2020 Southern African HIV PrEP Guidelines PDF

Southern African Journal of HIV Medicine ISSN: (Online) 2078-6751, (Print) 1608-9693 Page 1 of 8 Guideline Southern African guidelines on the safe, easy and effective use of pre-exposure prophylaxis:...

Southern African Journal of HIV Medicine ISSN: (Online) 2078-6751, (Print) 1608-9693 Page 1 of 8 Guideline Southern African guidelines on the safe, easy and effective use of pre-exposure prophylaxis: 2020 Authors: Introduction Linda-Gail Bekker1 Benjamin Brown2 Pre-exposure prophylaxis (PrEP) with antiretroviral agents to prevent human immunodeficiency Dvora Joseph-Davey3,4 virus (HIV) acquisition is now a standard of care in many countries. After more than a decade of Kathrine Gill1 research and dozens of randomised trials, it is clear that PrEP is both safe and efficacious. Oral Michelle Moorhouse5 Sinead Delany-Moretlwe5 PrEP is thus a key component of an HIV prevention package and should be offered to anyone Landon Myer4 who may be exposed to HIV, whether sexually or through other means. With the highest HIV Catherine Orrell1,6 incidence in the world, PrEP use in the South African population remains unacceptably low and Kevin Rebe7,8 W.D. Francois Venter9 insufficient to reach its full impact as an HIV control measure. To realise the full value of this Carole L. Wallis10 prevention tool, PrEP must become more accessible. Therefore, the updated 2020 PrEP guidelines have (1) broadened eligible groups to include pregnant and breastfeeding women, (2) reduced Affiliations: 1 Desmond Tutu HIV Centre, clinical and health system barriers to simplify PrEP initiation and administration (e.g. same-day Institute of Infectious Disease PrEP), (3) broadened PrEP delivery to include on-demand PrEP in men who have sex with men and Molecular Medicine, and transgender women, (4) provided updates of adverse events and relevant drug–drug University of Cape Town, interactions and (5) suggested parameters with which to measure PrEP rollout and success. Cape Town, South Africa 2 Anova Health Institute, Johannesburg, South Africa Background The first Southern African HIV Clinicians Society pre-exposure prophylaxis (PrEP) guidelines 3 Department of Epidemiology, were published in the Southern African Journal of HIV Medicine in 2012 following labelling University of California, Los approval by the Federal Drug Administration (FDA) in the United States of America.1 The Angeles, United States of America results of three clinical trials underpinned those guidelines: the Global iPrEx study in men who have sex with men (MSM) and transgender (TG) people, the Partners PrEP study in discordant 4 Division of Epidemiology and couples in Uganda and Kenya and the tenofovir disoproxil fumarate (TDF) 2 study in Biostatistics, School of Public Health and Family Medicine, heterosexual men and women from Botswana.2,3,4,5 Since then a further seven randomised University of Cape Town, controlled trials (RCTs) and numerous open label demonstration studies have led to the Cape Town, South Africa registration of combination therapy, with tenofovir and emtricitabine or related variations thereof as effective tools in the prevention of human immunodeficiency virus (HIV) transmission 5 Wits Reproductive Health and HIV Research Unit, University to uninfected persons.6,7,8,9,10,11,12,13,14,15,16,17,18,19 The World Health Organization (WHO) set a target of the Witwatersrand, of 3 million PrEP users worldwide by 2020. With 240 000 incident HIV infections per year in Johannesburg, South Africa South Africa, which is equivalent to almost 15% of all new infections globally,20 a significant portion of those effective PrEP users should be in this country. However, despite the research, 6 Department of Medicine, University of Cape Town, demonstration projects and existing guidelines, PrEP use remains low and insufficient to Cape Town, South Africa effectively reduce South African HIV incidence rates, with only an estimated 45 000 people using PrEP as of June 2020.21 7 Life Vincent Pallotti Hospital, Cape Town, South Africa People who have been offered PrEP and have integrated it into their daily lives describe how they 8 Department of Medicine have felt more in control of their circumstances, more free of worry and able to once again enjoy and Infectious Diseases, their sexual intimacies in ways that have not been possible for decades given South Africa’s very University of Cape Town, Cape Town, South Africa high HIV prevalence. In foreign cities such as London and San Francisco and regions such as New South Wales in Australia where universal test and treat strategies have been coupled with extensive scale-up for PrEP, the rates of new HIV infections have dropped precipitously.22 It is expected that with the assistance of these guidelines, further PrEP scale-up will soon be possible in South Africa with similar positive outcomes. 