Recent updates on HIV prevention and treatment in Singapore

Human immunodeficiency virus (HIV) infection remains a public health priority in Singapore. The National Centre for Infectious Diseases (NCID) established the National HIV Programme (NHIVP) to coordinate the country-wide HIV response in collaboration with clinicians, healthcare professionals, public health practitioners, and other stakeholders. The NHIVP develops and updates evidence-based guidelines and best practices on HIV prevention, testing, and treatment. This article summarizes the best practices and key updates on prescribing of HIV pre-exposure prophylaxis (PrEP), and use of antiretroviral therapy (ART) in Singapore.

Singapore’s progress towards ending the AIDS epidemic
In 2016, the United Nations General Assembly’s Political Declaration on Ending AIDS committed countries to the ‘90–90–90’ targets — whereby 90 percent of all people living with HIV (PLHIV) will know their status, 90 percent of those diagnosed will receive sustained ART, and 90 percent of those on ART will have viral load suppression by 2020. The global target was not met, with corresponding estimates of 81 percent, 66 percent, and 59 percent, respectively. [https://www.unaids.org/en/resources/909090; Accessed 15 Feb 2022]

Of the estimated 8,000 PLHIV in Singapore in 2020, 84 percent knew their status, 75 percent were on ART, and 73 percent had undetectable viral loads. Among PLHIV who knew of their status, 89 percent were on treatment. More than 95 percent of those on ART achieved viral suppression. [https://aphub.unaids.org/; Accessed 15 Feb 2022]

Importantly, an overwhelming body of clinical evidence has firmly established the concept of Undetectable = Untransmittable (U=U) for HIV. U=U means that PLHIV who achieve and maintain an undetectable viral load by taking ART daily as prescribed cannot sexually transmit the virus to others. [https://www.niaid.nih.gov/diseases-conditions/treatment-prevention; Accessed 15 Feb 2022] Thus, maintaining an undetectable viral load is of paramount importance not only to improve outcomes for PLHIV, but also for HIV prevention.

Pre-exposure prophylaxis (PrEP) recommendations
PrEP is an evidence-based, highly effective biomedical addition to the suite of behavioural measures to prevent HIV transmission and infection. PrEP involves the daily consumption of HIV preventive medication by HIV-negative patients who are assessed to be at high risk of acquiring HIV infection. It is highly effective when taken as prescribed. Local recommendations are important to guide the use of this powerful tool in Singapore. [https://www.ncid.sg/About-NCID/OurDepartments/Pages/National-HIV-Programme.aspx; Accessed 15 Feb 2022]

According to the NHIVP guidance, PrEP may be suitable for someone who is HIV-negative and if the person:
•            Has a sexual partner with HIV who is not on suppressive ART
•            Is at risk of getting HIV through vaginal/anal sex with multiple partners without the consistent use of condoms in the past 6 months
•            Had any sexually transmitted infections in the past 6 months
•            Has received HIV post-exposure prophylaxis in the past 6 months
•            Reports concerns about the consistent use of condoms in the future
•            Engages in sexual activities under the influence of alcohol or other drugs

PrEP is contraindicated in patients with known HIV infection, clinical syndrome suggestive of acute HIV infection/HIV seroconversion, known impairment of renal function (estimated creatinine clearance CrCl <60 mL/min for emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) and <30 mL/min for FTC/tenofovir alafenamide (TAF); allergy or other known contraindications to any of the drugs in the PrEP regimen.

Summary of PrEP regimens available
Currently, PrEP regimens include a combination of two antiviral medications: FTC and tenofovir (TDF or TAF) (Table 1).

Before starting PrEP, providers need to document important aspects of patients’ history, which include thorough sexual history, HIV and STD screens in the past year, and history of bone or renal disease. Patients should be counselled on the importance of 3-monthly HIV/STD screens, taking of FTC/TDF or FTC/TAF for PrEP as directed, and risk reduction advice, including for other STDs.

