The treatment of HIV infection has progressed enormously since the first cases of Acquired Immune Deficiency Syndrome
(AIDS) were described in 1981.1 Before the discovery of antiretroviral medicines, people with HIV would experience
a progressive decline in T4 lymphocytes (“helper T cells”).1 These cells have the CD4 molecule on their surface
which acts as the primary receptor for HIV infection.1 Without treatment, the patient’s CD4+ T cell count
would decline over approximately five to ten years to the point where they developed AIDS and became highly vulnerable
to life-threatening infections.1 Following the advent of antiretroviral medicines the prognosis of people
infected with HIV improved substantially. Diagnoses of AIDS have dropped dramatically in countries with subsidised access
to antiretrovirals and the life expectancy of a 20-year old infected with HIV today is approximately 70 years.1 Another
advantage of antiretrovirals is that they can reduce the patient’s HIV load to a level where they can no longer transmit
the infection to other people.
The strategies to prevent new HIV infections
The goal in New Zealand is to eradicate new HIV infections by 2025.2 A combination prevention strategy
is being implemented to achieve this:
- Consistent and correct use of condoms; the use of condoms decreases the risk of acquiring HIV infection by approximately 90%3
- Regular testing, particularly focused on those at increased risk of HIV and STIs, e.g. men who have sex with men (MSM)
- Early diagnosis and prompt treatment of people living with HIV to reduce their viral load and therefore avoid transmitting the infection to others
- Targeted use of HIV Pre-Exposure Prophylaxis (PrEP) for groups at high-risk of HIV infection, i.e. MSM who do not
regularly use condoms or people with a partner who has a detectable HIV viral load
The combined approach of condoms, regular testing, early treatment and HIV PrEP has been effective for groups of people
with ready access to healthcare. For example, the New South Wales HIV Strategy in Australia has reported a 49% decrease
in the number of Australian-born MSM diagnosed with early-stage HIV infections in the first half of 2018.4 However,
the lack of a similar outcome for other groups, e.g. Aboriginal Australians or recent immigrants, highlights the importance
of equitable access to healthcare for the success of this approach.
HIV in New Zealand: where are we at?
New HIV infections in New Zealand dropped in 2017, for the first time in six years.9 However, it is too early
to tell if this is the beginning of a downward trend. In 2017, there were 197 people with new HIV infections recorded in
New Zealand, 38 of whom had been previously diagnosed overseas.9 There are approximately 3,500 people infected
with HIV living in New Zealand.10
Most new HIV infections occur in men who have sex with men
HIV infections predominantly occur in MSM,8 who accounted for the majority of those diagnosed with locally
acquired infections in 2017 (Table 1).9 There are multiple reasons why MSM are at increased risk of HIV infection
compared with heterosexual people:1, 11
- Receptive anal intercourse has a higher risk of HIV infection than vaginal intercourse because the rectal mucous membrane
separating deposited semen from cells susceptible to infection is thinner and the surface area of mucosa exposed
to the virus is much larger
- The ratio of MSM in New Zealand who are infected with HIV is higher than the general population; 37 times higher compared
to heterosexual males
- The sexual networks of MSM are closer and as they are a minority within the general population, the transmission of
STIs between sexual contacts is more likely
It appears that HIV infection is being diagnosed earlier in New Zealand MSM, allowing for prompt treatment, potentially
limiting the spread of the disease and preventing progression to AIDS. This conclusion is supported by the average CD4+
count at diagnosis increasing since 2006, suggesting a less depleted immune system in those diagnosed.9 Injectable
drug use is now a rare cause of HIV infection, with only one recorded case in 2017, due to the early and successful implementation
of needle-exchange programmes in New Zealand.9
Heterosexual females are at higher risk than heterosexual males
Among heterosexuals, females have twice the risk of males of being infected by a partner with HIV because the virus is
concentrated in seminal fluid.1, 3 However, the number of cases of HIV infection recorded in heterosexual males*
and females was the same (12) in New Zealand in 2017 (Table 1).9
* It is possible that some cases of HIV infection reported in heterosexual males were actually in MSM who did not disclose
their same-sex contact
Table 1: Patient characteristics for new HIV cases in New Zealand in 2017 9
MSM cases (n=128) |
Heterosexual cases (n=24) |
Ethnicity
- European – 54%
- Asian – 22%
- Māori – 6%
- Pacific peoples – 6%
- Other/unknown – 12%
Location
- Auckland – 43%
- Wellington – 22%
- North Island other regions – 12%
- South Island – 9%
- Overseas – 7%
- Unknown – 7%
|
Gender
Ethnicity
- Asian – 42%
- European – 25%
- Māori – 8%
- African – 8%
- Other – 17%
|
AIDS is decreasing in New Zealand
HIV disease is a spectrum that begins with acute infection, that if left untreated, progresses to AIDS, which is invariably
lethal due to opportunistic infections and cancers.1 In New Zealand, deaths due to AIDS peaked at approximately
70 per year in the late 80s and early 90s, and although there have been fluctuations in the rate there has been a consistent
downward trend ever since. Latest figures from 2017 show 12 people were notified with AIDS (11 males, 1 female).9 Five
of those were diagnosed with AIDS within three months of being diagnosed with HIV, suggesting that they had been infected
with HIV for a substantial period of time.9 Increasing the uptake of regular HIV testing is crucial to avoid
diagnosis at the stage of AIDS.