9 Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Read online: 10 BARC-SA, Speciality Molecular Division, Lancet Laboratories, Johannesburg, South Africa Scan this QR Corresponding author: Linda-Gail Bekker, [email protected] code with your Dates: Received: 14 Aug. 2020|Accepted: 14 Aug. 2020|Published: 10 Dec. 2020 smart phone or mobile device How to cite this article: Bekker L-G, Brown B, Joseph-Davey D, et al. Southern African guidelines on the safe, easy and effective use of to read online. pre-exposure prophylaxis: 2020. S Afr J HIV Med. 2020;21(1), a1152. https://doi.org/10.4102/sajhivmed.v21i1.1152 Copyright: © 2020. The Authors. Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License. http://www.sajhivmed.org.za Open Access  Page 2 of 8 Guideline The 2012 PrEP guideline was last updated in 2016. Whilst TDF/FTC is available for all populations, TAF/FTC The current (2020) guideline provides further options has so far only been shown to be efficacious in men and TG regarding drug use and the practice of oral PrEP,1 including women. Studies in cisgender women are planned. (1) broadened eligible groups to include pregnant and Pre-exposure prophylaxis at this time is in the form of breastfeeding women, (2) reduced clinical and health oral pills only, but topical rings and long-acting injectables system barriers to simplify PrEP initiation and are under investigation.27 administration (e.g. same-day PrEP), (3) broadened PrEP delivery to include on-demand PrEP in MSM and TG women, (4) provided updates of adverse events and relevant Who is pre-exposure prophylaxis for? drug–drug interactions and (5) suggested parameters with Pre-exposure prophylaxis is an effective prevention option which to measure PrEP rollout and success. We also for any sexually active person who might be exposed to HIV introduce alternative oral antiretroviral (ARV) agents and through contact with HIV-infected body fluids (genital and new modalities on the horizon. We present an updated blood). Pre-exposure prophylaxis is suitable for people of lexicon for PrEP clients and users in Figure 1. any sex, gender and sexual orientation. Quick facts on oral pre-exposure The WHO recommends that PrEP should be scaled up for prophylaxis populations where the incidence of HIV is 3% or greater.24 Although risk is unevenly distributed across sub- At this time, PrEP is the daily use by the HIV-uninfected of oral populations and geographic areas in Southern Africa, a TDF or tenofovir alafenamide (TAF)/Emtricitabine (FTC) very large number of sexually active people are exposed to co-formulated with emtricitabine (TDF/FTC or F/TAF) or this degree of risk. Whilst many PrEP efforts have focused variations of this, for example, TDF on its own on specific ‘high-risk’ or key population groups, at an or co-administered with lamivudine (3TC) to prevent individual client level, anyone who reports that he or she is HIV acquisition (transmission). The most commonly used at risk of HIV infection might benefit from PrEP. In these preparation and the one licensed in South Africa for oral PrEP is TDF/FTC. Pre-exposure prophylaxis has been shown to be cases, PrEP education should be provided and intervention effective amongst a wide range of HIV-negative populations. should be offered. There are other drugs and other routes of administration under investigation, for example, a topical dapivirine vaginal On the contrary, the use of a risk scoring tool is not ring and long-acting injectable cabotegravir. The registration recommended but rather that an accurate sexual history is of TAF is currently under review in South Africa. These elicited from clients to identify sexual behaviours that justify guidelines will be updated as new data become available21: consideration of improved or enhanced HIV prevention strategies. This is because risk scores fail when risk is not well Pre-exposure prophylaxis has a long history of effectiveness in the setting of preventing vertical HIV judged and individual risk levels are dynamic; in addition, transmission. Protective in utero foetal ARV drug levels no single risk score has been validated for generalised use. are optimised prior to delivery (exposure).23 Given the high ongoing rates of HIV transmission in South Consistent adherence to PrEP reduces the risk of HIV Africa and low current PrEP demand and no saturation in transmission from sex by > 95%.2 both the private and public sectors,21 people seeking PrEP For those