Testing is required to ensure the patient is HIV negative, and baseline evaluations and screening (renal function, hepatitis B, hepatitis C, STDs, pregnancy) should be conducted. Prescriptions for PrEP should not exceed 3 months. After PrEP is started, 3-6 monthly reviews are required for HIV/STD screens. The need for continued PrEP should be determined every 12 months, based on assessment of the patient’s risk for HIV infection. Those who test positive for HIV should be referred to an HIV care centre urgently and can be started on an HIV treatment without interruption. [https://www.ncid.sg/About-NCID/OurDepartments/Pages/National-HIV-Programme.aspx; Accessed 15 Feb 2022]

NHIVP recommendations for ART use
The advent of combination ART has reduced the mortality attributable to HIV infection by 80 percent. [PLoS One 2014;9:e87872] ART also reduces the risk of HIV transmission. The NHIVP recommendations on the use of ART adapt international guidelines to the local context, to reflect locally transmitted drug resistance trends, health economics, and drug availability.

Treatment regimens for ART-naïve patients
The 2021 updates reflect changes to first-line regimens, with a greater emphasis on integrase strand transfer inhibitors (INSTI) in view of the advantages they provide. Both dolutegravir (DTG)- and bictegravir (BIC)-based regimens are listed as preferred first-line regimens (Table 2). If INSTI-based regimens cannot be used, non-nucleoside reverse transcriptase inhibitor (NNRTI)- and darunavir/ritonavir (DRV/r)-based regimens can be considered as alternative first-line regimens.

2021 NHIVP update: Biktarvy listed as a preferred first-line option
BIC is the most recent addition to the INSTI class and has been compared with DTG for the initial treatment of HIV as a part of a complete three-drug regimen. In Singapore, BIC is only available as a co-formulation with FTC and TAF. The BIC/FTC/TAF combination tablet (Biktarvy®) was approved by the Singapore Health Sciences Authority in 2019 as a once-daily single tablet regimen for the first-line treatment of HIV-1 infection in adults, or to replace the current antiretroviral regimen in those who are virologically-suppressed on a stable antiretroviral regimen for at least 3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.

Multiple, double-blind, randomized controlled trials have demonstrated the noninferiority of BIC/FTC/TAF to standard-of-care DTG-based regimens in terms of efficacy, including DTG/3TC/ABC and DTG/FTC/TAF. [Lancet HIV 2020;7:e389-e400] While the rates of adverse events were similar among regimens, BIC-based regimens showed better gastrointestinal tolerability than DTG-based regimens. [Lancet 2017;390:2063-72; Lancet 2017;390:2073-82]

Another advantage of using the BIC/FTC/TAF regimen is that HLA B*57:01 testing is not required, making it suitable for rapid or same-day initiation of therapy. In addition, TAF can be used for the treatment of hepatitis B virus (HBV) infection, making it a convenient option for patients co-infected with HIV-1 infection and hepatitis B. [Lancet HIV 2020;7:e389-e400; Pharmacotherapy 2018;38:1051-1057]

Abacavir-based regimen
Another preferred first-line option is DTG/3TC/ABC. NHIVP suggests HLA-B*57:01 screening prior to the use of ABC for non-Chinese patients only, including Malay and Indian patients with late-stage HIV, for reasons of cost-effectiveness. In line with international guidelines, NHIVP recommends that ABC be avoided in patients with high cardiovascular risk, or with a documented history of ischaemic heart disease. The combination of ABC/3TC should also be avoided in individuals with HIV-HBV co-infection [https://www.ncid.sg/About-NCID/OurDepartments/Pages/National-HIV-Programme.aspx Accessed 15 Feb 2022]

In terms of NRTI-sparing regimens, DTG + 3TC is recommended. RAL-based regimens are no longer recommended as first-line regimens, as RAL has a lower genetic barrier to resistance compared with DTG and BIC. [Lancet 2013;381:735-743; Antimicrob Agents Chemother 2016;60:7086-7097]

Switching regimens
In patients who have achieved virologic suppression for >6 months, ART regimens may be changed or switched for various reasons, such as costs, reduction of side effects, or simplification of drug regimen (Table 3).

Take-home messages
·       The PrEP guidance will help in evaluating patients seeking PrEP, and when commencing and monitoring patients on PrEP. Regimens include co-formulated FTC/TDF (suitable for all PrEP patients) or FTC/TAF (in selected populations).
·       The ART recommendations offer guidance on ART use in PLHIV in Singapore. BIC/FTC/TAF (Biktarvy) is the newest addition to the list of preferred first-line therapies for HIV-1 infection in adults.