General practitioners and HIV

David Baker: East Sydney Doctors, Sydney, NSW
Louise Owens: Sexual health physician, Director of state-wide sexual health service, Tasmania

The purpose of this chapter is to review the role of the general practitioner (GP) in providing care for people living with HIV infection. This chapter is based on previously published reviews for GPs as well as relevant guidelines.[1][2]

GPs have a vital role in diagnosing HIV infection through appropriate testing. Increasingly, GPs also have a role in preventing human immunodeficiency virus (HIV) infection through well known forms of biomedical prevention by encouraging condom use and advising new interventions such as pre-exposure prophylaxis (PrEP).

The success of antiretroviral therapy (ART) has transformed HIV infection into a manageable chronic disease. The life expectancy for patients newly diagnosed with HIV infection in the developed world now approaches that of the general population provided they receive regular care. [3] For most people this care will mean life-long daily medication with a combination of antiretroviral drugs.

Recent results from large clinical trials support the added health benefits of treating all people living with HIV from the time of diagnosis.[4] Early treatment has been shown to improve the long-term health of people with HIV. This approach has also been shown to reduce HIV transmission to others . The use of ART for prevention purposes is known as ‘Treatment as Prevention’ (TasP).

Although most GPs will rarely see a person with HIV, they have an important role in regular HIV testing of at-risk patients and in considering HIV testing in patients presenting with possible clinical signs of HIV infection. The testing section will discuss some of the key issues around appropriate screening for HIV.

As patients with HIV are living longer, often into old age, their health needs are similar to those of an ageing population. They will need comprehensive primary health care which generally follows standard guidelines. Recommended preventive activities for HIV patients are discussed in the HIV management section. Management of comorbidities will also be discussed in this section.

HIV care may be provided by the patient’s GP or by an HIV specialist under a shared care model. Later sections will discuss some of the major issues in primary care HIV management and also the complexities of shared care management.

People living with HIV are a diverse range of Australians who have differing health needs and backgrounds. Some of the complexity of these populations will be discussed in the section on providing care for diverse populations.

Background to HIV in Australia

Who has HIV in Australia?

Over 27,000 people are thought to be living with HIV in Australia, with 1081 new infections diagnosed in 2014.[5] A large majority (87%) of HIV diagnoses in 2014 was among males. The median age at HIV diagnosis has remained stable and was 37 years in 2013 with most infections occurring among men who have sex with men. The number of new infections has been steadily increasing since 1999 but now seems to have stabilised (Figure 1). An estimated 3350 of all HIV cases in Australia are undiagnosed.

Figure 1. Newly diagnosed HIV infections in Australia, 1984 – 2014[6]

gp hiv fig1

 

Source: The Kirby Institute. Annual Surveillance Report 2015.[7]

Many patients who acquired HIV infection in the 1980s have survived and are now ageing and presenting with increasing comorbidities that require comprehensive care from a range of practitioners.

What are the major causes of mortality?

With improved treatment fewer patients living with HIV are progressing to acquired immune deficiency syndrome (AIDS). Increasing proportions of HIV patients are experiencing other health problems associated with ageing, including malignancies and cardiovascular disease. Given the high prevalence of co-infection with hepatitis B and C viruses, there is ongoing morbidity and mortality from chronic liver disease. The changing nature of mortality in a large cohort of people living with HIV in Australia and Europe is shown in Figure 2.[8]

Figure 2. Changing causes of death in HIV infection over time (the D:A:D cohort) AIDS: acquired immune deficiency syndrome; CVD: cardiovascular disease; HIV: human immunodeficiency virus; NADM: non-AIDS defining malignancy 

gps fig2

How well does Australia provide HIV treatment?

Compared with other developed countries Australia has high rates of HIV diagnosis and treatment of most people living with HIV.[9] However there are a number of areas in the HIV cascade of care that can be enhanced that will result in better health outcomes. GPs have important roles to play in all steps of the cascade particularly in early diagnosis and support of patients to remain in long-term care.

Figure 3. The 2014 HIV diagnosis and care cascade Source: The Kirby Institute. Annual Surveillance Report 2015.[10]

gps fig3

Who cares for people with HIV?

About half of all people living with HIV in Australia are managed predominately by GPs with experience and additional training in HIV infection and the other half are managed in immunology or infectious disease clinics or sexual health clinics.[11] A chronic disease model is appropriate for the care of people living with HIV and this approach fits well within a general practice setting.

HIV testing

Early diagnosis of HIV infection is important so that patients can be offered timely monitoring and treatment to prevent immune suppression and resulting complications. Other benefits of early diagnosis include timely contact tracing and counselling to reduce transmission. About 20% of patients in Australia continue to be diagnosed late, with a CD4 T-lymphocyte (CD4) count below 200 cells/L (normal range, 500 to 1500 cells/L), which indicates severe immune deficiency.[12] CD4 lymphocytes are the major component of the immune system damaged by HIV infection.

Natural history of HIV infection

About 70% of patients will have a primary HIV or seroconversion illness within 1 to 6 weeks after infection. This illness, which usually lasts about 4 to 14 days, can resemble glandular fever or rubella but it can also be very non specific. HIV infection should be considered in any patient as part of the differential diagnosis for febrile or presumed viral infections, particularly in people from at-risk groups such as men who have sex with men or immigrants from or visitors to high prevalence countries.