New Zealand became one of the first countries in the world to fully subsidise oral emtricitabine with tenofovir disoproxil
for HIV infection prophylaxis under Special Authority approval in March, 2018.5 HIV PrEP is a daily oral tablet
containing 200 mg emtricitabine and 245 mg tenofovir disoproxil. It greatly reduces the risk of HIV infection when taken
as prescribed.6 Emtricitabine and tenofovir disoproxil are reverse transcriptase inhibitors that prevent a
key step in the HIV replication cycle.7 These medicines cannot eliminate HIV from individuals with an established
infection.
Emtricitabine with tenofovir disoproxil can be co-prescribed in combination with other antiretrovirals for the treatment
of HIV. It can also be used for Post-Exposure Prophylaxis (PEP) within 72 hours of a potential exposure to HIV (see: “HIV
Post-Exposure Prophylaxis [PEP]”).
A new brand of HIV PrEP, subsidised from 1 April, 2019
From 1 April, a new brand of PrEP is available fully subsidised, and will have sole supply in New Zealand from 1 September, 2019.
Emtricitabine/Tenofovir Disoproxil (supplied by Teva) contains the same medicine combination and dose as the other subsidised brand of PrEP, Truvada.
There is a difference in the tenofovir disoproxil salt between the brands; the Teva formulation contains tenofovir disoproxil succinate, and Truvada
contains tenofovir disoproxil fumarate. However, both formulations are equivalent to 245 mg tenofovir disoproxil.
It is recommended that PrEP is prescribed using the generic medicine name; emtricitabine + tenofovir disoproxil.
From 1 June, 2019, the subsidy of Truvada will be reduced and the brand will be delisted from 1 September, 2019. The
brand change should be discussed with patients who are currently using Truvada.
N.B. Teva is not the brand name of this medicine, it is the supplier (sponsor). Care must be taken not to inadvertently prescribe Tenofovir Disoproxil alone,
also supplied by Teva.
PrEP is highly effective when taken exactly as prescribed
Seven days after beginning daily treatment with PrEP a person’s risk of infection via rectal exposure to HIV is almost
entirely eliminated;8 a few extra days of PrEP may be required for vaginal and cervical tissues to be maximally
protected from vaginal HIV exposure. PrEP is continued for as long as the patient remains at risk (see: “Monitoring
treatment and maintaining adherence”). Condoms are strongly recommended for at least the first seven days of treatment.
The risk of HIV infection is reduced by 99% with perfect adherence to PrEP, i.e. if the medicine is taken at the same
time of day, every day.6 The level of protection from rectal HIV infection provided by PrEP falls to 96% in
people taking four doses per week and 76% in those taking two doses per week.6 Strict adherence to daily PrEP
dosing is required to provide protection from vaginal HIV infection.8 If a patient who has been adherent to
daily PrEP withdraws from treatment or forgets to take their medicine, the protection provided by PrEP persists for approximately
seven days following the last dose.8
Continue to encourage the consistent use of condoms
It is important that patients who are prescribed PrEP understand that they will only be protected against infection
with HIV. Encouraging adherence to HIV PrEP and continuing to promote the consistent and correct use of condoms to prevent
other STIs is essential.
The Special Authority criteria for HIV PrEP are derived from the Australian Health In Men (HIM) study, that identified
the key factors associated with an increased risk of infection with HIV in MSM.12 Testing is required, both
prior to and following initiation of PrEP to receive subsidised treatment. It is estimated that 5,800 people in New Zealand
will be eligible for PrEP, including 18% of all sexually active MSM.13
Special Authority approvals need to be renewed every three months
Special Authority approvals for HIV PrEP are valid for three months and must be renewed every three months thereafter.
