SOUTHERN.html
GUIDELINES
Southern
African guidelines for the safe use of pre-exposure prophylaxis in men
who have sex with men who are at risk for HIV infection
The Consensus Committee, Southern African HIV Clinicians Society, chaired by Linda-Gail Bekker and Kevin Rebe. MEMBERS:
Ben Brown, Peter Budnik, Glenn de Swardt, Zoe Duby, Nathan Geffen,
Brian Kanyemba, James McIntyre, Landon Myer, Andrew Scheibe, Laurie
Schowalter, Mark Sonderup, Wendy Spearman, Carlos Toledo, Tim Tucker,
Reon van Dyk, Gert van Zyl
Corresponding author:
A Scheibe (andrew.scheibe@gmail.com).
Background. The use
of oral antiretrovirals to prevent HIV infection among HIV-negative men
who have sex with men (MSM) has been shown to be safe and efficacious.
A large, randomised, placebo-controlled trial showed a 44% reduction in
the incidence of HIV infection among MSM receiving a daily oral
fixed-dose combination of tenofovir disoproxil fumarate and
emtricitabine (Truvada) in combination with an HIV prevention package.
Improved protection was seen with higher levels of adherence.
Aim. The purpose of this guideline is to: (i) explain what pre-exposure prophylaxis (PrEP) is; (ii) outline current indications for its use; (iii) outline steps for appropriate client selection; and (iv) provide guidance for monitoring and maintaining clients on PrEP.
Method. PrEP is indicated for HIV-negative
MSM who are assessed to be at high risk for HIV acquisition and who are
willing and motivated to use PrEP as part of a package of HIV
prevention services (including condoms, lubrication, sexually
transmitted infection (STI) management and risk reduction counselling).
Recommendations.
HIV testing, estimation of creatinine clearance and STI and hepatitis B
screening are recommended as baseline investigations. Daily oral
Truvada, along with adherence support, can then be prescribed for eligible MSM. PrEP should not be given to MSM with abnormal renal function, nor to clients who are unmotivated to
use PrEP as part of an HIV prevention package; nor should it be
commenced during an acute viral illness. Three-monthly follow-up visits
to assess tolerance, renal function, adherence and ongoing eligibility
is recommended. Six-monthly
STI screens and annual creatinine levels to estimate creatinine
clearance are recommended. Hepatitis B vaccination should be provided
to susceptible clients. Gastro-intestinal symptoms and weight loss are
common side-effects, mostly experienced for the first 4 - 8 weeks after
initiating PrEP. There is a
risk of the development of antiretroviral resistance among those with
undiagnosed acute HIV infection during PrEP initiation and among those
with sub-optimal adherence who become HIV infected while on PrEP.
Risk compensation (increasing sexual behaviours that can result in
exposure to HIV) while on PrEP may become a concern, and clinicians
should continue to support MSM clients to continue to use condoms,
condom-compatible lubrication and practice safer sex. Research is
ongoing to assess optimum dosing regimens, potential long-term effects
and alternative PrEP medications. Recommendations for the use of PrEP
among other at-risk individuals, and the components of these
recommendations, will be informed by future evidence.
S Afr J HIV Med 2012;13(2):40-55.