at risk, daily PrEP has been confirmed to be should be encouraged to initiate PrEP, provided that they are effective in the prevention of sexual and injecting drug sexually active and there is a reasonable risk that they might use HIV transmission. Where adherence is suboptimal, be exposed to HIV (see Table 1). PrEP is less effective (unreliable) as protective drug (ARV) levels at the time and site of exposure may be too low. Differing pharmacokinetic (PK) data play a role in different Daily use is the most dependable way to ensure recommendations for dose frequency in different populations. effectiveness.24 Tissue drug concentrations in genital and anal mucosa vary Condom use is still recommended as PrEP does not with higher levels and steady states reached more rapidly in protect against other sexually transmitted infections anal compared with vaginal mucosa.28 Pharmacokinetic (STIs), such as syphilis, chlamydia and gonorrhoea. modelling studies have suggested that fewer doses may be Pre-exposure prophylaxis has no contraceptive effect. required to reach effective concentrations in anal compared The drugs used in PrEP do NOT interact with with vaginal mucosa. This has led to three recommendations hormonal contraception. that depend on whether exposure is via vaginal (heterosexual Pre-exposure prophylaxis is safe to take when pregnant sex) or anal mucosal routes: or breastfeeding.19,25 On-demand PrEP (for MSM and TG women only): Two Pre-exposure prophylaxis where the HIV exposure is via pills are taken 2–24 h before sex. If sex occurs, the vaginal mucosa should be dosed daily. individual who is or is presumed to be HIV-uninfected Pre-exposure prophylaxis where the HIV exposure is via follows up with one pill per day for 2 days after sex.26 vaginal mucosa may require up to 7 days of dosing before Pre-exposure prophylaxis is generally well tolerated. being fully effective. Occasional side effects include nausea, bloating and/or On-demand PrEP is not recommended where exposure is headaches in approximately one in 10 users. via vaginal mucosa. http://www.sajhivmed.org.za Open Access  Page 3 of 8 Guideline TABLE 1: Populations for pre-exposure prophylaxis consideration. Population Risk group Special considerations Adolescents Any/all Must weigh > 35 kg. Should be allowed to consent independently but support is advisable especially to assist with persistence. Women Mostly vaginal sex but may also engage Pre-exposure prophylaxis (PrEP) is highly efficacious when dosed daily in HIV-uninfected women. It is a in oral† and anal sex user-dependent, discreet addition to the prevention menu for women. When providing PrEP to women, it is important to provide it in the context of other health interventions.27,28,29 Considerations such as pap smears, contraception, breastfeeding and post-partum care should be covered. However, access to these is not a prerequisite to prescribing PrEP. Men Penile and oral Pre-exposure prophylaxis works for men who are HIV-negative and at risk of HIV acquisition. Men who have sex Penile, anal and oral Tissue concentrations of TDF/FTC appear to be higher at the anal mucosa and are reached more rapidly in with men (MSM) the anal mucosa than in vaginal mucosa. It has been demonstrated in modelling studies that four doses per week may be sufficient to safely protect MSM. Recent trials have also confirmed that on-demand PrEP is efficacious.28 Pregnant and Primarily vaginal sex but may also Pre-exposure prophylaxis is safe in pregnancy and during lactation. There are no contraindications of breastfeeding women engage in anal and oral sex taking PrEP during pregnancy and breastfeeding.19,25 HIV incidence is high during pregnancy and breastfeeding, with HIV acquisition risk more than double during pregnancy and the postpartum period compared to when women are not pregnant.30 Pre-exposure prophylaxis counselling should be provided to all HIV-negative pregnant women at risk of HIV. Pre-exposure prophylaxis provision and risk reduction counselling should be aligned with antenatal and postnatal visits. Symptoms such as nausea and gastrointestinal symptoms are far more common and more severe than with PrEP, especially in the first trimester, and should thus be actively managed. There are no data yet on TAF/FTC in pregnancy. Serodiscordant couples A partner has unknown or HIV-positive Pre-exposure prophylaxis may be used as a ‘bridge’ until the partner living with HIV has an undetectable status and is not virally suppressed viral load – at that point PrEP may be discontinued depending on the preference of the couple.31 Safer conception Serodiscordant couples wishing Pre-exposure prophylaxis may be provided