Transcript HIV Treatment, Adherence and the PARTNER study

HIV Treatment,
Adherence and
the PARTNER
study
Janey Sewell
Research Nurse
Aims of the session:
• HIV treatment :
• Aim of treatment?
• How does it work?
• When to start?
• Adherence:
• Why is it important?
• What is the nursing role?
• How to manage side effects?
• PARTNER study: Treatment as Prevention
Aim/goals of HIV therapy
• The primary goal is to prevent HIV-related morbidity
and mortality
• Suppress HIV viral load to undetectable
• Restore and/or preserve immunologic function
• Prevent HIV transmission
Tx is lifelong – need to decide the right time to start
Natural progression of CD4 cells and HIV Viral load in the
absence of HIV treatment
Source: HIV i-base
http://i-base.info/ttfa/section-2/214-how-cd4-and-viral-load-are-related/
Effect of HIV treatment on CD4 count and viral load
Source: HIV i-base
http://i-base.info/ttfa/section-2/214-how-cd4-and-viral-load-are-related/
HIV treatment – how does it work?
• HIV – difficult to treat
• Resistance can develop if drugs are not strong enough
or if does are missed
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Highly Active AntiRetroviral Therapy (HAART)
Antiretrovirals (ARV’s)
Antiretroviral Therapy (ART)
Combination AntiRetorviral Therapy (cART)
Anti HIV drugs
BUT HOW DO THEY WORK?!
This works because there are
3 different types of drug
actively fighting the virus
How do HIV drugs work?
HIV reproduces in the CD4 cells through a series of stages
HIV drugs work by interfering with these stages
Fusion /Entry Inhibitors
Stop HIV getting in to
the cell
Nukes and non nukes
Stop one of the main
ways HIV reproduces
inside the cell
Integrase Inhibitors Stop
HIV being integrated in
to the cells genetic
material
Protease Inhibitors
Stop new HIV being
cut into smaller
proteins
How do HIV drugs work?
• None of the current drugs are strong
enough to fight HIV on their own
• Using 3 or more drugs together to
treat HIV suppresses the virus to very
low levels and reduces the risk of
resistance
• Most guidelines including EACS
recommend first line treatment is a
combination of:
2 nukes combined with EITHER a non-nuke OR
a PI (preferably a PI boosted with ritonavir)
1 European AIDS Clinical Society (EACS) 2014
http://eacsociety.org/Portals/0/140601_EACS%20EN7.02.pdf
Problems with ART
• There are reservoir sites for HIV
• ART cannot penetrate into some areas
• We cannot eradicate the virus completely -->
weigh up health benefits with commencing life
long treatment
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So…when to start?
When to start ART?
• ART is always recommended if the CD4 cell count is
<350 cells/mL
• AIDs diagnosis
• HIV related co-morbidity i.e. HIV associated kidney
disease or HIV associated neurocognitive impairment
• Non-AIDS-defining malignancies requiring
immunosuppressive radiotherapy or chemotherapy
When to start ART
Co-infection
• HBV if the CD4 cell count is <500 cells/mL
• HCV if the CD4 cell count is <500 cells/mL
• HBV if the CD4 cell count is >500 cells/mL and
treatment of hepatitis B is indicated
When to start ART
• Patients presenting with AIDS or a major
infection
• Treatment of primary HIV infection
• Treatment to reduce transmission
Adherence vs Compliance
Adherence: the act or quality of sticking to
something, steady devotion; act of adhering
– Acceptance of an active role in one’s own
health care
Compliance: The act of conforming, or
yielding
– Lack of sharing in the decision made between
provider and client
Adherence – what to consider?
• Ready for treatment?