Following the primary illness, most people will enter a relatively asymptomatic phase lasting for several years. Over time, mild then more severe immune compromise will develop. This may be marked by the presence of conditions such as oral thrush, diarrhoea, weight loss, recurrent respiratory infections and skin conditions, including shingles, seborrhoeic dermatitis and folliculitis.[13] CD4 lymphocyte counts will generally drop by about 60 to 80 cells/μL per year from an average normal level of approximately 800 cells/μL to below the normal lower limit of 500 cells/μL Below 200 cells/μL patients will become increasing vulnerable to AIDS-defining conditions such as Pneumocystis jiroveci pneumonia (PJP, previously called Pneumocystis carinii pneumonia, or PCP). The various stages of HIV infection are shown in Figure 4.[14]

Figure 4. The natural history of HIV infection[15] CMV: cytomegalovirus; HIV: human immunodeficiency virus; KS: Kaposi sarcoma; MAC: Mycobacterium avium complex; NHL: non-Hodgkin lymphoma; PJP: Pneumocystis jirovecii pneumonia

gps fig4

HIV testing

Testing for HIV infection should be performed after appropriate informed consent has been obtained. Current fourth generation combined antibody/antigen tests (HIV antibody and HIV p24 antigen) are very sensitive and specific but must always be followed with a confirmatory reference test if they are positive.[16] Additional testing should be ordered if there is concern about possible primary HIV illness – the local pathology laboratory should be consulted.

The window period for HIV testing is officially stated to be 3 months from the time of exposure but most patients will have a positive antibody/antigen test by 6 weeks after infection. Making a new diagnosis of HIV can be a very distressing time for the patient as well as for his or her treating doctor. Expert advice following a new HIV diagnosis can be obtained online as well as by phone from local specialist clinics or from the Australasian Society for HIV Medicine (ASHM) (http://www.ashm.org.au). Despite treatment advances and changes in social perceptions, HIV infection remains a stigmatised condition, and all people who are tested should be engaged in appropriate and sensitive discussions in terms of giving informed consent for HIV testing and how their test results will be given

Indeterminate results

Occasionally, an equivocal or indeterminate result from HIV testing may occur. This result can be a source of great anxiety for the patient. Advice in interpreting indeterminate results should always be sought from specialist HIV clinicians based in hospitals or public sexual health clinics or from pathology laboratory staff. In the case of HIV antibody testing, a positive ELISA and a single band on Western blot constitutes an indeterminate result.

A patient with an indeterminate result who has reported a recent high-risk exposure is regarded as being in the window period of infection and may require considerable support during this time to deal with anxiety. Further tests for viral antigens may be indicated to test for the presence of infection and should only be performed in consultation with a specialist clinician. In populations of low seroprevalence of bloodborne viral infections, indeterminate results may be false positives. Factors such as pregnancy, past blood transfusions, intercurrent viral infections, autoimmune diseases and malignancies may play a role in indeterminate results. Upon re-testing at approximately 2 weeks, a second indeterminate result where there are no new bands on the HIV Western blot is regarded as confirmation of negative status. However, to be absolutely sure and to address the fears of the person being tested or the health-care worker’s doubts, HIV testing at approximately 12 weeks post-exposure should be performed.

For the latest guidance on HIV testing please see the National HIV Testing Policy available at http://testingportal.ashm.org.au/hiv.[17] HIV and sexually transmissible infections (STI) testing should be incorporated into regular health checks for all those at risk but especially for those in higher-risk groups (Table 1). These risk groups include men who have sex with men who are advised to have screening at least once a year and up to four times a year depending on behavioural risk assessment.[18]

Patients who request testing may not reveal their true level of risk. In some situations, the clinician may assess the risk of infection as low, but the patient’s actual risk of infection may be high. For this reason, all patients requesting testing should be tested.

Table 1. Indications for HIV testing
  • Clinical suspicion of HIV infection
    • an opportunistic infection (including tuberculosis)
    • HIV-linked malignancy
    • symptoms and signs consistent with primary HIV infection (e.g. mononucleosis-like syndrome)
    • inclusion of HIV within the differential diagnosis
  • Diagnosis of a condition with shared transmission route:
    • sexually transmitted infection (STI)
    • hepatitis B or C
  • Reported high-risk exposure
  • Unprotected sexual intercourse with a partner whose HIV status is unknown
  • Reported reuse of equipment used for skin penetration
  • In the setting of contact tracing
  • Epidemiological considerations or the opportunity to prevent vertical transmission
    • gay men and other men who have sex with men
    • people who inject drugs
    • people with multiple sex partners/recent partner change
    • people having travelled to countries of high prevalence and engaged in risk behaviour
    • people from high-prevalence countries
    • partners of the above
    • partners of HIV +ve
    • pregnant women
    • people who have received a blood transfusion or blood products prior to 1985 in Australia, or from overseas
  • Patient request for an HIV test
  • A patient who reports having a reactive result on an unlicensed HIV test
  • Health-care workers conducting exposure prone procedures
  • In the context of post-exposure prophylaxis

Source: http://testingportal.ashm.org.au/hiv

Could it be HIV?

There are a number of conditions with an underlying prevalence of HIV of > 0.1%. In these situations it is essential to consider testing for HIV, as untreated and undiagnosed infection causes significant morbidity for the patient as well as increasing the risk of transmission.[19]

Some of these conditions are common and include STIs such as syphilis or gonorrhoea, herpes zoster, prolonged diarrhoea, mononucleosis-like illness and thrombocytopenia lasting for more than 4 weeks. AIDS-defining illnesses are in this list including pneumocystis pneumonia, CMV retinitis and non-Hodgkin lymphoma. A comprehensive list is provided in Table 2.[20] In these situations the clinician might say: “some people with your condition (e.g. thrombocytopenia) could have HIV, have you ever had an HIV test?”. This is a suggested introduction to an HIV test which can lead to pre-test discussion and consent to testing. Further questioning about risk and exposure can happen after this introduction and some clinicians might find this approach an easier way to introduce the topic.