to the HIV-negative partner during condomless sex whilst trying to conceive to conceive, and whilst pregnant and breastfeeding.32,33,34,35 Pre-exposure prophylaxis should be continued until the partner living with HIV has initiated ART and achieved viral suppression (viral load < 200 copies/mL). Drug using individuals Needle sharing caries high HIV risk Pre-exposure prophylaxis has been shown to be effective in one large RCT and some demonstration studies of intravenous drug using populations of both sexes. Transgender people Anal and oral sex Transgender (TG) women have very high rates of HIV acquisition and PrEP is effective although specific evidence is limited. MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir disoproxil fumarate; RCT, randomised controlled trial; TAF, tenofovir alafenamide; FTC, emtricitabine; ART, antiretroviral therapy; HIV, human immunodeficiency virus. †, Oral sex involves using the mouth to stimulate the penis (fellatio), vagina (cunnilingus) or anus (anilingus). The chance an HIV-negative person will get HIV from oral sex with an HIV-positive partner is extremely low and lower than anal or vaginal sex. The risk of HIV transmission through oral sex is even lower if the HIV-negative partner is taking PrEP. When should pre-exposure prophylaxis not be Understanding and insight of potential PrEP user: offered? To ensure that the PrEP user understands what PrEP is and the protection it provides, and has a personal plan Pre-exposure prophylaxis should not be offered to anyone for its effective use who is suspected or confirmed to be HIV-positive. Providing PrEP to an individual who is HIV-positive or Human immunodeficiency virus-negative status of acutely seroconverting is sub-optimal treatment for user: To ensure that the PrEP user is confirmed to be HIV and could lead to antiviral drug resistance. HIV-negative (rapid HIV testing acceptable) Individuals who refuse to HIV test should be counselled Suitability and safety of PrEP for user: To assess the and PrEP should not be offered. suitability and safety of PrEP in those with renal and/or Pre-exposure prophylaxis should be delayed in anyone other potential contraindications. with an acute viral illness that could be because of HIV seroconversion. There is considerable overlap in Step 2: Test for human immunodeficiency virus status: symptoms and signs caused by viruses; therefore, any Human immunodeficiency virus testing is required at potential PrEP client presenting with fever, myalgia, initiation and at least 3 monthly whilst on pre-exposure arthralgia, rash, headache, and oral or genital ulcers prophylaxis to confirm HIV-negative status might be HIV-positive but in the window period. Other Follow HIV testing guidelines. HIV prevention options, like condoms, should be Elicit a medical history and conduct a targeted discussed, repeat testing should be arranged for 2 weeks later, with PrEP offered then if repeat test is negative. examination to exclude acute exposure (symptoms Tenofovir-based PrEP should not be offered to anyone with suspicious of acute infection may be followed with repeat pre-existing renal dysfunction (Estimated glomerular testing after 2 weeks to confirm HIV-negative status). filtration rate i [eGFR] < 50 mL/min). Clients can return in Human immunodeficiency virus testing is advised 3–6 1–3 weeks to re-test eGFR to re-assess eligibility. monthly whilst on PrEP to ensure breakthrough infection Individuals < 35 kilograms (kg) should not be given has not occurred. oral PrEP. Human immunodeficiency virus self-testing may be used as an alternative whilst on PrEP. Simplifying pre-exposure prophylaxis to improve Inconclusive HIV test results should be referred for access and optimise use confirmatory testing. Pre-exposure prophylaxis is safe, well tolerated and easy Pre-exposure prophylaxis should be stopped immediately to administer in anyone with a positive or indeterminate HIV test result. Step 1: Check client desirability of pre-exposure prophylaxis: Should an interruption in PrEP occur, then initiation The aims of initiation consultations for PrEP are: testing should be performed (as above) prior to restart. http://www.sajhivmed.org.za Open Access  Page 4 of 8 Guideline Step 3: Check general well-being: Clinical assessment: A Immediate access to antiretroviral therapy (ART) for clinical assessment for STIs should be performed at initiation, potential PrEP users who screen HIV-positive and require 6 monthly or when indicated. treatment. Appropriate STI screening is recommended and aetiologic A prescription for PrEP (or PrEP medication) should be testing and treatment should be provided when available. provided for