Men who have sex with men (MSM) is a term
that describes men who have sex with men, regardless of social identity
(gay, bisexual, heterosexual) or whether they also have sex with women.1 MSM have been shown to be at disproportionately high risk of HIV acquisition and transmission.2
,
3
Biological susceptibility (efficiency of rectal HIV transmission),
behaviours (including unprotected anal intercourse and multiple
partners) as well as structural and social factors (including
homophobia and discrimination) have been associated with increased
vulnerability to HIV.3 Unprotected receptive anal intercourse is the main risk factor for sexual transmission of HIV among MSM.4
The high concentration of rectal cells vulnerable to HIV-1 infection
(macrophages, T-cells and dendritic cells) and the single-cell layer of
rectal mucosa, results in a per-act risk for HIV transmission that is
10 - 20 times greater than unprotected vaginal intercourse.4
MSM and HIV in southern Africa
There is emerging and consistent evidence about the high HIV burden among MSM in southern Africa.7 HIV prevalence among MSM sampled in cross-sectional surveys in South Africa has ranged from 10 - 50%.8 However, owing to the lack of accurate population size estimates, it is hard to assess attributable risk.12
A 2009 modelling study on the modes of HIV transmission in South Africa
estimated that 8% of all new HIV infections in South Africa occur among
MSM.13 High-risk sexual
practices (including unprotected anal intercourse, multiple and
concurrent partnerships, and sex work) and limited knowledge about HIV
and substance use (alcohol, methamphetamines and heroin) have been
associated with increased risk for HIV infection among MSM in South
Africa.2
,
9
,
14 Many MSM
also have female sexual partners. Almost half (49%) of the participants
in a Soweto-based MSM study reported recent female sexual partners.10
Homophobia, stigma and discrimination (including criminalisation of
same-sex behaviours in some southern African countries), health care
worker ignorance (about MSM vulnerability to HIV and appropriate
management of MSM clients) and the heterosexual focus of the HIV
response have been contributing factors to the failure of southern
African public health services to address the health needs of MSM.2
,
12
,
17
The purpose of the MSM pre-exposure prophylaxis guideline is to:
• explain what pre-exposure prophylaxis (PrEP) is
• outline current indications for its use
• outline steps for appropriate client selection
• provide guidance to monitor and maintain clients using PrEP.
Pre-exposure prophylaxis
Pre-exposure prophylaxis (PrEP) is the taking of a
pharmaceutical agent prior to an exposure to prevent an outcome (e.g.
infection by a microbe). PrEP for HIV utilises antiretroviral
medications to prevent HIV infection. Research into the use of existing
and novel PrEP agents, topical (microbicide) and oral (tablet)
formulations is ongoing. In the Global iPrEx trial, PrEP was shown to
decrease HIV incidence among at-risk MSM (see text box).25
The results of this randomised placebo-controlled trial offer a new
opportunity for HIV prevention. Truvada, the oral antiretroviral agent
used in the iPrEx trial, is available for off-label use for PrEP in
South Africa.
Development of PrEP
Truvada (tenofovir disoproxil fumarate (TDF) in
combination with emtricitabine (FTC)) was chosen for the evaluation of
pre-exposure prophylaxis because of its high level of activity in
inhibiting HIV replication; its acceptable safety profile; its high
barrier to generating resistant virus; and its low levels of
side-effects.26 The protective activity of TDF and FTC has been shown in animal models, with best efficacy when both agents were used together.27
,
28
Several trials of daily oral TDF or TDF/FTC among heterosexual men and
women have recently been completed. Additional trials with heterosexual
women and injecting drug users are ongoing
(http://www.avac.org/ht/a/GetDocumentAction/i/3113). The findings of
the PrEP trials among heterosexual men and women have yielded differing
efficacy results, with some showing efficacy among heterosexual
sero-discordant couples receiving either TDF or TDF/FTC (Partners-PrEP)
and among young men and women (TDF2) receiving TDF/FTC. One PrEP trial
assessing the efficacy of daily oral TDF/FTC among women (FEM PrEP) was
stopped for reasons of futility (the inability to determine efficacy),
and the oral and topical tenofovir arms in the VOICE trial with women
were stopped for futility while assesment of efficacy of daily oral
TDF/FTC in the VOICE trial is continuing.29 Research is under way to assess reasons for these differing results.