Special Authority initial applications and renewals for subsidised PrEP can be submitted by any relevant practitioner who is confident in their
knowledge of PrEP and ability to safely manage the patient’s treatment.
The Special Authority application form for HIV PrEP can be found here
Further information on prescribing HIV PrEP is available from:
https://www.nzaf.org.nz/prep-information-for-clinicians
Initiating subsidised PrEP
To initiate subsidised PrEP patients must have first tested negative for HIV and: Meet EACH of
the following characteristics:
- Male or transgender
- Has sex with males
- Likely to have multiple episodes of anal intercourse without condoms in the next three months
AND have at least one of the following:
- At least one episode of receptive anal intercourse with a male partner without condoms in the last three months; or
- A diagnosis of rectal chlamydia, rectal gonorrhoea or infectious syphilis in the last three months; or
- Use of methamphetamine* in the last three months
OR meet EACH of the following characteristics:
- Has a regular partner who has an HIV infection
- The partner has a detectable viral load or is untreated for HIV
- Condoms are not consistently used
* The use of methamphetamine is known to increase the likelihood of high-risk behaviour, e.g.
anal sex without condoms, group sex, multiple sex partners and injecting drugs
Testing before initiating PrEP
Before applying for Special Authority approval the patient must have tested negative for HIV (see: “HIV
Post-Exposure Prophylaxis [PEP]” for information on managing patients at high risk of HIV infection due to recent exposure).
Guidelines and sexual health specialists also recommend additional testing, including (Table 2):
- Blood tests for syphilis and hepatitis A, B and C – unless known immunity to hepatitis A or B
- Multi-site nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea (urine, rectal, vulvovaginal and throat
swabs as appropriate)
- Estimated glomerular filtration rate (eGFR), serum phosphate and creatinine, urine dipstick (to detect protein), albumin:creatinine ratio
- Full blood count
- Liver function tests
- Pregnancy testing in people with childbearing potential
People with chronic hepatitis, can take PrEP, however, testing prior to initiating treatment is recommended
as there may be an increased risk of hepatic adverse effects.8 Consultation with a hepatologist or infectious
diseases physician experienced in treating chronic hepatitis is recommended before starting HIV PrEP
in patients with hepatitis B or C.8 Testing for hepatitis B virus (HBV) is particularly important because
emtricitabine and tenofovir disoproxil are both active against HBV and withdrawal of PrEP can lead to reactivation of
HBV and hepatic injury.8 Immunisation
against HBV, and demonstration of immunity, is recommended for all MSM who test negative for HBV prior
to initiating PrEP.8 Ongoing
testing for HBV is not necessary in immune patients unless there is an unexplained elevation in alanine
aminotransferase. Immunisation against hepatitis A virus is recommended for those who are not immune as it can be easily
sexually transmitted among MSM and transgender people who have sex with males, however, vaccination is not subsidised
in New Zealand.
People with a bacterial STI, e.g. chlamydia, gonorrhoea and syphilis, can take PrEP and this should
not be a reason to delay initiation.8 People taking PrEP are at high risk of STIs other than HIV. Therefore,
advice about use of condoms and initial and ongoing testing is required to detect any STIs, which should be treated promptly;
PrEP should be continued while the patient is being treated.
PrEP is contraindicated in people with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2,
as treatment with tenofovir has occasionally been associated with nephrotoxicity.8 Following initiation of
PrEP, it is recommended that the patient’s serum creatinine, eGFR, serum phosphate, urine dipstick (to
detect protein) and albumin:creatinine ratio*
be assessed at three months and at six-monthly intervals thereafter.8 More frequent monitoring may be appropriate
for patients who are more susceptible to clinically significant reductions in eGFR or who are at risk
of renal disease, including those who:8
- Are aged over 40 years; studies have shown that the use of PrEP in this age group is associated with a faster decline
in renal function14, 15
- Have an eGFR < 90 mL/min/1.73m2
- Are taking another nephrotoxic medicine long-term, e.g. non-steroidal anti-inflammatory drugs (NSAIDs)
- Have co-morbidities such as hypertension, diabetes or hepatitis C infection
- Have a low bodyweight
* HIV PrEP guidelines recommend investigating urine protein:creatinine ratio, but nephrology expert opinion is that this
test may miss early changes and albumin:creatinine ratio would be a more sensitive measure. A pragmatic approach is to start with a urine dipstick
and if protein is detected, request a urine protein:creatinine ratio, otherwise request an albumin:creatinine ratio.