• Discuss:
- goals and demands of treatment
- potential side effects
- dosing schedule
- strategies for coping
Adherence
Must take 95% of the doses
• Adherence is the second strongest
predictor of progression to AIDS/death,
after CD4
• Reduces HIV transmission
• Prevents transmission of drug resistant
strains of HIV
Adherence associated Factors
• Personal commitment
• Lifestyle and work
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Difficulty with taking medication
Complex regimens and adverse drug effects
Co-infection – complex drug regimens
Cost issues
Support from partner, family, friends
Adherence associated Factors
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Lack of understanding
Younger age
Psychosocial issues
Nondisclosure of HIV serostatus
Substance abuse
Stigma
Consequences of poor adherence
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Incomplete viral suppression
Continued destruction of immune system
Disease progression
Emergence of resistant strains
Limited future options
Nursing Role in ongoing adherence
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Acknowledge you understand it’s difficult
Confirm understanding of their regimen
Assess adherence
Find out reasons for missed doses
Ask about side effects
Offer suggestions to overcome obstacles
Multidisciplinary approach
Same message from all
Doctors
Nurses
Adherence
message for
the patient
Pharmacist
Counsellor
ART resistance
• Resistance occurs with poor adherence
• Mutations during replication of the virus can
allow to multiply while on ART
• Resistant drugs lead to viral load failure
• Resistance testing
ART resistance
Side effects
Common:
• GI gastrointestinal : nausea, vomiting,
diarrhoea, abdo pain
• CNS Central nervous system: headache,
dizziness, fatigue, insomnia, vivid dreams,
depression, anxiety
• Skin: Jaundice, rash
Side effects
Efavirenz: CNS effects,
sleep disturbance, abnormal dreams, rash
Atazanavir: Jaundice, increased bilirubin
Abacavir: Hypersensitivity reaction
Nevirapine: Stevens Johnson syndrome, liver
toxicity
Kaletra: Diarrhoea
Managing side effects
Diarrhoea
• Anti-diarrhoea medications (loperamide)
• Avoid spicy foods
• White rice, white pasta, pulses, bananas
• Continue to eat and drink
• If severe contact Dr; >5xday, >5days, weight
loss, blood/fever/mucous
Managing side effects
Nausea/Vomiting
• Anti nausea drugs
• Small frequent meals, bland foods
• Dry or salty foods, crackers, dry toast
• Herbal tea or root ginger
• Sips fluids
• Refer to Dr: dehydrated/unable to drink,
fever, abd pain
Managing side effects
Headache
• Paracetomal
• Avoid caffeine
• Rest, quiet, dark
• Refer to Dr: frequent and severe, blurred
vision, altered consciousness
Managing side effects
CNS effects
• Inform Dr especially if depression etc
• Take medication at night
• Avoid alcohol or drugs
• Seek counselling
• If does not lessen or not tolerated may
switch
Managing side effects
Rash
• Use mild soaps, Tepid baths
• Keep hydrated
• Inform Dr
• Check for additional effects
• Are they on ABC EFV or NVP
• May treat through with antihistamines
Managing side effects
Fatigue
• Get enough sleep
• Good balanced diet
• Avoid alcohol tobacco or drugs
• Regular exercise
• Inform Dr
Long term side effects
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Kidney problems
Metabolic changes
Heart disease
Liver problems
Lipodystrophy
Peripheral neuropathy
Bone
The PARTNER study
•The PARTNER study is an observational
multi-centre study of HIV serodifferent
couples in which the positive partner is
on ART, taking place in 75 European
sites with 20 sites in the UK
Aim
•To evaluate the risk of within-couple
HIV transmission (HT and MSM) during
periods where condoms are not used
consistently and the HIV positive
partner is on suppressive ART
Background
• Rakai study, Swiss cohort, HPTN 052 results:
Serodifferent heterosexual couples with no STI’s
Viral load =
reduced HIV transmission
by up to 96%
• BUT: taking all studies in serodifferent couples to date,
condomless sex is reported for only 3301 cumulative
couple-years of follow up (CYFU)
The PARTNER study is the first to look at the risk of
HIV transmission in the absence of condoms
HOW:
• Enrols couples who report unprotected sexual intercourse (in
the last 4 weeks) and may do so again in the future
Baseline visit:
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Informed consent with reference to positive partner’s HIV status transmission risk
Consistent condom use is the most effective way to prevent
transmission
Self completed confidential questionnaire for both partners
HIV test for the –ve partner
Recording of clinical data of +ve partner (CD4/VL/ART)
Follow-up visit:
• 4-6 monthly self completed confidential risk behaviour
questionnaire
• HIV test for the –ve partner
• Recording of clinical data of +ve partner (CD4/VL/ART)
• Re-consented after 2 years of study participation
If, during the course of the study, the -ve partner has a
positive HIV test result, blood samples are obtained from
both partners for delinked anonymised viral sequencing
Study has been running since March 2011 and is planned to
run until 2017
Interim analysis
• CROI 2014 : Overall 1,110 couples were recruited by
1st Nov 2013
• 767 couples contributed 894 eligible Couple Years of
Follow Up (CYFU)
586 in heterosexuals
308 in men who
have sex with
men (MSM)
Rate of HIV transmission according to sexual
behaviour reported by the negative partner
Rate of within couple
transmission (per 100 CYFU)
0
0.2 0.4 0.6 0.8
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1.2
10 year risk (%) of within
couple transmission
0
Any sex
(CYFU=894)
Anal sex
(CYFU=374)
estimated rate/risk
95% confidence interval
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4
6
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10
Rate of HIV transmission according to sexual behaviour
reported by the negative partner
Rate of within couple transmission
(per 100 CYFU)
0
HT
Vaginal sex with ejaculation (CYFU=192)
HT
Vaginal sex (CYFU=272)
Receptive anal sex with ejaculation
(CYFU=93)
MSM Receptive anal sex without ejaculation
(CYFU=157)
Insertive anal sex (CYFU=262)
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Conclusions
• Interim results after 894 eligible CYFU report an overall HIV
transmission rate of zero through condomless sex with a plasma
VL < 200 copies/mL on ART, despite a significant number of
sexual acts.
• Uncertainty over the upper limit of risk remains, particularly over
receptive anal sex with ejaculation
• Additional follow-up in MSM through PARTNER2 (2014-2017) will
provide more precise estimates for transmission risk to inform
policy and also individual choice on condom use