Table 2. Definitions of indicator conditions and recommendations for HIV testing.[21]

 table2

AIDS: acquired immune deficiency syndrome; PLHIV: people living with HIV Source: HIV in Europe. Guidance: HIV in Indicator Conditions 2015.[22]

Rapid HIV testing or point-of-care testing

In December 2012, the Therapeutic Goods Association (TGA) approved the first point-of-care test for use in preliminary HIV screening in Australia. The point-of-care tests, also known as rapid tests, allow for on-the-spot HIV screening with results delivered to the patient at the same appointment. The TGA has outlined strict conditions for the use of these tests, to ensure quality of patient care. Reactive results must be followed up with a venous blood sample, sent to a diagnostic laboratory for confirmatory testing.

Informed consent for testing and conveying HIV test results

Informed consent for testing means that the person being tested agrees to be tested on the basis of understanding the testing procedures, the reasons for testing and is able to assess the personal implications. Obtaining consent is also an opportunity to provide information and support around the testing procedure, to minimise the personal impact of diagnosis, to change health-related behaviour and to address the anxiety of the person being tested. The discussion process also allows the clinician to assess risk, to educate the patient regarding risk of transmission, to obtain informed consent and to follow up and arrange referrals as indicated (Table 3).

Table 3. Gaining informed consent: discussion points[23]
  • Reason for testing and risk assessment
  • Timing of risk and option of post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP)
  • Need for other sexually transmissible infection (STI) and bloodborne virus testing
  • History of previous HIV testing
  • Confidentiality and privacy issues around testing
  • Natural history and transmission information (if appropriate)
  • Prevention of transmission and risk reduction through behaviour change Implication of a positive test result, including availability of treatment
  • Implications of a negative test result
  • Explanation of the window period
  • General psychological assessment and assessment of social supports in the event of a positive result
  • Logistics of the test: time taken for results to become available and the method of delivery of results.

During the discussion process, information is exchanged and concerns explored. Coping strategies are developed that may be used in the event of a positive result. While discussion does not need to proceed according to any formula, key information areas need to be covered during the consultation. Formal counselling is frequently required in the management of a person who has tested positive, or in the situation where a person who tested negative is continuing to participate in high-risk behaviours for HIV. This counselling is usually specialised and may require referral to an appropriate service or practitioner.

The discussion should be performed in a way that is relevant and appropriate to the person’s gender, culture, behaviour, language, and his or her understanding of HIV testing and testing history. That is, the discussion that occurs with a high-risk man who has sex with men in a major city will differ from that which occurs with a pregnant Indigenous woman undergoing testing in a remote area of Australia.

How results are given should be discussed by the ordering clinician during the consultation when informed consent is gained. Table 4 outlines key points to discuss for both positive and negative results.[24] Where possible, all positive HIV test results should be given in person, however, the clinician ordering the test may consider delivery of HIV test results to patients by telephone or by another mutually agreed method in some cases. Refer to the National HIV Testing Policy: http://testingportal.ashm.org.au/hiv

Table 4. Conveying a confirmed positive or negative test result: discussion points[25]

First post-test consultation

  • Establish rapport and assess readiness for the result
  • Know referral pathways, both clinical and psycho-social

Give positive test result

  • Avoid information overload
  • Listen and respond to needs (the patient may be overwhelmed and hear little after being told the positive result)
  • Discuss the immediate implications and treatment options including the advantages of early treatment.
  • Review immediate plans and support
  • Reassess support requirements and available services
  • Arrange other tests and the next appointment
  • Begin contact tracing process and discuss options available to facilitate this
  • Discuss the legal requirements regarding disclosure to sexual partners

Subsequent consultations

  • Encourage early treatment uptake
  • Effect of diagnosis on relationships and prevention information, issues of disclosure
  • Assessment of contact tracing process and difficulties encountered
  • Workplace implications
  • Impact of other issues (e.g. drug use, poverty, homelessness) on ability to access health care and treatments
  • Referral for on-going counselling, social worker, medical specialist as appropriate

Key points of conveying a negative result

  • Explain the negative test result and the window period (if relevant)
  • Reinforce education regarding safer behaviours
  • Consider vaccination – for hepatitis B and, if indicated, hepatitis A (in men who have sex with men) and human papillomavirus (HPV)
  • Further discuss anxiety or risk behaviours
  • Discuss testing for other STIs.

Key points of conveying a positive result

  • Ensure privacy and undertake the consultation in an area where you will not be interrupted.
  • Discuss treatment options
  • The information and support may be provided over a number of consultations and discussion should include those points listed

HIV Management

Starting antiretroviral therapy

New Australian guidelines recommend starting ART in all people living with HIV. This recent revision of the guidelines is based on the results of the START study that found that there were fewer clinical events in people randomised to immediate treatment versus patients deferring treatment.[26]

As well as the individual benefits of early treatment, the greatly reduced risk of transmission of HIV to sexual partners is an additional consideration. Before commencing treatment all patients should have some baseline investigations performed. These will be similar to those recommended for regular monitoring with the addition of a HIV genotype resistance test. Screening for tuberculosis and other infectious diseases should be considered.

