When initiating therapy for HIV-1 infection in adults, clinicians should keep a couple of things in mind because the paradigm for therapy has changed. The main shift is that we are no longer waiting for the results of viral genotype testing prior to initiating treatment. Treatment is being initiated either on the day of diagnosis of HIV infection or after prompt referral to the infectious disease specialty clinic. This is in contrast to several years ago, when patients would be seen in an HIV clinic and then several days or weeks would pass while viral genotype testing was being performed before therapy was selected. There is now little or no treatment delay as it is considered best practice to start patients on a therapy to which the virus would be most sensitive.
When looking at the current HIV-1 treatment guidelines, it is clear that most regimens are integrase-based along with a combination of tenofovir alafenamide/emtricitabine (TAF/FTC).1 A typical patient with newly diagnosed HIV-1 infection and who has not received any treatment can be started on these 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), regardless of their CD4 count and viral load. In patients who have received treatment, we have been switching from regimens containing tenofovir disoproxil fumarate (TDF) to regimens with TAF, due to concerns about renal dysfunction and loss in bone mineral density.
Another big advantage of TAF/FTC-based combination therapy is that it can be used in patients with an estimated creatinine clearance as low as 30 mL/min, which represents a marked improvement over TDF-based regimens.
Treatment regimens containing TAF/FTC are generally very well tolerated. Short-term adverse events include nausea, vomiting, and diarrhea. These gastrointestinal effects are reported in up to 16% of patients in some clinical trials,2 but in my practice I have hardly ever had a patient complain of persistent diarrhea or nausea. The long-term potential side effects include renal insufficiency and metabolic sequelae, including increased serum cholesterol and triglyceride levels. In our clinic, we have not seen any significant changes in renal function or bone mineral density with regimens containing TAF-FTC. We had noticed a slight increase in serum cholesterol solely due to the switch from TDF to TAF, but it did not require initiation of lipid-lowering therapy.
Clinical trials evaluating the efficacy of a protease inhibitor or an integrase inhibitor in combination with TAF/FTC for HIV-1 infection have shown that TAF/FTC-based regimens effectively suppress HIV-1 viral load.3 Anywhere from 90% to 92% of enrolled clinical trial participants have gone on to have an undetectable HIV-1 RNA viral load,4 showing that the response rates to these medications are excellent. Further research evaluating the efficacy of TAF/FTC for HIV pre-exposure prophylaxis revealed that TAF/FTC combination therapy was noninferior to TDF/FTC.5 TAF/FTC is now approved by the US Food and Drug Administration for HIV prevention in men who are at risk for infection yet are HIV negative and transgender women who have sex with men (Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide [F/TAF] Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection [DISCOVER]; ClinicalTrials.gov Identifier: NCT02842086).
Practically speaking, clinicians should always check the hepatitis B virus status of a patient before initiating treatment with TAF/FTC. This is important because if NRTI treatment is stopped, hepatitis B infections can flare quickly. Secondly, clinicians should be aware of communicating the importance of adherence to HIV therapy to their patients. Our clinic will sometimes set up daily pill boxes for patients if we think there is any concern related to medication adherence. The good thing about newer combination therapy is that the pill number has been reduced, sometimes to a single pill a day, with no specific time they need to be taken. So we tell patients to pick a convenient time when they know they will be able to take their medications every day. Our clinic also advises patients to come back 4 weeks following treatment initiation so we can review how the therapy is going.
Clinicians should be aware of guidelines for HIV therapy in special patient populations, including patients who are pregnant or breastfeeding. In general, breastfeeding is still discouraged in patients receiving treatment for HIV-1 infection in the United States, since we still do not have enough data to outline the risk for transmission to the infant during breastfeeding. In the past, if a woman became pregnant while on TAF/FTC-based regimen, we would switch her to a TDF-containing regimen. However, now we continue the same regimen and monitor the mother’s HIV viral load to ensure that the maternal viral load remains undetectable to prevent vertical transmission of HIV to the infant.
Clinicians should also be aware of the rare risk for immune reconstitution syndrome, which is a period when underlying opportunistic infections may worsen. One of our patients was diagnosed with HIV and started on antiretroviral therapy, but approximately 3 months later she presented with worsening mental status changes. Her CD4 cell count at the time was around 300. Magnetic resonance imaging was conducted and showed that she had progressive multifocal leukoencephalopathy, which was basically a result of immune reconstitution syndrome. At that point, we told the patient that we just have to continue to monitor her, treat the underlying opportunistic infection, and continue the antiretroviral therapy.
Disclosures: Dr Brar has served on speakers bureaus and received research funding from several pharmaceutical companies, including ViiV Healthcare; Janssen Global Services, LLC; and Gilead Sciences, Inc.
1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed January 15, 2020.
2. Emtricitabine/tenofovir alafenamide side effects. Drugs.com website. https://www.drugs.com/sfx/emtricitabine-tenofovir-alafenamide-side-effects.html. Updated February 8, 2019. Accessed January 15, 2020.
3. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. AIDSinfo website. https://aidsinfo.nih.gov/contentfiles/lvguidelines/glchunk/glchunk_11.pdf. Updated December 18, 2019. Accessed January 15, 2020.
4. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385(9987):2606-2615.
5. Hare CB, Coll J, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presentation at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle, WA. Abstract 104LB.