
of 2,035 people living with HIV/AIDS
 Examines global attitudes and perceptions of HIV
HCP-patient communication about co-morbid conditions
% of Total Respondents

Co-Morbid Conditions
Zuniga JM, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLB0104.
Direct Acting Class Select compounds Phase

Telaprevir III
NS3/4A protease Boceprevir III
inhibitors BI 201335 II
MK-7009 II
TMC435 II
R7227 (ITMN-191) II
NS5B polymerase (RdRp) inhibitors
IDX184 II
Nucleos(t)ide analogue PSI-7851 II
INX189 I
ABT-333 II
Non-nucleos(t)ide ANA598 II
MK-3281 II
NS5A inhibitors BMS-790052 II
RG7128 plus RG7227 II
Combinations BI207127 plus BI201335 1b/II
(+RBV)
Thomas D, et al. 18th IAC; Vienna, July 18-23, 2010; FRPL0104.
• Comparison of Fibroscan results and
Are values <19 kPa predictive
endoscopic findings in clinical database in for the absence of varices?
patients with or without esophageal varices
• All patients with liver stiffness measurement
Sensitivity 51%
(LSM) values higher than 12.5 kPa underwent
esophago-gastro-duodenoscopy (n=69) Specificity 94%
PPV 0.96

36 NPV 0.39
Are values >36 kPa predictive
for the presence of varices?
19
Sensitivity 47%
Specificity 75%
PPV 0.38
NPV 0.81

Mausolf M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEPDB0206.
1.0
Retrospective analysis in All Patients Median
 Survival
HIV RNA
22 centers in 7 countries 0.8 <400 c/mL
≥400 c/mL
11.7 mo
4.9 mo
 All HCC cases in HIV+ 0.6
patients from 1995 – 2010 0.4
P=0.007

 Patients were divided into: 0.2


◦ Undetectable: HIV RNA <400
0.0
copies/ml (n=68, 59%)
0 12 24 36 48 60
◦ Detectable: HIV RNA ≥400 Months
copies/ml (n=47, 41%)
Potentially curative therapy
 Conclusions: 1.0 Median
HIV RNA Survival
◦ Undetectable HIV RNA 0.8 <400 c/mL 20.0 mo
associated with better survival ≥400 c/mL 14.6 mo
0.6
◦ Any effective HCC therapy P=0.83
0.4
obliterates the beneficial effect
of suppressed HIV infection on 0.2
survival
0.0
0 12 24 36 48 60
Months

Page E, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUPDB106.
 Data Source: Veterans Affairs’ Clinical Case Registry
 Predictors:
◦ HCV co-infection: HCV or HCV antibody(+)
◦ Chronic kidney disease: Estimated GFR<60 by MDRD
◦ Other: BMI, Age, Race, ARV exposure, Smoking
 Outcomes:
◦ Osteoporotic fractures: Vertebral fractures, Hip fractures,
and Wrist fractures
◦ All-cause mortality
 Patients: 56,660 included in the analysis; 98.1% male;
31.2% HCV+; 45 years mean age at entry
 Follow-up: 305,237 patient-years; mean: 5.4 yrs/pat.
(range: 0 – 23.8 yrs)
Bedimo R, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUAB0104.
• 948 individual patients sustained at least one osteoporotic fracture
(106 vertebral, 451 wrist and 308 hip)
• Rate/1000 patient-years: HIV 2.54 vs. HIV/HCV 3.25 Vertebral
8 Hip
Fracture Rate (per 1,000 patient-years)

Wrist
7
Total
6
General Population
5

0
18-29 30-39 40-49 50-59 60-69 ≥70
Age at Diagnosis (Years)
Bedimo R, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUAB0104.
Factors Hazard Ratio (95% Confidence Interval; P value)

  Univariate Analysis Multi-variable Analysis

HCV Co-infection 1.27 (1.11 - 1.44; P=0.0003) 1.43 (1.22 - 1.69; P<0.0001)

CKD (eGFR <60) 1.34 (1.03 – 1.74; P=0.03) 1.10 (0.77 – 1.58; P=0.61)

White Race 1.64 (1.41 – 1.89; P<0.0001) 1.75 (1.49 – 2.04; P<0.0001)

Age (per 10 year 1.49 (1.40 – 1.59; P<0.0001) 1.50 (1.38 – 1.63; P<0.0001)
increase)
ART Use 0.57 (0.48 – 0.67; P<0.0001) 0.44 (0.35 – 0.56; P<0.0001)

Tobacco Use 1.30 (1.14 – 1.48; P<0.0001) 1.48 (1.26 – 1.75; P<0.0001)

Diabetes 1.18 (1.02 – 1.37; P=0.02) 1.02 (0.85 – 1.22; P=0.85)

BMI <20 1.54 (1.29 – 1.82; P<0.0001) 1.40 (1.13 – 1.73; P=0.002)

Bedimo R, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. TUAB0104.
 Estimate of the total number of cancers (cancer burden) in patients with
AIDS as well as in HIV(+) patients without AIDS in the US
 CDC collects HIV data from US states
◦ AIDS from entire country from 1991-2005
◦ HIV only from 34 states 2004-2007
 NCI HIV/AIDS cancer match study
AIDS-defining Cancers in People with AIDS in the U.S. 7000
8000
7000 6000

6000 5000
5000
4000
4000
3000
3000

2000 2000

1000 1000

0 0

■ 0-12 yrs ■ 13-19 ■ 20-29 ■ 30-39 ■ 40-49 ■ 50-59 ■ 60+ yrs


yrs yrs yrs yrs yrs
Shiels M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEAB0101.
Non-AIDS-defining Cancers in People
with AIDS in the U.S.

2500 700
2250
600
2000
1750 500 2191
1500
400
1250
1000 300
750
200 7869
500
100 5327
250
0 0

■ 0-12 yrs ■ 13-19 ■ 20-29 453


■ 30-39 ■
yrs 40-49 ■ 50-59
yrs ■ 60+ yrs Data for 34 U.S. States (2004-2007)
yrs yrs yrs

Shiels M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEAB0101.
Ass Wr WB