There are now over 25 individual antiretroviral medications within six major classes of HIV agents available in Australia (Table 5). These agents work at different stages of the viral lifecycle to suppress viral replication. Although the particular first-line agents have changed, the general principles of effective therapy have been established over the last 20 years. This approach recommends that the patient should take a combination of three medications that together result in durable suppression of HIV replication. Modern combination ART most commonly consists of a backbone of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI/NtRTI) and a third agent which is chosen from another class. The third agent may be a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI). Note that if a PI is used it will commonly be combined with a low dose of ritonavir, which is a pharmacokinetic enhancer (or boosting agent) or other PI that allows once daily dosing. A new boosting agent is cobicistat which has been licensed in 2015 in Australia.

Table 5. Antiretroviral drug classes
  1. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
  2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  3. Protease inhibitors (PIs)
  4. Fusion inhibitors (FI)
  5. CCR5 antagonists
  6. Integrase strand transfer inhibitors (INSTIs)

The currently recommended first-line funded ART combinations are shown in Table 6. The development of new agents and regimens of medication is rapid in HIV medicine and guidelines are updated regularly to reflect advances. Currently it is recommended that first-line therapy include an integrase inhibitor based on its tolerability, efficacy and ability to rapidly lower viral load.[27]

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Table 6. Recommended regimens for first-line HIV treatment in Australia
Recommended regimens Brand name Comments

 INSTI-based regimens:

• DTG/ABC/3TC

• DTG plus TDF/FTC

• EVG/c/TDF/FTC

• RAL plus TDF/FTC

 

PI-based regimens:

• DRV/r plus TDF/FTC 

 

Triumeq

Tivicay plus Truvada

Stribild

Isentress plus Truvada

 

 

Prezista/Norvir plus Truvada

 

One tablet daily, check HLB5701

Two tablets daily

One tablet daily  with food

Three tablets daily

 

 

Four tablets daily (not licensed in Australia for initial treatment)

3TC: lamivudine; ABC: abacavir; ARV: antiretroviral; DRV/r: ritonavir-boosted darunavir; DTG: dolutegravir; EVG/c/TDF/FTC: elvitegravir/cobicistat/tenofovir/emtricitabine; FTC: emtricitabine; INSTI:integrase strand transfer inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; RAL: raltegravir; RTV: ritonavir; TDF: tenofovir disoproxil fumarate

The choice of medication will involve discussion about potential side effects, drug interactions, dosing requirements (e.g. timing, food restrictions), other health problems, potential for pregnancy and patient preference. As with other chronic health problems no perfect drug exists, however patients can now expect few side effects and convenient dosing – very important issues for medication that will need to be taken long term. Once started, medications should be taken indefinitely.

A change in treatment may be required for reasons such as side effects, the development of resistance to first-line treatment or in special situations such as pregnancy. Advice from experienced practitioners should be sought in these situations.

In making the decision to treat, consideration must be given to the patient’s commitment to therapy, his or her awareness of the importance of strict adherence to the regimen, and the potential for adverse effects. Advice regarding the decision can be obtained from an experienced antiretroviral HIV prescriber.

Monitoring antiretroviral therapy

Regular monitoring

Monitoring and the Role of the GP

Patients will require regular monitoring of their immune function and will need more intense monitoring after starting or changing ART. Once stable however, 6-monthly reviews of HIV viral load and CD4 count are considered sufficient. At these review visits, adherence, side effects and possible drug interactions and STI testing needs are also checked. Periodic biochemistry and urinalysis is performed to check for toxicity. The HIV prescriber (frequently, a GP who has undertaken additional training) will normally perform these tests.

Patients require close monitoring in the first few months of treatment with ART. Side effects are most likely at this time and medication may need to be modified. With antiretroviral treatment, the level of HIV in the blood (called the HIV viral load) will generally become undetectable after 3 months. That is, the HIV RNA level is less than the limit of detectability used by the pathology laboratory, which is now less than 20 to 40 copies/mL.

Suppression of viral replication will be associated with reduced CD4 cell loss and recovery of the CD4 count. CD4 count recovery is a much slower process lasting several years, and the rate of recovery varies significantly among patients. Once stable on treatment with an undetectable HIV viral load, the frequency of HIV monitoring can be reduced to every 3-6 months.

The emergence of resistant HIV and virological treatment failure may be indicated if the HIV viral load does not become undetectable or it increases after starting treatment. This situation most often results from adherence difficulties. Intermittent low levels of detectable virus (up to 200 copies/mL), called virological blips, may occur without indicating the development of resistance.

Monitoring visits will involve a targeted history, examination and pathology testing. As well as HIV viral load and CD4 count, full blood count (FBC), liver function tests (LFT) and urea, creatinine and electrolytes (UEC) should be checked. Investigations such as fasting glucose and lipid levels and urinalysis should be performed every 12 months. The recommended periodic monitoring and preventive health activities are listed in Table 7.[28] Some specialist HIV services do not address non-HIV issues such as STI screening and Pap smears: it may be assumed that the GP is attending to these issues. GPs should expect to be sent copies of investigations.