a 3-month start. This should include nucleic acid antigen testing for Adolescents and younger users or those who have Chlamydia trachoma and Neisseria gonococcus and serology identified pill-taking difficulties may be invited to return for Treponema pallidum. after 1 month to troubleshoot adherence difficulties. Syndromic STI screening and management is otherwise Telephonic contact may help with mild side effect recommended. management and difficulties with establishing pill-taking Viral hepatitis B screening is recommended at PrEP routines. initiation and screening if status is unknown. A follow-up visit for clinical monitoring, counselling on Hepatitis B vaccination is recommended if available or if persistence at 3 months, and then every 6 months or as screening serology test is negative. required. Again, younger users may benefit from more regular contact. Step 4: Check for contraindications: Renal function: A baseline assessment of renal function should be performed Tips to support pre-exposure prophylaxis pill-taking (creatinine and eGFR) in patients who are above 40 years of Schedule medication taking time to correspond with the age, have co-morbidities or are on concomitant medication. client’s daily routine activities (e.g. brushing teeth, eating Pre-exposure prophylaxis should not be used in people breakfast and going to bed). with a baseline eGFR of < 50 mL/min. Renal function may Take pills at night if worried about side effects (e.g. in be checked annually and more frequently as dictated by an pregnant women). underlying renal problem or comorbidity. Use reminders, for example, cell phone, alarms, beepers Step 5: Plan follow-up visits: and calendars​. Use pillboxes to ensure daily use.​ Assess how pill-taking is going for PrEP user​. Review disclosure issues to identify those who can Interactions should be supportive and affirming. support the client’s intentions to take their pills or barriers Identify a motivator to support effective pill-taking​. to pill-taking because of lack of disclosure or privacy at Provide PrEP education regarding effective use and home​. effectiveness of PrEP.​ Join an online support group, for example, Facebook: Identify barriers to effective use.​ PrEP Rethinking HIV Prevention. Provide realistic strategies to address barriers. ​ Discuss use of other HIV prevention measures that are Other considerations relevant to situation​. Stopping and starting pre-exposure prophylaxis: Unlike Review need for PrEP and any change in sexual risk. taking ART, PrEP is not a lifelong intervention and individuals should be encouraged to ascertain risk and gauge their own Step 6: Package of prevention: Providers can provide PrEP need for PrEP. Different types of prevention may also be on the same day as counselling, following HIV testing. Pre-exposure prophylaxis alone provides high levels of preferred at different times, for example, a holiday away HIV prevention; however, additional benefits are likely to versus busy working period at home. accrue if it is offered as part of a package of combination prevention that includes: Individuals should be instructed how to begin and stop daily use PrEP. Counselling on effective use, starting and stopping PrEP. Agreement for follow-up HIV testing. This is different from ‘on-demand’ PrEP, which is described Human immunodeficiency virus testing and counselling in more detail below. of sex partners (including HIV self-screening) Commodities such as condoms and sexual lubricants. Sexual health screening, including STI symptom check, Tenofovir disoproxil fumarate/FTC can only prevent HIV if aetiological STI testing if available and treatment either provided at sufficient levels in the tissues at the time of HIV syndromically or as per laboratory results. exposure. The need for loading doses has been controversial Discussions on reproductive intent and provision of and largely informed by PK modelling studies. The current contraception as needed. research suggests that as many as 7 days of oral doses may be Active safer conception counselling and guidance should required in the case of vaginal mucosal exposure to ensure be offered to women and couples who wish to conceive that sufficient tissue levels have been reached. However, (see safer conception guidelines). clinical use in cis-males and trans-women suggests that high Gender affirming counselling and treatment for TG levels of protection can be achieved with dosing just before populations. exposure. http://www.sajhivmed.org.za Open Access  Page 5 of 8 Guideline If a PrEP user’s risk changes, that is, declines, or one wishes Prevenir studies26,41 that on-demand (i.e. sex or coital based to stop PrEP