Terminology

Treatment as prevention (TasP) refers to the use of antiretroviral drugs to decrease the risk of HIV transmission. When taken consistently, antiretroviral drugs can reduce the HIV viral load in an HIV-infected individual’s blood, semen, vaginal fluid and rectal fluid to a level at which blood tests cannot detect the virus ^[17]. Such viral load is considered ‘undetectable’ and equivalent to viral suppression.

The concept of TasP and evidence of its public health and individual benefits 

The relationship between HIV viral load and HIV transmission probability was first reported in 2000 by Quinn and colleagues based on their observations from the Rakai cohort in Uganda. ^[18] That study concluded that the risk of HIV transmission was negligible with serum HIV-1 RNA levels of less than 1500 copies/mL. The critical importance of HIV viral load in sexual HIV transmission was observed by other studies as well. ^[19] Several subsequent studies enabled further investigation of this by reporting methods for measuring the concentration of HIV in semen using quantitative culture ^[20], the development of a PCR technique for more accurate measurement of viral load ^[21] and the reduction in HIV viral load in both semen ^{[22, 23]} and female genital secretions during ART. ^[24]

The concept of TasP is based on the logic that ART that suppresses HIV replication should also reduce HIV transmission. In 2000, the National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH)-sponsored HIV Prevention Trials Network (HPTN) initiated research to evaluate this concept. In 2011, the HPTN 052 trial reported that, among HIV-serodiscordant couples, ART given to the HIV-positive partner with a CD4+ T cell count <550 cells/mL decreased HIV transmission to HIV-negative partners by 96% when compared with those who started ART at CD4+ T cell counts <350 cells/mL. [25]

In 2014, the PARTNER study, in which more than 1,000 heterosexual and homosexual couples were enrolled across 14 European countries and reported 58,000 episodes of sex without a condom, observed zero transmissions where plasma HIV RNA inf the HIV-positive partner was undetectable. ^[26] The Opposites Attract observational cohort study, conducted in Australia, Brazil and Thailand found no phylogenetically linked HIV transmissions in 343 MSM couples when the HIV-positive partner had undetectable plasma HIV RNA. ^[27]

Results of these three studies confirmed the undisputed effectiveness of early ART initiation as a public health HIV prevention intervention, but its value for implementation in clinical practice was sealed by the results from the Strategic Timing of AntiRetroviral Treatment (START) trial conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). ^[28] At the time, the key unanswered question for TasP was whether initiation of ART early in the course of HIV infection, when risk of AIDS is low to negligible, would provide HIV-positive people with clinical benefits that outweighed the risks. For TasP to be beneficial for HIV-positive people, early ART would have to reduce their risk of developing serious non-AIDS events as well as AIDS.

Two randomised trials addressing the question of when to start ART were completed prior to START: the Haiti trial ^[29] and HPTN 052 ^[25]. Both trials investigated whether HIV infection could be left untreated as long as the CD4+ T cell cell count remained > 200/μL. Consequently, in 2007, a global consensus was reached to commence ART at CD4+ T cell counts of < 350/μL. The specific question for the START study, when it started in 2009, was whether initiation of ART at CD4+ T cell counts of >500/μL (immediate ART) was superior to deferral of ART until the CD4+ T cell count fell to 350/μL. In addition, a broader question was whether ART could be implemented as a public health strategy (that is TasP). ^[30] The results of this study confirmed that immediate initiation of ART was superior to deferral of ART with regard to both AIDS-related and serious non-AIDS-related events, and no increased rate of adverse effects associated with this strategy was observed. There was no evidence that the beneficial effect of immediate ART differed by age, sex, race, region of the world, CD4+ T cell count, HIV viral load, or risk factors for serious non-AIDS events. ^[28] Overall, the results of this trial aligned the ART benefits to the HIV-positive individual with benefits to public health.

TasP implementation

Based on this high-quality evidence, ART is now recommended for all HIV-infected individuals upon diagnosis and irrespective of CD4+ T cell count, for both individual health and public health benefits. If used consistently as TasP, ART can eliminate mother-to-child ^[31], heterosexual ^[13] and male homosexual ^{[32, 33]} transmission of HIV infection. And, despite the lack of data for persons who inject drugs, a similar benefit can be assumed regarding prevention of HIV transmission via injecting drug use.

Undetectable is untransmittable

In recent years, support for TasP has been growing. It culminated in a consensus statement issued on 21^st July 2016 that Undetectable is equal Untransmittable. ^[34] Undetectable = Untransmittable (or U=U) is the health promotion campaign to promote understanding of the updated clinical findings that demonstrate if someone is on ART and has a sustained undetectable HIV viral load, there is effectively no risk of sexually transmitting the virus to an HIV-negative partner. ^[35] Internationally and in Australia, there is a widespread support for U=U. By 5^th May 2019, the U=U consensus statement had been endorsed by 910 organizations from nearly 100 countries worldwide. ^[36]

In July 2018, ASHM developed the evidence-based Guide for Clinicians and other Healthcare Providers to facilitate the discussion of Undetectable = Untransmittable ^[35].

Clinicians are likely to be the first resort for a person with newly-diagnosed HIV infection looking for information about HIV. Effectively, the U=U guide helps clinicians to promote knowledge about HIV transmission, facilitate discussions about HIV testing and viral load agreements, and to break down some of the stigma surrounding HIV, which remains a key reason for delaying testing or treatment. The guide addresses a number of important issues related to ART which are listed in Table 2.

Table 2. Issues to consider and discuss with patients on ART

• Evidence about U=U
• Implications of undetectable HIV viral load
• Patients who do not have a sustained undetectable HIV viral load
• PEP and PrEP for partners of HIV-positive persons;
• Disclosure in the context of U=U;
• Combination prevention for HIV and STI;
• Psychosocial support;
• Legal advice for individuals and legal obligations for clinicians
• References to additional resources for patients.