Table 7. Assessment and monitoring of the patient with HIV infection[29]
BMI: body mass index; BP: blood pressure; CNS: central nervous system; HDL: high-density lipoprotein; LDL: low-density lipoprotein
All visits Annual reviews
History and symptom review Assessment of immunity to hepatitis A and B and vaccination if susceptible, hepatitis C antibody if at risk
Psychosocial assessment and support Influenza vaccination, (pneumococcal vaccination see guidelines)
Patient education (e.g. transmission, treatment options) Cervical cytology by PAP smear
Health promotion (e.g. safe alcohol use, smoking cessation) Fasting cholesterol (including HDL and LDL), triglycerides and glucose
Urinalysis
6 monthly review Cancer screening as per guidelines (colon, breast)
Weight, BMI, BP, waist circumference Cardiovascular risk calculation
   
Full blood count Physical assessment for lipodystrophy (fat wasting, fat accumulation)
Liver function tests Review risks for osteoporosis
Renal function Refer for annual dental check
CD4 cells count, HIV viral load Additional monitoring for patients taking antiretroviral therapy
STI screening including syphilis serology (depending on risk group) Frequent review during the first month of treatment by prescriber
  Monitoring for severe side effects (e.g. hypersensitivity, CNS toxicity, neuropathy)
  Management of treatable side effects (e.g. nausea, diarrhoea)
  Adherence monitoring and support
  Review possible drug interactions

Patient education and support

Patient education and support should be provided at every monitoring visit.

Adherence

Adherence should be assessed at every monitoring visit. Older HIV medications were very demanding in their dosing requirements, requiring greater than 95% adherence to maintain HIV control.[30] Newer medications have longer half-lives and are more forgiving, but high levels of adherence are still needed. Adherence can be enquired about with permissive questions such as: “Many people have trouble taking their medications every day, have you had any difficulties recently?” The use of simple adherence aids such as pill boxes may also be helpful.

Medication must be taken properly to be effective in the long term. If the patient is regularly missing doses, not following dosing recommendations or has commenced a new medication (including over-the-counter and complementary) which affects the metabolism of the drugs, the reduced concentration of antiretroviral agent allows for the selection of drug-resistant HIV and failure of the antiretroviral regimen. Unfortunately, there is often significant cross-resistance within the same class of antiretroviral drugs and resistance to one drug may reduce response to subsequent regimens. If the patient reports poor adherence, discussion with the HIV prescriber may be appropriate to consider simplification of the antiretroviral regimen (e.g. to a single tablet regime) to make adherence easier. Management of side effects may also improve adherence.

Side effects

Side effects should be reviewed at each visit. Many patients may be experiencing significant side effects but may not report these unless asked specifically. The presence of side effects is associated with reduced adherence and poorer quality of life. Again general questions should be asked, followed by more specific questions targeted at common side effects associated with particular regimens (e.g. presence of diarrhoea, or sleep disturbance and mood changes).

Drug interactions

Drug interactions should be considered at each regular visit including prescribed, over-the-counter medications, supplements and recreational drugs. Some common interactions between antiretroviral drugs and other agents (includes recreational drugs) are shown in Table 8. Interactions can be complex as commonly used antiretroviral drugs can induce or inhibit hepatic drug metabolism. The new combination medication, Stribild, now available in Australia, includes cobicistat, a pharmacokinetic enhancer, as well as tenofovir, emtricitabine and elvitegravir. Cobicistat has similar drug interactions to the widely used PI ritonavir as both inhibit the CYP3A4-mediated hepatic metabolism of many agents. Detailed support can be obtained from online reference tools such the University of Liverpool’s website www.hiv-druginteractions.org.

Table 8. Common interactions between antiretroviral drugs and other drugs*[31]
Drug class Interaction with antiretroviral drug Comment

Acid lowering:

proton pump inhibitors

 

H2-receptor antagonists

 

antacids (containing magnesium, aluminium, calcium)

 

↓ atazanavir, rilpivirine

 

↓ atazanavir, rilpivirine

 

↓ dolutegravir, elvitegravir, atazanavir, ripivirine

 

Avoid proton pump inhibitors, take care with other acid reducers

Complex dosing, see product information

Avoid co-administration but can be taken at different times, see product information

Antiarrhythmics, e.g. amiodarone ↑ with PI, cobicistat Avoid amiodarone and other antiarrhythmics

Anticoagulants and antiplatelet

Complex

Check online (aspirin and heparin are safe)

Anticonvulsants: carbamazepine, phenobarbital, phenytoin

 ↓ etravirine, rilpivirine, lopinavir

 Avoid, take care with other PI

Antidepressants ↑ with PI, cobicistat Start with low dose and titrate slowly

Antihypertensives:

calcium channel blockers

 

beta-blockers

 

 

↑ with PI, cobicistat; ↓ with NNRTI

 

↑ with cobicistat

 

Dose adjustment (avoid lercanidipine)

 

Dose adjustment

Antidiabetic:

metaformin

 

↑ with dolutegravir

 

Dose adjustment

Antipsychotic

quetianpine, pimizide

 

↑↑ with ritonavir, cobicistat

 

Avoid

Benzodiazepines:

midazolam, triazolam

 

 

↑ with most ART

 

Avoid

Bronchodilator: salmeterol

 

↑↑ with ritonavir, cobicistat.

Avoid

Corticosteroids: inhaled or intranasal fluticasone, budesonide

↑↑ with ritonavir, cobicistat. Can result in adrenal insufficiency, including Cushing’s syndrome

Avoid, use beclomethasone

Corticosteroids: systemic, including articular injections

Complex, risk of ↓ ART and ↑↑ corticosteroid

Use with care, prednisone is safest

Gout: colchicine

↑ with PI, cobicistat

Reduce dose

Hormonal contraceptives

↓ with PI, NNRTI, cobicistat

Complex – consult guidelines

Migraine: ergotamine

↑↑ with most ART

Avoid

Narcotics:

Methadone

buprenorphine

 

↓ with nevirapine, efavirenz

↑ with atavanavir (unboosted)

 

May need dose increase

Avoid

Phosphodiesterase type 5 (PDE5) inhibitors e.g. sildenafil ↑ with PI, cobicistat Start with low dose

Statins

simvastatin, lovastatin,

atorvastatin, rosuvastatin

 

↑↑ with PI cobicistat

↑ with cobicistat

 

Avoid, use other statins

Reduce dose

Stimulants such as MDMA (ecstasy), cocaine ↑ with ritonavir, cobicistat Warn patients of the risk

St John’s wort

↓ level of many ART

Avoid

ABBREVIATIONS: ART = antiretroviral therapy; MDMA = 3,4-methylenedioxy-N-methylamphetamine; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor.