The global iPrEx trial
The
global iPrEx trial was a double-blinded, randmised placebo-controlled
trial to assess the safety and efficacy of daily oral Truvada for the
prevention of HIV among MSM and transgender women. The subjects were 2
499 HIV-seronegative MSM or transgender women who have sex with men
enrolled from 11 sites in 6 countries. The Cape Town site was initiated
later than other sites, and only 88 MSM from South Africa were enrolled
(3.5% of total cohort) before the study was fully enrolled. All
subjects received monthly HIV testing, risk-reduction counselling,
condoms and management of STIs. The study subjects were followed for 3
324 person-years (median 1.2 years, maximum 2.8 years)(until 1 May
2010). Of the subjects, 10 were infected with HIV at enrollment (in
their ‘window’ period), and 100 became infected during follow-up (36 in
the Truvada group and 64 in the placebo group). In the modified
intent-to-treat analysis (excluding those who were infected at
enrolment and those with no follow-up HIV test results), an overall 44%
reduction in the incidence of HIV infection (95% confidence interval 15
- 63%; p=0.005)
among those randomised to Truvada use was seen. An as-treated analysis
showed that participants who reported taking the study drug at least
50% of the time, experienced 50% fewer infections. Participants who
reported taking 90% or more of their daily doses, experienced an
efficacy of 73%.25
Drug
levels were assessed in a case-control analysis of a subset of trial
participants. Each MSM who acquired HIV infection during the trial was
matched with two MSM who remained uninfected. No drug was detected in
participants in the placebo arm. Among participants in the Truvada arm,
drug was detected in 22 of 43 participants without HIV infection (51%)
and in 3 of 34 HIV-infected participants (9%) (p<0.001).25
Nausea
and unintentional weight loss were reported more frequently during the
first 4 weeks in the group receiving Truvada than in the placebo group (p<0.001). The two groups had similar rates of serious adverse events (p=0.57).25
Motivation for a MSM PrEP guideline
The iPrEx trial results contributed to the
development of interim guidance on the use of PrEP among MSM by the
United States Centers for Disease Control and Prevention.32
Based on the results of the iPrEx and Partners PrEP trials, a
submission to the United States’ Food and Drug Administration is
under consideration for expanding the indications for the use of
Truvada to include the prevention of sexual acquisition of HIV among
MSM and heterosexual adults. Truvada is not currently licensed for use
as PrEP in South Africa. Southern African guidelines will assist
practitioners who may be considering, or are already, prescribing PrEP
to at-risk MSM clients. This guideline is based on current evidence,
and future data will inform its revision and the potential extension of
indications to other population groups.
Initiation of PrEP
Steps for the screening, initiation and maintenance of PrEP for MSM are shown in Fig. 1.
1. Identification of potential PrEP users
Providers should educate and counsel MSM
clients about PrEP and conduct an individualised risk-benefit
assessment to assess eligibility.
Eligibility criteria for PrEP use include:
• men who have sex with men (MSM) (including those who also
have sex with women) who are identified by the provider and client as
being at high risk for HIV exposure (see text box on Indications for
the use of PrEP)
• no contra-indications to Truvada (FTC/TDF)
• HIV-negative by routine rapid antibody test
• absence of symptoms of acute HIV infection (recent acute
viral illness) and, if symptoms reported, HIV-negative by
4th-generation HIV test or other HIV antigen test if available (this
reduces, but doesn’t eliminate, the window period)
• motivated to follow PrEP prescribing guidelines
• willing and able to adhere to daily oral dosing†
• willing and able to
attend 3-monthly PrEP maintenance visits, inclusive of HIV counselling
and testing, clinical review and safety monitoring procedures
• client understanding that the protection provided by PrEP is
not complete, and of the need for PrEP to be used as part of a package
of HIV prevention services (inclusive of condoms, lubrication, risk
reduction counselling and STI management)
2. Baseline investigations
After documenting eligibility and motivation
for PrEP use, mandatory baseline investigations should be completed
(Table 1). If resources permit, a DEXA scan to measure bone mineral
density among individuals who report a history of pathologic fracture
or a family history of osteoporosis should be considered.
Unavailability or inability to cover the costs of a DEXA scan should
not preclude PrEP use. Condoms and condom-compatible lubrication should
be provided, and arrangements for follow-up made.
Indications for the use of PrEP
PrEP may be suitable for MSM who:
• engage in anal sex and are HIV uninfected
• are at high risk for HIV acquisition
• MSM with multiple partners
• MSM engaging in transactional sex, including sex workers
• MSM who use or abuse drugs
• MSM who drink alcohol heavily
• More than 1 episode of a STI in the last year
• Couples‡
• HIV-negative partner in a
discordant relationship, especially if the positive partner is not on
antiretroviral therapy (ART)
• Both partners HIV negative in a non-monogamous concordant relationship
• MSM who are unable or unwilling to achieve consistent use of male condoms
• are motivated, able and willing to adhere to daily oral dosing.
Contraindications for PrEP:
HIV-1 infected or evidence of possible acute HIV infection
• allergy to tenofovir disoproxil fumarate and/or emtricitabine
• poor renal function (estimated creatinine clearance <60ml/min)
• unwilling or unable to return for 3-monthly HIV testing, counselling and safety monitoring visits.
