HIV management in Australia – Part 2 + extended learning activity

Case scenario

Trang started antiretroviral therapy in 2010. Initially she was prescribed tenofovir disoproxil fumarate + emtricitabine (combination tablet) plus dolutegravir. A few years ago her doctor changed her to Biktarvy (tenofovir alafenamide + emtricitabine + bictegravir) to reduce the pill burden. She has always been virologically suppressed and takes no other medicines. Today she presents you with a new prescription for Dovato (dolutegravir + lamivudine). She explains that she has been doing some reading with her doctor and they found switching to dual therapy is approved as a safe option for suppressed patients with no prior resistance.

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Introduction

Human immunodeficiency virus (HIV) treatment and prevention strategies have come a long way over the past few decades. With the advent of highly active combination therapy and well-tolerated antiretroviral therapy (ART) regimens, people living with HIV (PLHIV) who are diagnosed early and commence ART promptly now have a life expectancy closer to the general population.¹ However, comorbidities (including chronic liver, kidney or lung disease, some cancers, diabetes and cardiovascular disease [CVD]) occur at earlier ages compared to the non-HIV population.¹ Also, the HIV-positive population in Australia is ageing. In 1986, approximately 5% of PLHIV in Australia were over 50 years of age.² By 2017, this had increased to 46%.² 

ART should be started as soon as practicable after diagnosis and continue throughout life. The choice of ART regimen is tailored to the individual patient, and takes into consideration baseline HIV resistance test results, comorbidities and lifestyle factors that may affect adherence, which is essential for treatment to be successful. Sometimes it is necessary to switch ART. This generally occurs in the context of an adverse effect, medicine toxicity, pregnancy or a new comorbidity requiring an interacting medication.

Pharmacists are able to assist older PLHIV with medication management, polypharmacy, drug–drug interactions and drug–disease interactions.^3–6 In addition, pharmacists have a role to play in assisting younger PLHIV with complexities including pregnancy, coinfection with hepatitis B or C, mental health diagnoses and substance misuse. 

This article outlines the management of complex patients initiating or switching antiretroviral therapy.

Comorbidities

Comorbidities in PLHIV can be challenging to manage. This is particularly the case in older PLHIV taking complex antiretroviral regimens which are associated with many drug interactions. In addition, older PLHIV can have fewer simplifying switch options due to past treatment failures and resistance. When determining the most appropriate ART for patients with comorbidities, drug–disease interactions, drug–drug interactions and the overall increased pill burden need to be considered. 

Treatment-experienced PLHIV may have a resistant virus and require more complex regimens, such as a boosted protease inhibitor, which can interact with their disease or concurrent medications.  

Key considerations that need to be made when determining the most appropriate ART for patients with comorbidities are outlined in Table 1. This list is not exhaustive, and pharmacists should always check tertiary references for information on doses, adverse effects and other important prescribing considerations.

While Table 1 provides a guide to key considerations when determining the most appropriate ART for patients with comorbidities, there are many caveats. For example, some PLHIV have extensive ART resistance and may be unable to avoid all drug–disease interactions. In this situation, clinicians weigh up the risks and benefits, taking into consideration current available evidence. For PLHIV with comorbidities, pharmacists can provide advice on interactions with concurrent medications and dose adjustments. They can also assist with monitoring of comorbidities (for example, blood pressure or blood glucose levels). 

Table 1 – Comorbidity considerations when choosing antiretroviral therapy 

References: Panel on Antiretroviral Guidelines for Adults and Adolescents,⁷ European AIDS Clinical Society,⁸ The Alfred,⁹ Yombi,¹⁰ Brown,¹¹ Rossi,¹² Saberi,¹³ Panel on Antiretroviral Guidelines for Adults and Adolescents,¹⁴ PSA¹⁵

A study in the Netherlands, published in 2017, found that lifestyle modifications such as smoking cessation and controlling hypertension and hyperlipidaemia had a more profound effect on a patient’s ongoing CVD risk compared to avoiding protease inhibitors and abacavir.¹⁶ Of note, the prevalence of smokers among Australian PLHIV is estimated to be around 30%, which is double that of the general population.¹⁷ Pharmacists in both the community and hospital setting are well placed to continue to encourage and support quit attempts. 

For many younger patients seen in community pharmacies, ART may be their only regular medications. Even in the absence of comorbidities, it is important to consider any non-prescription or complementary medicines they may be taking, as these can be implicated in significant interactions with antiretrovirals. For example, products containing iron, magnesium, calcium or zinc must be separated from integrase inhibitors to avoid a pharmacokinetic interaction in the gut.¹⁸ Additionally, non-prescription mometasone or fluticasone nasal products should be avoided with boosted-ART due to the risk of Cushing’s syndrome.¹⁸ ART drug interactions were covered in the first article in this series, ‘HIV Management in Australia: Part 1’, published in the December/January edition of Australian Pharmacist.