for any reason, it should be affirmed that PrEP is dosing of PrEP) is effective for MSM and TG women and can not a lifelong intervention and that it is fine to stop. It is be used as an alternative to daily dosing. advised to take PrEP for up to 28 days after the last potential exposure to HIV (although this is not based on clinical On-demand PrEP involves the so-called ‘2:1:1 strategy’. evidence and alternative HIV prevention advice and PrEP users are advised to take two pills of TDF-based PrEP commodities should be discussed). Clients should be invited (i.e. a double dose) 2–24 h before sex. If sex occurs, they to return to discuss PrEP at any point in future. should follow up with one pill per day for the following 2 days after sex. Risk disinhibition: Pre-exposure prophylaxis is highly efficacious and therefore it is unlikely even with more This strategy allows minimisation of unnecessary PrEP condomless sex that HIV infection will occur. Most studies doses when HIV exposure is unlikely (no sex) and therefore have shown that increased access to care has resulted in less might decrease the risk of cumulative side effects. The risky sex but in practice PrEP may result in more STIs and strategy might suit individuals who do not want to take unintended pregnancies. For effective PrEP services, STI pills daily, allowing prevention doses to be focused around screening, appropriate treatment and prevention as well as the time of HIV exposure risk. Should someone initiate on- contraception should be offered as part of an integrated demand PrEP, they should be counselled on the strategy sexual and reproductive health service at each PrEP clinical and similar initiation precautions and investigations consultation. should be done. Human immunodeficiency virus status should be confirmed as negative, they should be considered for renal function testing and should attend their health Sexually transmitted infections and pre-exposure provider regularly for STI screening and repeat HIV testing. prophylaxis: Where feasible, a sexual history and a targeted New prescriptions should be administered as often as examination is recommended to guide further screening and required. management, taking into account that STIs occur at all anatomic sites including oral, vaginal, penile and anal sites. Newer pre-exposure prophylaxis options The frequency of screening should be individualised and guided by the sexual history. We recommend that STI A recently added ARV shown to be effective for oral PrEP is screening should occur at least annually and more frequently a tenofovir (TFV) pro-drug called TAF that is approved in (6 monthly) in key populations such as MSM,36,37 pregnant combination with other ARV agents for the treatment of women38,39,40 and sex workers. High rates of asymptomatic HIV-1 infection in adults and paediatric patients. Tenofovir Chlamydia trachomatis (CT) are occurring amongst young alafenamide has PK properties that distinguish it from TDF, women and MSM in the region. For this reason, where resulting in clinically meaningful benefits that improve possible, nucleic acid amplification test (NAAT) testing for safety and increase the efficacy of TAF over TDF in PrEP. gonorrhoea and CT are highly recommended, but these tests The lower levels of circulating TFV have consistently been are expensive and not always available. Syndromic STI associated with improved measures of renal and bone safety screening and management should be offered as an laboratory markers. Emtricitabine + TAF fixed dose combination pill (F/TAF) was shown in the recently alternative. published Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV Post-exposure prophylaxis to pre-exposure prophylaxis: pre-exposure prophylaxis (DISCOVER) trial to be non- Individuals who frequently require post-exposure inferior to F/TDF and has thus been licensed by the FDA for prophylaxis (PEP) for HIV exposure may benefit from PrEP. oral PrEP use in men and TG women.42 An equivalent trial On completion of 28 days of triple ARV PEP therapy, oral is being designed for cisgender women in which TAF use in PrEP may be continued with ongoing maintenance as before. pregnancy will also be explored. Individuals who have a break between PEP and PrEP initiation should initiate as recommended above. Long-acting cabotegravir which is a depot injectable integrase PrEP agent has just been shown to be non-inferior to oral TDF/FTC in a randomised clinical trial of MSM and Broaden pre-exposure prophylaxis modalities to TG women (HPTN 083).43 The companion study of include on-demand pre-exposure prophylaxis in cabotegravir long acting in African women is still underway men who have