3. Implementing PrEP
At the follow-up visit, repeat the rapid HIV test
and do a review for acute viral symptoms. Review results from baseline
investigations and confirm that estimated creatinine clearance >60
ml/min. Commence hepatitis B vaccination if susceptible and provide STI
treatment as required (Table 2). Educate the client about potential
PrEP side-effects and their management, as well as signs and symptoms
of acute HIV infection (and need to return for ‘urgent’ HIV
testing). Initiate a medication adherence plan and provide a 1-month
Truvada prescription (1 tablet orally, daily) together with a 1-month
follow-up date (Table 3).
Risk-reduction counselling
Risk-reduction counselling is a behavioural
intervention that attempts to decrease an individual’s chances of
acquiring HIV and other STIs,33
and should be implemented together with adherence counselling at
follow-up visits for clients using PrEP. The main objective of
risk-reduction counselling is for clients to set a realistic goal for
behaviour change that could reduce their risk of contracting HIV. This
is most effective when it is non-prejudicial and client-centred. Risk
reduction counselling can be provided by any trained healthcare
provider and should address the following points:
1. Explore the context of the user’s specific sexual
practices, and assist client to recognise which of their behaviours are
associated with higher risks for HIV infection. Clinicians should also
be aware that clients may not always perceive their own risk, or be in
denial about it.
2. Identify the sexual health protection needs of the user and reflect on what their main concerns appear to be.
3. Strategise with the user on how they can manage these concerns or needs.
4. Agree on which strategies the user is willing to explore and guide the user to decide on how to implement the strategy.
Adherence support
Adherence to daily PrEP medication, as shown in the
iPrEx study and other PrEP trials, is a challenge. Adherence
counselling should be implemented at each visit where PrEP
prescriptions or distributions are made. In iPrEx, MSM who took PrEP
more consistently and had evidence of drug detection in their blood,
had higher levels of protection than those who did not.25
Clients will need to be made aware of the fact that drugs only work
if present at adequate levels in tissues and, preferably, drug levels
should be adequate before and after exposure to HIV has occurred.
The use of cell phone reminders, pill boxes, and linking pill
taking with a daily routine activity are currently being evaluated for
their impact on improving PrEP adherence. Clinicians and clients could
use any of these or other strategies to assist in maximising adherence
(see text box on Tips to Support Adherence). Any trained healthcare
worker can implement adherence counselling. A client-centred approach
is recommended. Drug level testing for tenofovir levels in plasma is
available, but is expensive. Drug level testing may be useful to assess
adherence in the future.
Tips to support adherence
Include
patient-focused adherence counselling at each contact. Provide a clear
explanation of the benefits of adherence. In a neutral manner, ask if
the client has any challenges that may make adherence difficult. Also
explore possible facilitators to pill taking. Include identified
facilitators when developing strategies to improve adherence.34
Options to improve daily pill taking:
• use reminders (cell phone, alarm clock, diary, partner reminder)
• link with daily activity (breakfast, brushing teeth)
• use of a pill box.
Strategies to reduce likelihood of antiretroviral resistance
Feasibly exclude acute HIV infection before initiating PrEP by:
• conducting antibody HIV testing before commencing or represcribing PrEP
•
among persons with a negative antibody HIV test, conduct a clinical
screen to detect signs and symptoms of acute HIV infection – history of
fever, sore throat, rash, joint pain, cough in the past month and a
targeted examination (temperature, ENT and skin exam)(see Acute HIV
infection text box)
• If symptoms or signs of acute HIV infection found:
• at screening: postpone PrEP until symptoms subside and rapid antibody test remains negative
• at screening: do not initiate PrEP until confirmatory HIV antigen/antibody testing complete*
•
at follow-up: may elect to continue PrEP while awaiting results of
confirmatory HIV antigen/antibody testing or may decide to withhold
PrEP until confirmatory tests available
• support client to maximise adherence and include adherence counselling at each visit
• stop PrEP should requirements for PrEP eligibility not be fulfilled.
