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Honorary Associate Professor
Institute for Global Health
University College London
Consultant in HIV Medicine
Ian Charleson Day Centre
Royal Free Hospital
London, United Kingdom
Tristan J. Barber, MA, MD, FRCP, has disclosed that he has received funds for research support from Roche; consulting fees from Gilead Sciences, MSD, Theratechnologies, and ViiV; fees for non-CME/CE services from Gilead Sciences, MSD, and ViiV; and other financial or material support from Gilead Sciences and ViiV.
London was the first city to meet and exceed the UNAIDS 90-90-90 targets and the first to exceed 95-95-95, meaning more than 95% of patients aware of their HIV status, 95% receiving antiretroviral therapy (ART), and 95% virologically suppressed. Nonetheless, we continue to see a slow but steady stream of people diagnosed with HIV late, and often they are being admitted to our wards with AIDS-defining conditions. In 2021, this feels like a travesty. These often are people who have not perceived that testing and prevention messages are for them and people who have not been offered an HIV test in the medical settings where they have been seen, including emergency departments, primary care, and outpatient clinics.
Although suspected primary HIV infection demands that we consider early ART initiation (“test and treat”), in late diagnosis, it feels prudent to gather and offer information before rushing in with medication. Very often, late-presenting patients may not be HIV literate, and education and support are imperative before offering lifelong daily medication. The aim is not only to treat viremia, but also to ensure good understanding of the need for adherence and attending regular follow-up. In addition, it is important to ensure that there is no risk of opportunistic infection (or the potential for an unmasking of one) following ART and subsequent immune reconstitution.
Once baseline blood results are obtained, including hepatitis markers and HIV resistance testing, we have a range of medicines that suit themselves to this stage of HIV infection. We also must consider trial data and, when necessary, ensure that we have evidence that our ART choices will be effective in patients with low CD4+ cell counts or high HIV-1 RNA.
In line with global ART guidelines, second-generation integrase strand transfer inhibitors (INSTIs) are the drug of choice in late-presenting patients, as with most patients. In practice, we commonly use dolutegravir (DTG) with tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) (depending on the scenario) and either lamivudine (3TC) or emtricitabine (FTC). In those for whom a single tablet is important, bictegravir/FTC/TAF may be suitable and a good choice, if available.
Although the GEMINI-1 and-2 studies support the use of DTG/3TC in initial therapy, in clinical practice prescribers often still favor an “induction” approach with 3-drug ART. However, in those without HIV resistance mutations or with hepatitis B coinfection, a simplification to DTG/3TC once undetectable is a pragmatic approach. In those for whom an INSTI is not considered appropriate, doravirine may be selected, with the same choices regarding backbone. For late-presenting patients with less predictable adherence and without a risk of serious drug–drug interactions, we may use a boosted protease inhibitor, often darunavir (DRV) boosted with either cobicistat (COBI) or ritonavir and, again, TAF or TDF with a 3TC or FTC backbone. If available, the coformulated single tablet of DRV/COBI/TAF/FTC is increasingly popular.
We must act now for wider HIV testing, and we must ensure that all those with HIV have access to ART and are being supported in care for both their physical and mental health. Without access and support, the number of people with transmissible HIV will continue to fuel onward transmissions, and the goal of achieving zero HIV transmissions by 2030—so near with concerted effort—may remain just out of reach.
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