sex with men and transgender (HPTN 084, the Life Study, NCT03164564).i women i.With regard to long-acting single-agent injectable antiretroviral cabotegravir in the On demand pre-exposure prophylaxis pre-exposure prevention (PrEP) of HIV infection/transmission to HIV-uninfected women (Study HPTN 084) and men (Study HPTN 083), both demonstrate superior There is now robust evidence from the Intervention Préventive efficacy versus standard oral PrEP. In the HPTN 084 Study, cabotegravir given every two months was 89% more effective than daily pills at preventing HIV acquisition. de l’Exposition aux Risques avec et pour les Gays (IPERGAY), London, 9 November 2020. https://clinicaltrials.gov/ct2/show/NCT03164564. (HTPN and Intervention Préventive de l’Exposition aux Risques avec 084); https://clinicaltrials.gov/ct2/show/NCT02720094. (HTPN 083). Editor’s comment: Note that this data will still require approval from international and local et pour les Gays (IPERGAY) Open Label Extension (OLE) and agencies. Cabotegravir is not currently registered for use in South Africa. http://www.sajhivmed.org.za Open Access  Page 6 of 8 Guideline Finally, the topical dapivirine vaginal ring has just been peri-menopausal women and those with a history of recommended by the European Medical Agency as a PrEP fragility fractures), the use of TAF or episodic TDF (to reduce intervention for women unable to safely utilise oral PrEP. exposure) could be considered. This preventive tool was shown to reduce HIV acquisition by about 30% in women at risk of HIV acquisition in two Hepatitis B: Tenofovir disoproxil fumarate is also an RCTS conducted in Africa.44 antiviral treatment for hepatitis B. For this reason, screening for hepatitis B surface antigen is recommended prior to Updates to adverse events and drug–drug starting PrEP, but should not prevent PrEP start. Hepatitis interactions B infection is also not a contraindication for PrEP use in Adverse events individuals who would benefit. Caution when stopping Tenofovir disoproxil fumarate and TAF are safe and well- PrEP may be required in those who are hepatitis B surface tolerated drugs. Side effects do not occur in 90% or more antigen positive. Rebound of hepatitis B virus resulting clients who start PrEP. Initial minor side effects including in liver injury has been described in the setting of ART and headache and gastrointestinal upset (i.e. diarrhoea, nausea not PrEP but remains a theoretical concern. Hepatitis B and loss of weight) may be experienced in up to 10% of vaccination is recommended for those who are hepatitis people taking PrEP, but are self-limiting, with resolution surface antigen negative. within 2–3 weeks.3 These can be managed symptomatically. Tolerance improves over time. Drug resistance: Drug resistance mostly occurs when PrEP is initiated at a time when the client is acutely HIV infected Renal toxicity: A creatinine clearance (CrCl) test is and is seroconverting. During these times, viral replication recommended at the time of PrEP commencement to occurs rapidly in the blood. Pre-exposure prophylaxis drug exclude asymptomatic renal disease but is not essential in concentrations are still suboptimal. Clients who seroconvert well individuals under the age of 40 years and should not should stop PrEP use immediately and initiate ART as soon delay PrEP start. Tenofovir may cause a 5 mL/min – 6 mL/ as possible. Monitoring of ART should follow adult min reduction in CrCl in the first few months of use and if treatment guidelines. this prompts a PrEP pause, PrEP may be re-introduced in most cases without further problems. Drug–drug interactions Transgender women on feminising hormonal treatment In pregnant women, individuals > 40 years of age, those with were thought to be in danger of drug–drug interactions a chronic disease and those using concomitant medications, with reduced efficacy of PrEP; however, a recent study creatinine should be drawn the same day as PrEP start has shown this is not the case.45 (results can be communicated later) and repeated at months 6 and 12. More frequent monitoring of renal function may be Tenofovir disoproxil fumarate is largely eliminated by the required for people with chronic diseases such as kidneys. There are few drug interactions of note, but TDF hypertension and diabetes, as per the plan for that should be used with caution with medications that cause comorbidity. Tenofovir disoproxil fumarate should not be renal toxicity (see Table 3). commenced if the CrCl is < 50 mL/min, and should be stopped if the CrCl declines below 50 mL/min. The client Conclusion can re-test within 1 month to establish if their CrCl changes We expect guidelines