Coinfections

Hepatitis C

Prior to Pharmaceutical Benefits Scheme (PBS) availability of direct-acting antiviral (DAA) therapy for hepatitis C (HCV) in 2016, it was estimated around 12% of Australian PLHIV also had HCV.¹⁹ With the availability of DAA, this figure has reduced.^20,21 

PLHIV with HCV coinfection have a more rapid progression to HCV-related liver disease and higher risk of progression to cirrhosis.²¹ All PLHIV should be screened for HCV, and if at high risk, screening should be repeated annually.²¹ Once cured of HCV, if a patient is reinfected, they can be offered PBS-subsidised retreatment as per clinical guidelines and PBS criteria. It is important to check for drug interactions with HCV treatments. The University of Liverpool’s HIV Drug Interaction Checker (available at www.hep-druginteractions.org/checker) is a useful online reference. 

Hepatitis B

In addition to HCV, it is important to include hepatitis B (HBV) screening serology for patients newly diagnosed with HIV. HIV and HBV infections may occur together due to their shared modes of transmission (sexual contact, sharing injection equipment, mother to child).²² 

The prevalence of HBV and HIV coinfection in Australia is approximately 5%.²² HBV disease progression to chronic infection and cirrhosis is more common in those with HIV/HBV coinfection, compared to those with HBV monoinfection.¹⁸ Progression of HBV increases the liver-related mortality rate.^22,23

If screening serology shows the PLHIV does not have HBV, or immunity to HBV, vaccination should be offered. If the serological tests show evidence of HBV infection, the selected ART regimen should contain tenofovir, plus emtricitabine or lamivudine.^7,22 These antiretrovirals have activity against both HIV and HBV. When tenofovir isn’t suitable, entecavir, a HBV-active medicine, may be used, along with fully active ART.^7,22 HBV DNA viral load should be monitored regularly to ensure it remains suppressed. 

If ART needs to be modified for treatment failure or for simplification, it is important to continue or change to medicines with anti-HBV activity. Stopping HBV active medicines can cause serious hepatocellular damage resulting from the reactivation of HBV.²⁴

Tuberculosis

Although Australia has a low burden of tuberculosis (TB), it remains a global health crisis, with an estimated 10 million new cases in 2019.²⁵ Of all TB cases at this time, 8.2% were also living with HIV.²⁵

The main consideration when treating patients with HIV/TB coinfection is drug interactions with anti-TB medicines, particularly rifampicin. Rifampicin is a strong UGT1A1, CYP450 enzyme and p-glycoprotein inducer, so ART choice requires careful consideration.²⁶ Some antiretrovirals are contraindicated with rifampicin due to suboptimal levels, including tenofovir alafenamide and bictegravir.²⁶ Other antiretrovirals require dose modification when taken with rifampicin (for example, the dose interval for dolutegravir needs to be increased to twice daily).²⁶

Once the treatment course for TB is complete, ART can be adjusted as required.

Pregnancy and HIV

In Australia, routine HIV testing occurs in early antenatal care. This enables early diagnosis of HIV, adequate time to implement measures to reduce the risk of mother-to-child transmission, and the opportunity for the woman to be offered treatment and psychological support.²⁷

All women with HIV should receive ART early in pregnancy for their own health and for the prevention of perinatal HIV transmission. Infectious disease physicians, and pharmacists who specialise in infections in pregnancy, manage HIV in pregnant women, working together with obstetricians and a paediatric team. Recommendations on specific antiretroviral agents in pregnancy (and pregnancy planning) are regularly updated as new data emerges. One useful resource is the US Department of Health and Human Services’ Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States.²⁸ Data is limited for some newer agents, such as bictegravir, where pregnancy-specific pharmacokinetics and safety have not yet been established. Cobicistat is generally not recommended due to altered pharmacokinetics in later pregnancy resulting in lower levels of both cobicistat and the antiretroviral it is boosting.²⁸

There are four strategies to reduce the transmission of HIV from mother to child:

• Suppress maternal viral load (VL) with ART that is safe in pregnancy (extra adherence support may be required).
• An appropriate mode of birth based on maternal viral load at 36 weeks, decided after discussion between the obstetric team and patient.
• A considered approach to breastfeeding versus formula feeding that takes into account the risk of the infant acquiring HIV through breastfeeding, maternal viral load, and maternal and infant compliance with ART. Formula feeding is still recommended as the safest choice with the current available evidence; however, Australian resources are now available to help women to make an informed decision and work with healthcare providers to minimise risk.²⁹
• Prophylactic ART for newborn and follow-up care with a paediatric infectious disease physician.²⁸  

Switching antiretroviral therapy

Advances in ART have made it possible to switch a patient’s ART in some situations.