Managing abnormal screening results
Clients with abnormal renal function (estimated
creatinine clearance <60 ml/min) should not be placed on PrEP. An
abnormal estimated creatinine clearance result could be rechecked after
2 weeks and, if renal function returns to normal and other PrEP
criteria are met, PrEP may be initiated. MSM who are susceptible to
hepatitis B should be immunised.* Clients with a history of
pathological bone fracture, a family history of osteoporosis, or
decreased bone mineral density on DEXA scanning, should be educated on
ways to improve bone health, such as weight-bearing exercise,
maintaining adequate calcium and vitamin D intake, and avoiding
alcohol, tobacco and recreational drugs.35
MSM who are ineligible for PrEP require support to assess other
prevention options (see HIV Prevention for MSM text box). Treat STIs
syndromically as per national guidelines (Table 2).36
MSM who test HIV positive should be clinically staged, have a CD4 count
taken and be managed in line with HIV treatment guidelines
(http://www.sahivsoc.org/practise-guidelines/national-dept-of-health-guidelines).
Safety monitoring and maintenance
MSM using PrEP require an initial 1-month follow-up
to assess ongoing eligibility, tolerance, safety and adherence.
Hepatitis B vaccination and STI treatment (as appropriate), condoms and
condom-compatible lubricant, risk reduction counselling, adherence
support, a 3-month prescription for Truvada and a follow-up date should
be provided. Thereafter, 3-monthly visits are recommended (Table 3).
Details on recommended monitoring of bone mineral density is provided
under Other notes for PrEP prescribers below.
Managing abnormal follow-up visit results
PrEP should be stopped if estimated creatinine
clearance <60 ml/min. Repeat creatinine clearance should be
rechecked after 2 weeks; if renal function returns to normal and other
PrEP criteria are met, PrEP may be restarted.
STIs should be treated syndromically (Table 2).
By mutual agreement, PrEP should be stopped if: HIV test is
positive; the client no longer meets eligibility criteria; the client
and provider feel that adherence to PrEP is too onerous; or it is
perceived by the clinician that the risks of PrEP outweigh potential
benefits.
MSM who are ineligible for PrEP require support to access other prevention options (see HIV prevention for MSM text box below).
Risks and side-effects
Antiretroviral resistance
The only HIV resistance documented to date among
PrEP users has been among clients who started using PrEP when they were
already HIV-infected (during acute HIV infection). Predictably, FTC
resistance mutations were the first to occur.25 To prevent the risks of ARV resistance, clinicians must focus on not providing PrEP during acute HIV infection.
HIV testing should be done
3-monthly, and should be accompanied by a symptom screen and a targeted
examination to exclude acute HIV infection (see text box on Acute HIV infection).
HIV testing should also be repeated whenever symptoms of a viral
illness are present. Clinicians should advise clients on the need for
an HIV test before resuming PrEP if it was stopped, particularly if
they have potentially been exposed to HIV during this period.
Side-effects
Most available Truvada safety data are derived from studies of HIV positive individuals receiving ART.26 Safety data of Truvada use in HIV-negative individuals are emerging from PrEP trials and are reassuring.25
Gastro-intestinal side-effects
The side-effects related to Truvada use in PrEP
trials (nausea, weight loss) were mostly self-limiting start-up
symptoms (first month), but these may adversely affect PrEP adherence.
Supportive counseling and symptomatic treatment (anti-emetics) of these
symptoms are often sufficient. Rates of other GIT symptoms (bloating,
abdominal tenderness, flatulence) among PrEP trial participants who
took Truvada were not significantly different from those who took
placebo.25
Acute HIV infection
Severity
of the syndrome ranges from mild non-specific ‘viral’ or ‘flu-like’
symptoms to a severe infectious mononucleosis like illness with immune
dysregulation and transient profound CD4 depletion.37
,
38
Potential predictable side-effects
Major side-effects: renal toxicity and metabolic complications (decreased bone mineral density)
Minor side-effects:
gastrointestinal symptoms (diarrhoea, nausea, vomiting and flatulence),
unintentional weight loss and a small risk of lactic acidosis and
hepatic steatosis or steatohepatitis
Less predictable side-effects:
may include hypersensitivity reactions and flares of hepatitis B in
clients who are chronic carriers who receive and then stop tenofovir,
lamivudine or emtricitabine
Renal toxicity
Modest, transient increases in serum creatinine
have been noted in completed PrEP studies, but these did not persist
after stopping PrEP nor recur on rechallenge. Proteinuria, decreasing
glomerular filtration rate (GFR) and Fanconi’s syndrome* have
been described in the setting of ART, and decreased GFR has been
described in the setting of PrEP but has either been statistically or
clinically insignificant.25
Renal function needs to be
measured prior to commencement and monitored in clients using PrEP by
measuring serum creatinine and calculating the estimated creatinine
clearance. These parameters should be measured at baseline, at month 1,
month 4 and then annually thereafter. Hypertensives, diabetics, and
those with existing glomerulonephropathies (if the benefit of PrEP is
still deemed to outweigh clinical risk) should have monthly renal
function checks. Truvada-based PrEP should be avoided in patients who
require the use of other nephrotoxic drugs such as aminoglycosides for
the treatment of drug-resistant tuberculosis (TB). Clients with
creatinine clearance <60 ml/min should not be placed on PrEP and, if found during maintenance, PrEP should be discontinued.