to be updated on a regular basis in and can start PrEP then. Where renal toxicity is an issue, TAF/FTC may be considered as an alternative agent because line with ongoing research on vaginal rings, new drugs of its renal sparing properties (see Table 2). (including TAF), new regimens and injectable PrEP. South Africa is involved in several clinical trials. Bone mineral density: There is evidence for bone density Longer term and, on-demand modalities are compelling loss with long-term use of TDF. For those with risk factors alternatives for individuals who either do not want to for reduced bone mineral density (BMD) (e.g. adolescents, take a daily pill and, or want to take PrEP intermittently. people using recreational drugs such as amphetamines, Emerging modalities such as vaginal films, microneedles people > 60 years of age, with known low BMD, post- and and subdermal implants have numerous advantages but TABLE 2: Creatinine monitoring with tenofovir disoproxil fumarate pre-exposure prophylaxis. Variable At PrEP start At PrEP follow-up Well individual, ≤ 40 years Recommended, not essential Not required > 40 years Recommended 6 and 12 months Pregnant Recommended 6 and 12 months; not required after pregnancy if ≤ 40 years Comorbidities Recommended 6 and 12 months Concomitant chronic medication Recommended and essential or contra-indicated if nephrotoxic 6 and 12 months/contraindicated concomitant medication PrEP, pre-exposure prophylaxis. http://www.sajhivmed.org.za Open Access  Page 7 of 8 Guideline TABLE 3: Drug interactions with tenofovir disoproxil fumarate. Drug name Interaction Response Aminoglycosides (e.g. amikacin and gentamicin used in drug-resistant TB) Possible additive nephrotoxicity Avoid concomitant TDF TDF, tenofovir disoproxil fumarate; TB, tuberculosis. PrEP offering: The time at which someone may be introduced to and invited to consider PrEP based on the anticipation/expectation of potential HIV exposure and lifestyle. PrEP initiation: The point at which someone takes a bottle of pills home with the intention of using them effectively. Offering of PrEP and initiation can occur during a single consultation if the client is knowledgeable and motivated to take PrEP. Effective use: When drug levels in blood are high, PrEP is highly protective. For most populations, PrEP should be taken daily to prevent HIV. In heterosexual men and women, daily dosing is recommended (see below). In men who have sex with men (MSM), on-demand PrEP can be used according to 2:1:1 strategy, whereby two pills of TDF-based PrEP (i.e. a double dose) are taken 2–24 h before sex. If sex occurs, this should be followed up with one pill per day for 2 days after sex. The term ‘effective use’ is a preferred terminology to ‘adherence’ to PrEP. Persistence: Persistence refers to the consistency of taking PrEP over time. Persistence on PrEP is important for maintaining and increasing current reductions in new HIV infections. Not all patients who initiate PrEP stay on it for long term, nor should they if their risk profile changes. ‘Persistence’ is the preferred terminology to ‘retention’ on PrEP. Cycling on and off/seasons of use/episodic use: PrEP use and interruption, based on HIV risk behaviours including sex partners’ HIV status, number of sex partners, sexual activity and condom use. Client: Person who uses PrEP or is interested in using PrEP. The term ‘client’ is preferred rather than ‘patient’. Potential exposure: Any potential sexual or other exposure to HIV. The term ‘potential exposure’ is preferred to ‘risk of HIV’. On-demand PrEP: PrEP that is used at the time of a sexual event in which a potential HIV exposure could occur. This may overlap with post-exposure prophylaxis. Preferred PrEP term NOT preferred Offering Screening Initiation Enrolment Effective use Adherence Persistence Retention Cycling off Loss to follow-up Client Patient Potential for exposure Risk PrEP, pre-exposure prophylaxis; TDF, tenofovir disoproxil fumarate; ARV, antiretroviral; ART, antiretroviral therapy; HIV, human immunodeficiency virus. FIGURE 1: Pre-exposure prophylaxis introduces a new lexicon. are still in early stages of development. Oral PrEP is a Data availability statement discreet, user-dependent, safe and effective prevention Data sharing is not applicable to this article as no new data modality which is now part of the South African were created or analysed in this study. standard of HIV prevention. Adolescents and adults who deem themselves to be at risk of acquiring HIV can be offered this modality to enable safer sexual activity Disclaimer and worry-free intimate relationships. 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