Any decision to switch ART should be carefully considered, taking into account past treatments, regimen failures and resistance genotype results. The patient’s concurrent medications and comorbidities (for example, coinfection with HBV) must also be considered. 

In virologically suppressed patients, there are a number of reasons for a regimen switch, including:

• reducing pill burden
• reducing treatment cost (fewer PBS co-payments if fewer tablets)
• avoiding drug interactions
• pregnancy (switch to a regimen that is safe in pregnancy)
• change in comorbidities or coinfections. 

Switching a patient who is failing ART (viral load >200 copies/mL on consecutive tests) is complex; specialist advice is recommended. 

There are several potential causes for virological failure. These can be patient related, virus related or regimen related. To guide any new regimen choice, a resistance genotype is taken while the patient is taking the current failing regimen. This, together with the treatment history, previous genotype results and consideration of patient factors, will assist in choosing a new regimen that the virus is susceptible to. This is a complex process; further information is available on the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine website (https://arv.ashm.org.au/virologic-failure).

Whether switching for regimen optimisation, simplification or failure, consideration of new drug interactions and removal of previous interactions are important roles of the pharmacist.

Knowledge to practice

HIV is a chronic treatable condition, usually requiring lifelong ART that is available through community pharmacies. This provides pharmacists with regular contact with PLHIV and the opportunity to contribute to optimal management of their condition through medication optimisation and lifestyle advice. 

Adherence to ART is paramount to enabling its success, including achieving virological suppression, minimising immune function effects, avoiding drug resistance, and preventing opportunistic infections and transmission.³⁰ Pharmacists are able to provide education on the importance of adherence, identify possible adherence issues and provide advice on strategies to aid adherence to ART. This includes liaising with the patient’s prescriber where potential adherence issues are identified, to determine the suitability of switching ART to avoid side effects, reduce pill burden or reduce the cost of treatment.

Comorbidities are an important consideration when determining the most appropriate ART. Pharmacists can advise on potential drug interactions with concurrent medicines, including non-prescription medicines, and drug–disease interactions, such as abacavir and cardiovascular disease. Advice about lifestyle modification, including smoking cessation, regular exercise and healthy eating, can help to reduce the patient’s cardiovascular risk and improve overall physical health. 

Along with comorbidities, pharmacists should consider any coinfections and whether the patient’s ART provides adequate cover (in the case of HBV), that the coinfection is being appropriately treated (if required) and that there are no drug interactions. 

Conclusion 

As the population of PLHIV ages, management of comorbidities and polypharmacy will become more complex. Although some of the complexities will be managed by teams of infectious disease physicians and specialist HIV pharmacists, community pharmacists also have a role to play. As health professionals who see PLHIV at each dispensing of their regular medication, pharmacists are able to contribute to their optimal management through the provision of both medicine and lifestyle advice as well as vaccination services. 

Key points:

• Comorbidities and coinfections should always be considered when dispensing ART, as they are associated with a number of drug–disease and drug–drug interactions. 
• Lifestyle interventions, including smoking cessation, are particularly important for people living with HIV (PLHIV) with comorbidities and other cardiovascular risk factors.  
• Antiretroviral therapy (ART) should be provided to PLHIV who are pregnant for their own health and to reduce the risk of perinatal transmission. Recommendations on ART in pregnancy are regularly updated as new data is obtained.
• When switching ART, drug interaction implications should be considered, including the effect of drug interactions from the old regimen no longer occurring and any potential interactions with the new regimen.

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ALISON DUNCAN BPharm, GradDipClinPharm, MSHP is a Senior Clinical Pharmacist and Team Leader working at the Alfred Hospital and Melbourne Sexual Health Centre. She has a passionate interest in infectious diseases.

KATE MACKIE BPharm, GradDipClinPharm, MSHP, BCGP is a Senior Clinical Pharmacist at Alfred Health, Melbourne Health and Barwon Health. 

STAV MANTAS BPharm (Hons), MSHP is a Senior Clinical Pharmacist at Monash Health with 15 years’ experience in the HIV setting. She set up the HIV outpatient pharmacy service and is an integral member of the multidisciplinary team. 

Conflict of interest 

Alfred Health received funding from Gilead Sciences and ASHM (with support from ViiV Healthcare) to lead the Pharmacist Review of Medications for People Living with HIV seen in General Practice (PROM-GP) study.

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