Decreased bone mineral density
Decreases in bone mineral density associated with
TDF and FTC/TDF have been observed in completed PrEP trials. Decreases
were less than those observed in HIV-infected individuals treated with
the same drugs, and appeared to stabilise over time.39
,
40
No difference in fracture rates were seen. Recreational drugs
(amphetamines and inhalant use) were associated with reductions in bone
mineral density in HIV-negative MSM taking TDF while enrolled in a PrEP
study.39
Hepatitis B management
Tenofovir and emtricitabine both have hepatitis B
antiviral activity. The risk exists that exposure to these antivirals
may treat unidentified chronic hepatitis B infection with a consequent
viral flare (rebound) upon drug withdrawal that can result in a severe
liver injury.41 It is
recommended that screening for hepatitis B surface antigen and
antibodies occurs prior to PrEP commencement. It is recommended that,
if hepatitis B surface antigen (HBsAg) is positive, the client be
referred for assessment prior to commencement of – in particular
– short-term PrEP (Table 4). A possible approach to those with
chronic hepatitis B infection may be to prescribe long-term
tenofovir/emtricitabine. Liver function tests should be checked after
stopping PrEP in those with chronic hepatitis B infection. Clients who
are negative for both HBsAg and hepatitis B surface antibody (HBsAb)
should commence a hepatitis B vaccine schedule. Clients with a history
of injecting drug use should be screened for hepatitis C and, if
positive, referred for further care.
Risk compensation
This is the theoretical risk that individuals
commencing PrEP will neglect other safer-sex measures, and put
themselves at increased risk of HIV exposure. To date, no PrEP trials
have borne out evidence in support of this risk. Providers should gauge
this during risk reduction and adherence counselling opportunities.
HIV prevention package for MSM
The prevention of HIV acquisition requires a
comprehensive approach, inclusive of a combination of biomedical and
behavioural/ psychosocial interventions tailored to individual needs.
Where feasible, condoms and condom-compatible lubrication are key
components of all HIV prevention packages, supported by STI detection
and treatment, appropriate use of ART (post-exposure prophylaxis), and
counselling around the identification of high-risk practices and ways
to circumvent or reduce risk.
Stopping PrEP
PrEP should be stopped: whenever an HIV test is
positive; at client request; for safety concerns (particularly if
creatinine clearance <60 ml/min); and if the risks of PrEP outweigh
the potential benefits. Linkage to appropriate HIV services should be
arranged, and use of other HIV prevention strategies used, as needed.
The duration of PrEP use may vary and individuals are likely to
start and stop PrEP depending on their risk assessment at different
periods in their lives – including changes in relationship
status, behaviours and ability to adhere to a PrEP maintenance
programme. Clients should be advised that an HIV test should be done
before PrEP is recommenced. Clinicians may want to discuss the options
of when to discontinue PrEP with their clients.
Other notes for PrEP prescribers
PrEP will not suit all users.
PrEP should be considered for MSM clients who are most likely to
benefit from this specific prevention strategy as part of a package of
HIV prevention services.
PrEP usage requires commitment.
Usage will require commitment from both the provider and the user to
ensure success. A paradox is that MSM clients who are most likely to
benefit from PrEP because they are at the highest risk of exposure to
HIV may find adherence to a programme particularly challenging.
Providers may need to be innovative in providing support to these users.
Monitoring of bone mineral density.