*Does not include interactions with other antiretroviral drugs or more specialised drugs such as those used to treat tuberculosis or hepatitis C.

 

Other monitoring

Most other monitoring is in line with standard GP care, as detailed in the RACGP Red Book[32] and the Immunisation Handbook.[33]

Preventing other infectious diseases

Historically most patients with HIV infection experienced life-threatening infections such as PJP. People with a low CD4 cell count of less than 200 cells/L remain vulnerable to serious infections. This group needs to continue with appropriate antibiotic prophylaxis, most commonly sulfamethoxazole/trimethoprim (usual dose two double strength tablets twice a week). Most patients in regular care will have a CD4 over 200 cells/L so will not require antibiotic prophylaxis.

Vaccination is less effective for individuals with severe immune suppression (CD4 cell count below 200 cells/L)[34] All patients should be screened for hepatitis A, B and C. Susceptible patients should receive vaccination for hepatitis A and B.[35] The levels of antibodies against the hepatitis B surface antigen (anti-HBs) should be checked and patients revaccinated to maintain an anti-HBs level above 10 mIU/mL (i.e. a seroprotective level).

People at risk for hepatitis C (men who have sex with men, people who inject drugs) should have annual antibody tests. Early referral of HIV-positive patients with new hepatitis C virus infection to a hepatitis treatment centre for assessment should be considered. Chronic hepatitis B can be treated with commonly used ART which would influence the choice of regimens.

Respiratory infections are more common in this patient group. All patients with HIV infection should have annual influenza vaccinations and periodic pneumococcal vaccinations.

Many HIV-positive people travel and will need to consider travel-related vaccinations. In general, vaccination of such patients is safe with all inactivated vaccines and some live attenuated vaccines (measles, mumps, and rubella [MMR] and varicella vaccines). However, vaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis, oral polio and oral typhoid vaccines is contraindicated. Yellow fever vaccination can be given if significant risk exists, provided the CD4 cell count is above 200 cells/L. Vaccination for human papilloma virus is safe and immunogenic in HIV-positive people but is currently not funded.

STIs should be screened for as recommended in current guidelines.[36] All men who have sex with men are advised to have 3 to 12 monthly checks for STIs, including gonorrhoea, chlamydia and syphilis. Other groups should be screened opportunistically.

Lifestyle factors

Modifiable risk factors are very important in this population. Smoking particularly is more prevalent and has been shown to be associated with multiple complications including pneumonia, lung cancer and cardiovascular disease.[37] Approaches to monitoring and interventions are similar to those for the general population. Motivational interviewing and other lifestyle interventions such as ‘Smoking, Nutrition, Alcohol and Physical activity (SNAP)’ provide a useful framework for patient counselling.[38]

Screening for cardiovascular and metabolic disease

Cardiovascular disease is more common in people living with HIV.[39] Risk factors such as smoking are more prevalent but HIV itself appears to increase the risk of ischaemic heart disease (IHD) by about 75%.[40] Patients should have their absolute cardiovascular risk calculated using a tool such as the Australian calculator at www.cvdcheck.org.au.

Diabetes, hyperlipidaemia and abnormal fat distribution (lipodystrophy) are also more common. The causes of these comorbidities are complex and involve the effects of the virus as well as side effects from some antiretroviral medications.[41]

All patients require monitoring in line with standard guidelines for screening for cardiovascular and metabolic disease. Blood pressure and weight should be checked regularly, and fasting lipids and glucose levels should be measured at least annually. ART may need to be switched to reduce metabolic complications if they are thought to be medication related. This can be a complex decision as it is still most important to maintain good control over the HIV infection. Treatment is generally similar to the general population, with the exception that certain medications (e.g. simvastatin) should be avoided, as indicated in Table 7.

Fat wasting (lipoatrophy) and fat accumulation make up the lipodystrophy syndrome. This condition is now rare with modern treatment but is of great concern for patients who were treated with older regimens. Lipoatrophy can be partly corrected with the use of fillers such as poly-L-lactic acid but is best avoided by switching to newer ART agents.

Monitoring renal, liver and bone disease

As with metabolic disorders there is a complex relationship between HIV infection, comorbidities (such as viral hepatitis) and ART in the pathogenesis of renal, liver and bone disease.

Renal function should be monitored regularly, especially when starting new medications. Urea, Electrolytes and Creatinine (UECs) should be performed every 3 to 6 months, and urinalysis annually. Potentially nephrotoxic medication such as tenofovir needs more intense monitoring. Renal toxicity such as a decline in eGFR, proteinuria or renal calculi may require a change in therapy.

Liver function tests should also be checked regularly, and especially when starting ART and in the presence of other causes of liver disease. Most antiretroviral medications can cause hepatotoxicity.

Osteoporosis is more prevalent in people with HIV infection than in the general population. Monitoring and treatment remains similar to that in the general population.