Effective contraception should be provided to all people of child-bearing potential who are taking
PrEP and do not wish to become pregnant, including transgender males with female reproductive organs, if they have sex
with males.8 PrEP can be taken during pregnancy after balancing the risks and benefits of treatment; there
is an increased risk of HIV infection during pregnancy, but lower neonate bone mass density is a potential adverse effect.8
Renewing subsidised PrEP
To renew subsidised PrEP (required every three months) ALL of the following must apply:
- Applicant must have a current knowledge of safety issues and be competent to prescribe PrEP
- Patient must be confirmed HIV negative in the past two weeks and have had a full STI screen, including syphilis testing
- Renal testing (creatinine, phosphate, urine dipstick and albumin:creatinine ratio) in the past 12 months
- Patient must be advised on the risk of infection with STIs and how to reduce these risks, e.g. the correct and consistent use of condoms
AND the patient continues to meet ALL criteria of the initial Special
Authority application.
Testing before renewing PrEP
Follow-up consultations are necessary before renewing subsidised PrEP treatment. This needs to be carefully scheduled
as the patient must have a full STI screen, including HIV, syphilis, chlamydia and gonorrhoea in the two weeks prior to
applying for renewal of Special Authority approval (Table 2). The recommended testing regimen for
renewal of PrEP is:
- Blood tests for HIV and syphilis no more than two weeks before renewing the Special Authority
- Multi-site NAAT for chlamydia and gonorrhoea (urine, rectal, vulvovaginal and throat swabs as appropriate) within
two weeks of each renewal
- Serum creatinine, eGFR, serum phosphate, urine dipstick and albumin:creatinine ratio tests at first follow-up and every six months
thereafter; patients may require ongoing three-monthly testing
- Liver function test every 12 months, or more frequently if indicated‡
- Hepatitis C test every 12 months‡
- Pregnancy test in people of childbearing potential one month after initiation and every three months thereafter‡
‡ Not required for Special Authority approval
Table 2: Laboratory testing recommendations for initiation and follow-up of patients taking HIV PrEP8
| Investigation |
Baseline |
One month after initiation |
Every three months |
Additional frequency |
HIV and full STI screen* |
 |
|
|
– |
eGFR, phosphate, urine dipstick and albumin:creatinine ratio † |
|
– |
– |
At first follow-up and every six months thereafter ‡ |
Hepatitis A and B** |
|
– |
– |
– |
Hepatitis C |
|
– |
– |
At least every 12 months |
Full blood count |
|
– |
– |
– |
Liver function tests |
|
– |
– |
Every 12 months |
Pregnancy test for people of child-bearing potential |
|
|
|
– |
Required for Special Authority subsidy
Recommended
* Blood tests for HIV and syphilis and NAAT for chlamydia and gonorrhoea (urine, rectal swab, vulvovaginal swab, throat swab)
† More frequent monitoring may be appropriate for patients who are aged over 40 years or who have an
eGFR < 90 mL/min/1.73m2, or those with hypertension or
diabetes or who are taking non-steroidal anti-inflammatory drugs (NSAIDs) long-term
‡ Testing every 12 months is required for Special Authority renewal
** Ongoing testing for hepatitis B not necessary for immune patients unless there is an unexplained elevation in alanine aminotransferase
The adverse effects associated with PrEP are generally mild and transient. Gastrointestinal symptoms, e.g. nausea, vomiting,
abdominal pain, flatulence, diarrhoea, and headache are most frequently experienced.8 These are most likely
to be reported in the first month of treatment.8
There is an increased risk of hepatic adverse effects in patients with chronic hepatitis. The bone density of patients
taking PrEP may be reduced slightly and older patients with multiple risk factors for fractures, e.g. high alcohol consumption,
smoking, low body mass index (BMI), should be advised to reduce their alcohol intake, stop smoking, consume sufficient
calcium, ensure adequate exposure to sunlight to maintain vitamin D levels and perform weight-bearing exercises.8
Managing declining renal function
Initiation of PrEP is contraindicated in patients with an eGFR < 60 mL/min/1.73m2.8 However,
continued treatment may be possible if kidney function drops below this point, but only following discussion with a sexual
health or infectious diseases physician with expertise in PrEP or a nephrologist. Potential options include:8
- Permanently withdrawing treatment
- Pausing treatment for a brief period, e.g. one month, to allow renal function to recover (during which time they will
not be protected from HIV infection)
- Taking PrEP every second day (which might be less effective)
N.B. eGFR can be variable, e.g. due to the level of hydration, therefore, if testing indicates eGFR is < 60 mL/min/1.73m2 consider
repeating the test to confirm the result before withdrawing PrEP.