Based on current evidence and expert opinion, and where feasible,
baseline DEXA scans should be done in clients with a family history of
osteoporosis and/or a pathological fracture. Importantly, the
unavailability of DEXA should not preclude PrEP use. Annual follow-up
DEXA scanning is suggested (Table 5). Ongoing research on the role of
DEXA scanning will inform future recommendations.
HIV prevention for MSM
• accessibility of condoms and compatible water-based lubricant should be addressed
• no single HIV-risk reduction intervention is likely to suit all MSM
•
combinations of prevention options, tailored to address specific risks,
should be offered (‘menu of prevention choices’), inclusive of
biomedical and psychosocial/behaviour change interventions
• prevention options are likely to increase as new evidence becomes available.
Drug-drug interactions
Tenofovir
should not be co-administered with adefovir. Other drugs listed below
can be co-administered but may require close monitoring, alteration of
dosage or timing of administration.
Common drugs which may interact with emtricitabine (FTC) or tenofovir (TDF)
Drug name
FTC
TDF
Adefovir
X – do not co-administer
Cimetidine
X
Digoxin
X
X
Furosemide
X
X
Metformin
X
X
Naproxen
X
X
Ofloxacin
X
X
Streptomycin
X
X
Sulfadoxine/pyrimethamine
X
X
Source:
University of Liverpool. Interactions with NRTIs, October 2011
(http://www.hiv-druginteractions.org/data/PrintableCharts/NRTI_col.pdf).
PrEP: What we don’t yet know
• What is the long-term efficacy of PrEP for MSM?
• What is the effect of PrEP on sexual behaviour and HIV risk?
•
What are the long-term effects of tenofovir/emtricitabine on renal
function, bone mineral density, chronic viral hepatitis B and other
effects in HIV-negative MSM?
• Will resistance be a common event among those infected while using PrEP?
• What is the ideal PrEP regimen and dosing interval?
• What are the predictors of adherence for MSM who use PrEP?
• Which MSM are most likely to benefit from PrEP?
• What will be the role of PrEP among sero-discordant MSM couples?
• What will be the long-term effect on treatment programmes that share ART medications with PrEP programs?
The future of PrEP
Many questions surrounding the safe and effective use of PrEP exist; ongoing research aims to address these knowledge gaps (PrEP:
What we don’t yet know text box above).
The iPrEx open-label extension study, and other similar studies, are
trying to increase our understanding around long-term PrEP usage
(http://iPrExole.com/) specifically for MSM. Health facilities and
health workers may be able to help answer these questions by keeping
careful records of side-effects, patient adherence reports and HIV and
hepatitis infections in their clients taking PrEP. Adverse events can
be reported to the National Adverse Drug Event Monitoring Centre which
is housed in the Division of Pharmacology at the University of Cape
Town. The reporting guideline is available at:
http://www.mccza.com/genericDocuments/2.11_ADR_reporting_Jun11_v2.doc.
EXTERNAL REVIEWERS: Stefan Baral, Chris Beyrer, Robert Grant, Al Liu, Kathy Muligan, Tim Lane, Dawn Smith.
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†Therapeutic
drug monitoring is currently not routine, although methods that require
less invasive procedures, such as measuring drug levels in hair, are
being validated.
‡Couples in this instance refers to men who have had sex with each other more than once.
Fig. 1. Flowchart for the screening, initiation and maintenance of PrEP among MSM.
*Use 4th-generation HIV rapid (antigen+antibody) tests where available to confirm HIV infection status.
Table 1. Mandatory baseline investigations for PrEP initiation among MSM
HIV infection
Rapid HIV antibody test
Renal function
Estimated creatinine clearance (ml/min)
(formula for males) (140 - age in years) x weight (kg)
0.82 x plasma creatinine (µmol/l)
Hepatitis B screen
Surface antigen (HBsAg)
Antibody to surface antigen (HBsAb)
STI screen
Symptomatic screen
Examination if indicated
Urine dipstix for urethritis
Serological screening for syphilis (rapid or laboratory)
Table 2. Syndromic treatment of STIs among MSM
Urethritis
Cefixime 400 mg PO stat, plus doxycycline 100 mg PO 12-hourly for 7 days.
If symptoms persist after 7 days and repeat exposure and poor adherence are excluded, give metronidazole 2g PO stat.