Screening for malignancies

The incidence of some malignancies is much higher in the presence of HIV infection. These are cancers related to co-infections such as with human papillomavirus (HPV), hepatitis B and C, Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8). For this reason, annual Pap smears are advised for female patients.

Many common cancers (such as breast, bowel and prostate cancers) are no more frequent in this population so no changes in standard cancer screening are indicated apart from more frequent Pap tests. Vigilance is needed for the detection of new skin lesions that could be Kaposi sarcoma. These are often non-specific and therefore require biopsy.

Anal cancer is also much more common in those with HIV infection, but there is no agreed screening test at this point. Any anal symptoms, including rectal bleeding, pain or lumps, should be promptly investigated.

Monitoring for depression and psychosocial problems

Depression is very common in men with HIV infection, with a prevalence of about 30%.[42] Assessment of mood can be performed opportunistically. People living with HIV also frequently experience discrimination and occupational, housing and financial disadvantage. Referral to a psychologist or peer support worker can be helpful.

Neurocognitive impairment is also more common in this population, however screening is controversial. Consider specialist referral if patients report symptoms such as memory loss, poor concentration or other cognitive difficulties.

Alarm symptoms

Table 9 lists some clinical presentations that may require urgent action. Sometimes patients present with unknown or low CD4 (< 200) in which case the GP needs to consider possible opportunistic illness. If a patient is unwell they need urgent hospital referral. If stable they can be investigated as an outpatient. If in doubt seeks specialist advice.

Table 9. Clinical presentations that may require urgent action in patients with HIV infection
Symptom Possible cause Consider Chapter
Respiratory symptoms in patient with unknown or low CD4 PJP, bacterial pneumonia, tuberculosis Urgent review with X-ray, induced sputum for PJP Respiratory infections
Visual loss in patient with unknown or low CD4 Now rare – CMV retinitis Urgent ophthalmology review Ophthalmic diseases
Headache  in patient with unknown or low CD4 Meningitis, cerebral toxoplasmosis, lymphoma Urgent brain CT/MRI, may also need lumbar puncture and hospital admission

Toxoplasmosis

Cryptococcal meningitis

Swallowing difficulties  in patient with unknown or low CD4 Likely to be oesophageal candidiasis if oral thrush seen Start  fluconazole with regular reviews Oesophageal candidiasis
Severe rash after starting new medication Hypersensitivity reaction Review medications, differential,  may require drug cessation Managing the patient on antiretroviral therapy
Severe depression, suicidal thoughts Major depression Assess risk of self-harm Psychiatry and HIV

Decline in renal function, proteinuria

Nephrotoxicity from medications Check UECs, MSU, protein/creatatine ratio,  renal USS, review medication Renal disorders
Raised liver enzymes Hepatotoxicity from medication, viral hepatitis infection Check viral serology, review medication,

Managing the patient on antiretroviral therapy

Hepatitis B co-infection

Hepatitis C co-infection

Rectal bleeding,  anal mass or other symptoms Anal cancer Thorough examination, specialist referral for biopsy Oncological conditions
Memory or other cognitive problems Dementia Neuropsychologist, neurologist, possible intensification of HIV therapy Neurological disorders
Detectable HIV viral load

Adherence problems

Viral resistance

Patient counselling, take sample for HIV genotyping Managing the patient on antiretroviral therapy
Pregnancy     Start antiretroviral therapy HIV and pregnancy

CMV: cytomegalovirus; MSU: midstream specimen of urine; PJP: Pneumocystis jirovecii pneumonia; UECs: Urea, Electrolytes and Creatinine

Providing care to diverse populations

Health needs for people with HIV infection will vary greatly depending on their background. The distribution of newly diagnosed HIV in Australia is shown in Figure 5.[43]

Figure 5. Newly diagnosed HIV infection and diagnoses of newly acquired HIV infection in Australia, 2009 – 2013, by HIV exposure category

fig5

Source: Kirby Institute. Annual Surveillance Report 2014.[44]

Men who have sex with men

Gay men and men who have sex with men are the largest population of people living with HIV with 75% of all HIV infections diagnosed in Australia with recorded exposure category due to male homosexual contact.[45] HIV prevalence is estimated to be 8–12% among gay community-attached men in Australia.

This population has high rates of psychological comorbidity including depression and drug and alcohol use.[46][47] Specialist counselling services are widely available in large cities.

Women

About 2000 women are living with HIV in Australia.[48] The major risk factor reported in this population is heterosexual exposure. This group have major concerns regarding sexual and reproductive issues. Annual Pap smears are recommended however data from sexual health clinics suggest that most patients are not having annual screens.[49]

Heterosexuals

Heterosexual males with HIV infection are a minority in Australia with an estimated population of 5629.[50] They are a diverse group requiring appropriate care depending on their cultural and ethnic backgrounds.

Aboriginal and Torres Strait Islanders

HIV is uncommon in Aboriginal and Torres Strait Islander people with an estimated population of 492 and a prevalence of 0.15%.[51] A higher proportion of HIV cases in this population was attributed to injecting drug use (12%) or heterosexual contact (21%) compared with the non-Indigenous population (3% and 13%).

Culturally and Linguistically Diverse people

An estimated 2559 people living with HIV were born in South East Asia and 2126 were born in sub-Saharan Africa.[52] Treatment access can be complex in this population due to lack of residency status and access to Medicare.[53]

Adolescence and children

HIV transmission from mother to child is now a rare event. Between 2004 and 2013 of 372 children born to women with HIV only 13 cases of HIV infection occurred.[54] In over half of these cases, the woman was diagnosed with HIV after the birth of the child. HIV testing is recommended as part of standard antenatal screening. Care of this population is complex and is usually provided in specialist centres.

