HIV Treatment Adherence and the PARTNER study Janey

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 CD 4 cells and HIV Viral load in the absence of HIV treatment Source: HIV i-base http: //i-base. info/ttfa/section-2/214 -how-cd 4 -and-viral-load-are-related/

Effect of HIV treatment on CD 4 count and viral load Source: HIV i-base http: //i-base. info/ttfa/section-2/214 -how-cd 4 -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 • • • Highly Active Anti. Retroviral Therapy (HAART) Antiretrovirals (ARV’s) Antiretroviral Therapy (ART) Combination Anti. Retorviral Therapy (c. ART) 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 CD 4 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%20 EN 7. 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 • So…when to start?

When to start ART? • ART is always recommended if the CD 4 cell count is <350 cells/m. L • 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 CD 4 cell count is <500 cells/m. L • HCV if the CD 4 cell count is <500 cells/m. L • HBV if the CD 4 cell count is >500 cells/m. L 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 CD 4 • Reduces HIV transmission • Prevents transmission of drug resistant strains of HIV

Adherence associated Factors • Personal commitment • Lifestyle and work • • • 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 • • • Lack of understanding Younger age Psychosocial issues Nondisclosure of HIV serostatus Substance abuse Stigma

Consequences of poor adherence • • • Incomplete viral suppression Continued destruction of immune system Disease progression Emergence of resistant strains Limited future options

Nursing Role in ongoing adherence • • • 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; >5 xday, >5 days, 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 • • 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: • • • 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 (CD 4/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 (CD 4/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 1 st 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 estimated rate/risk 95% confidence interval

Rate of HIV transmission according to sexual behaviour reported by the negative partner

Conclusions • Interim results after 894 eligible CYFU report an overall HIV transmission rate of zero through condomless sex with a plasma VL < 200 copies/m. L 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 PARTNER 2 (2014 -2017) will provide more precise estimates for transmission risk to inform policy and also individual choice on condom use