Interactions with other medicines and late-onset nephrotoxicity
Emtricitabine and tenofovir disoproxil predominately undergo renal excretion, therefore concurrent use of medicines
that are nephrotoxic or compete for active tubular secretion may cause serum levels to increase, e.g. valaciclovir, aminoglycosides
or long-term NSAIDs (including those purchased over-the-counter).8 Nephrotoxicity is rare in patients taking
PrEP, although proximal tubular dysfunction can occur, therefore monitoring of renal function every six months is recommended.8
Information about potential interactions between PrEP and other medicines is available on the New Zealand Formulary interaction
checker: www.nzf.org.nz/nzf_10222 . An interactions checker specific to HIV medicines is also available from the
University of Liverpool: www.hiv-druginteractions.org/checker
Encourage adherence to ensure ongoing protection
Patients should be educated about how PrEP works and understand that they will not be protected if they stop taking
it. Discuss the potential adverse effects, e.g. gastrointestinal disturbances, and provide reassurance that these usually
resolve within three months of initiating treatment. Recommend a routine for dosing, e.g. in the morning with toothbrushing,
and identify and address any barriers to adherence, e.g. substance abuse or mental illness. Adherence should be assessed
and encouraged at every consultation. If a dose is missed, advise the patient that they should take a tablet as soon as
they remember, unless there are fewer than 12 hours until the next dose, in which case the missed dose can be skipped.8
Patients taking fewer than four doses per week are unlikely to be protected against HIV infection and withdrawal of
treatment is recommended if a patient consistently reports taking less than this (see below).8
Patient information on HIV PrEP is available from:
www.nzaf.org.nz/assets/ee-uploads/files/Ending_HIV_PrEP_Booklet_WEB.pdf and
https://endinghiv.org.nz/stay-safe/prep
Reducing the patient’s risk of STIs
It is possible that some people may become complacent about STI prevention if they are taking PrEP. It is therefore
important to reinforce that PrEP only protects against HIV and to discuss:8
- Any barriers to consistent condom use
- Reducing any substance misuse
- Identifying one or two steps that the patient can take to reduce their STI risk
- Acknowledging efforts by the patient to reduce their risk and to reinforce these successes
Patient information on HIV, including links to other support organisations and resources, is available from:
www.nzaf.org.nz/living-with-hiv/
Withdrawing PrEP
Long-term treatment with PrEP may not be necessary for some patients, e.g. if they start consistently using condoms
or they enter a mutually monogamous relationship with a partner who is HIV-negative. It is recommended that patients wishing
to stop treatment continue taking PrEP for 28 days after their last potential exposure to HIV.8 Subsidised
PrEP can be reinitiated if the patient’s risk of HIV infection increases in the future. Record the patient’s HIV status,
reasons for discontinuing treatment, adherence while being treated and risk-taking behaviour.8 Any patient
with chronic hepatitis B infection should be discussed with a hepatologist or infectious diseases physician with expertise
in managing chronic HBV infection before withdrawing from PrEP, due to the risk of HBV reactivation.8
HIV Post-Exposure Prophylaxis (PEP)
Emtricitabine with tenofovir disoproxil is also a first-line option* in the emergency treatment (within 72 hours)
of a recent exposure to a potential source of HIV, including needle-stick injury, sexual assault or other high-risk
sexual exposure.16 A 28-day course of daily emtricitabine with tenofovir disoproxil, with or without an additional
antiretroviral, may be prescribed fully subsidised with Special Authority approval.16 Discussion with an
infectious diseases physician or referral to the local emergency department is recommended.
N.B. The Special Authority application for PEP can only be made by a named HIV specialist and uses a different form
than for PrEP.
* Not an approved indication for this medicine in New Zealand
A webinar on HIV PrEP for primary care presented by Dr Vincent Cornelisse and Dr Massimo Giola is available from:
https://www.goodfellowunit.org/events/hiv-prep-update-primary-care