If still symptomatic after a further 7 days, refer.
Genital ulcers
Benzathine penicillin 2.4 million units IM stat for
primary syphilis (repeat benzathine penicillin x 2, at weekly intervals
for late syphilis), plus erythromycin 500 mg PO 6-hourly for 7 days and acyclovir 400 mg PO 8-hourly for 7 days
Rectal discharge/proctitis
Cefixime 400 mg PO stat (or ceftriaxone 250mg IMI stat) plus
doxycycline 100 mg 12-hourly for 7 days (also screen for syphilis and
consider acyclovir if any suggestion of ulcerative anal disease).
Table 3. Summary of PrEP visits and procedures
Visit
Recommended procedures
Screening visit
Educate about the risks and benefits of PrEP
Assess eligibility and motivation
Conduct HIV counselling and testing, serum creatinine level and STI and hepatitis screen
Arrange follow-up
PrEP initiation visit
Conduct HIV counselling and testing
Confirm eligibility (including investigation results and a calculation of creatinine clearance)
Commence hepatitis B immunisation (if indicated)
Provide STI treatment (if indicated)
Educate client about PrEP side effects and their management
Educate client about signs and symptoms of acute HIV infection
Discuss behaviours that promote bone health, such as
weight-bearing exercise, maintaining adequate calcium and vitamin D
intake, and avoiding alcohol, tobacco and recreational drugs
Initiate a medication adherence plan
Provide condoms and lubricant
Provide 1-month Truvada prescription and 1-month follow-up date
1-month follow-up
Same as PrEP initiation visit, plus:
assess tolerability, side-effects and adherence
measure serum creatinine and calculate creatinine clearance
provide 3-month Truvada prescription and follow-up date
4-month follow-up and maintenance
Repeat procedures done at 1-month follow-up
Measure serum creatinine and calculate creatinine clearance at 4-month follow-up, and annually thereafter
Conduct 6-monthly STI screen for urethritis, genital ulcers and proctitis, including urine dipstix and rapid syphilis test
Complete hepatitis B immunisation
*Hepatitis B
immunisations could be provided at PrEP initiation and at 1-month and
7-month follow-up visits. This schedule differs from standard
vaccination at months 0, 1 and 6, but would minimise additional visits.
*Fanconi’s
syndrome consists of renal tubular acidosis, hypophosphataemia,
hypouricaemia together with urinary losses of glucose, amino acids and
protein sometimes coupled with a reduced glomerular filtration rate.
Symptom
Sign
Malaise
Anorexia
Myalgias
Headache
Sore throat
Sore glands
Fever, sweating
Generalised lymphadenopathy
Hepatospenomegaly
Non-exudative pharyngitis
Aphthous ulceration
Truncal rash (maculopapular or urticarial)
Viral meningitis
Guillian-Barre syndrome
Pneumocystis pneumonia
Cryptococcal meningitis
Oesophageal candidiasis
Table 4. Hepatitis B immune status and eligbility for PrEP
Hepatits B surface antigen (HBsAg)
Hepatitis B surface antibody (HBsAb)
Action
negative (-)
negative (-)
Start PrEP, vaccinate concurrently
negative (-)
positive (+)
Start PrEP, no vaccine needed
positive (+)
N/A
Refer for evaluation
Biomedical
Psychosocial
Male condoms and compatible lubrication
Regular HIV counselling and screening
Early access to ART
Reducing number of sex partners
Post-exposure prophylaxis (PEP)
Reducing alcohol and substance abuse
Pre-exposure prophylaxis (PrEP)
Addressing mental health needs
STI screening and treatment
Couples counselling and programming
Needle syringe exchange and opioid substitution therapy for MSM who inject drugs
Harm reduction counselling and support for drug using MSM
Table 5. Monitoring bone mineral density (DEXA scan) among MSM using PrEP
HIV acquisition risk
Osteopaenia risk
Resources
Intervention
High
High
High
PrEP + DEXA scan (baseline and 12-monthly)
Moderate
High
High
PrEP + DEXA scan (baseline and 12-monthly)
High
High
Low
PrEP + advise and observe
Moderate
Low
Low
PrEP + advise and observe
High
Low
High
PrEP + DEXA scan (baseline, repeat if indicated)
High
Low
Low
PrEP + observe