HIV prevention

There are a number of points at which HIV infection can potentially be prevented.[55] As there is no effective vaccination available other approaches to prevention have been extensively investigated. Historically most interventions have focused on behavioural interventions such as safer sex campaigns. GPs have a role to play in encouraging condom use and in providing treatment for people who inject drugs.

Over the last few years data have emerged that treatment of those with HIV infection greatly reduced the risk of disease transmission. This approach is termed treatment as prevention and the related “test and treat” approach. GPs have a vital role in encouraging frequent testing of at-risk populations and in encouraging early treatment for those found to have HIV infection (Table 10).

Table 10. HIV prevention approaches

For those at risk of HIV infection

At the time of  exposure to HIV Following exposure to HIV With HIV infection

Condoms, male circumcision, ‘safe sex counselling’, treatment for people who inject drugs  (e.g. needle and syringe programs, opioid substitution)

Pre-exposure prophylaxis (PrEP), microbicides, antiretrovirals to prevent mother-to-child transmission

Post-exposure prophylaxis (PEP)

Antiretroviral treatment to reduce infectivity – called treatment as prevention (TasP)

Post exposure prophylaxis (PEP) has been widely available in Australia for many years. The early research focused on occupational exposure to HIV through needle stick injuries in hospital settings. More recently PEP has been available for sexual and other non-occupational exposures. Current PEP treatment is the use of antiretroviral agents for 4 weeks following exposure. Guidelines advise that PEP should be started within 72 hours of exposure. Initial supplies of treatment are provided to emergency departments and to GPs with high case loads of patients. Treatment is usually given with two to three antiretroviral agents.

Multiple approaches appear to be needed to reduce new HIV infections. There is now very strong data to support the use of pre-exposure prophylaxis (PrEP) which involves the use of antiretroviral agents by people who do not have the infection but are at risk of HIV infection. This treatment is now licensed but not funded in Australia. An increasing number of patients are currently being treated with PreP in trials or with imported antiretroviral medication. This approach can be discussed with people at risk who can be directed to online information discussing treatment access.[56] The cost-effectiveness of providing PrEP is complex and very dependent on drug pricing.[57]

The role of the GP

GPs have a vital role to play in the early diagnosis of HIV by offering regular HIV testing for those at risk. Most patients will then need life-long treatment with antiviral medications, which may be provided by HIV specialists or by GPs with advanced training. In addition, patients will continue to need comprehensive general practice care.

As with other chronic medical conditions, the primary care doctor can play a pivotal role in the care of patients with HIV infection as a provider of routine care and coordinator of referral to specialist care. Patients living with HIV will require differing levels of engagement with specialist care depending on their particular circumstance. When patients are newly diagnosed or considering treatment for the first time, specialist input is necessary. If patients have complex comorbidity issues, engagement with several specialists is common. However, many HIV-positive patients are stable and doing well on antiretroviral therapy, so they choose to visit specialists every 6 to 12 months and access the majority of their care in general practice.

The concept of models of care has emerged as a way of describing elements of the health-care system in a meaningful manner. There does not appear to be an agreed upon definition of model of care; however one definition referred to by several authors is : a multifaceted concept, which broadly defines the way health services are delivered (Figure 6).[58] Multiple models have been defined such as shared care programs, case management, transitional care, stroke units and cardiac rehabilitation programs.

Figure 6. Models of HIV care in general practice in Australia

 

 

GP HIV specialist model

The specialist GP model (sometimes called S100 GPs after Section 100 of the Pharmaceutical Benefit Scheme) has been highly developed in Australia with GPs attending training programs and then prescribing ART for over 20 years. There are highly developed training programs with continuing medical education courses conducted around Australia. See National standards for community HIV S100 prescriber training and certification and nationally endorsed curriculum for HIV education programs at ASHM.[59] There is evidence that care provided in HIV specialised general practice is comparable to specialist clinics.[60][61]

Shared care model

Some GPs provide components of HIV care alongside general practice care but do not prescribe ART. They generally work closely with the prescribing doctor who may be a medical specialist or an S100 GP. This collaboration can be referred to as shared care provided certain criteria are met. Hickman has defined shared care as the joint participation of primary care physicians and specialty care physicians in the planned delivery of care informed by an adequate education program and information exchange over and above routine referral notices.[62] This could take the form of regular communications such as the exchange of care plans or case conferences or by a visiting specialist clinic in the general practice.

Specialist referral model

Many GPs have little or no contact with people living with HIV so the traditional model of referral to a specialist for HIV care is appropriate. All GPs should be able to perform HIV testing with appropriate counselling. However there is evidence that many GPs have poor knowledge of HIV testing and treatment.[63] Telephone support is available for low-case load GPs making a new diagnosis in most parts of Australia.

GP training

GP training in HIV medicine is provided by a number of providers around Australia but the major provider is ASHM which conducts training programs in most states as well as administering the S100 and continuing medical education programs. Currently approximately 200 GPs have completed S100 training as well as the ongoing continuing medical education requirements.

Summary

As HIV has become a long-term manageable health condition the role of the GP has evolved. Initial focus has been on diagnosis, which remains important, but has now shifted to life-long patient care. Recent data support ART from the time of diagnosis, which although highly effective, demands a high level of adherence by a patient. The GP is ideally placed to support patients with life-long therapy as well as providing the full range of recommended preventive health care to ensure that patients live long healthy lives.

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