HIV update: Which single-tablet regimens, and when

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Applied Evidence

HIV update: Which single-tablet regimens, and when

J Fam Pract. 2016 November;65(11):762-764,766-768

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References

1. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Concorde Coordinating Committee. Lancet. 1994;343:871-881.

2. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at: http://www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0. Accessed July 17, 2016.

3. The INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795-807.

4. The TEMPRANO ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373:808-822.

5. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375:830-839.

6. Molina JM, Clotet B, van Lunzen J,et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomized, open-label, phase 3b study. Lancet HIV. 2015;2:e127-136.

7. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369:1807-1818.

8. Van Lunzen J, Maggiolo F, Arribas JR, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naïve adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomized, phase 2b trial. Lancet Infect Dis. 2012;12:111-118.

9. Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS. 2013; 27:1771-1778.

10. Mallal S, Phillips E, Carosi G. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358:568-579.

11. AIDSinfo Drug Database. Dolutegravir. Available at: https://aidsinfo.nih.gov/drugs/509/dolutegravir/0/professional. Accessed July 17, 2016.

12. AIDSinfo Drug Database. Emtricitabine. Available at: https://aidsinfo.nih.gov/drugs/208/emtricitabine/0/patient. Accessed July 17, 2016.

13. AIDSinfo Drug Database. Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate. Available at: https://aidsinfo.nih.gov/drugs/553/genvoya/0/professional. Accessed July 17, 2016.

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16. Wohl DA, Cohen C, Gallant JE, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e118-120.

17. Clumeck N, Molina JM, Henry K, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e121-124.

18. AIDSinfo Drug Database. Cobicistat. Available at: https://aidsinfo.nih.gov/drugs/537/evotaz/0/patient/. Accessed July 17, 2016.

19. Rockstroh JK, DeJesus E, Lennox JL, et al. Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naïve HIV-1 infected patients: final 5-year results from STARTMRK. J Acquir Immune Defic Syndr. 2013;63:77-85.

20. Cahn P, Kaplan R, Sax P, et al. Raltegravir (RAL) 1200 mg once daily (QD) is non-inferior to RAL 400 mg twice daily (BID), in combination with tenofovir/emtricitabine, in treatment-naive HIV-1-infected subjects: week 48 results. Abstract FRAB0103LB presented at: 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa.

21. Hicks C, Gulick RM. Raltegravir: the first HIV type 1 integrase inhibitor. Clin Infect Dis. 2009;48:931-939.

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24. Marcus JL, Chao C, Leyden W, et al. Narrowing the gap in life expectancy for HIV+ compared with HIV- individuals. Conference on Retroviruses and Opportunistic Infections. February 22-25, 2016, Boston. Abstract 54.

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Initiation of antiretroviral therapy

The US Department of Health and Human Services (DHHS) guidelines now recommend that all people infected with HIV, regardless of CD4 cell count, begin ART.²The evidence for this recommendation comes largely from the START³ and TEMPRANO⁴ trials, which found that early initiation of ART significantly reduces morbidity and mortality associated with HIV. In addition, the HPTN 052 study concluded that early ART is associated with a 93% lower risk of viral transmission in serodiscordant heterosexual couples.⁵ The DHHS guidelines do note that when initiating ART, it is important to appropriately educate patients on the benefits of treatment and address strategies to optimize adherence.² (For more on factors to consider when selecting an initial HIV regimen, see TABLE 1.²) On a case-by-case basis, ART may be deferred because of clinical and/or psychosocial factors, but it should never be withheld unless the risks clearly outweigh the benefits. Ideally, ART should be initiated as soon as possible after the initial diagnosis of HIV.

The DHHS guidelines divide treatment options into 3 categories:²

Recommended regimens are backed by randomized controlled trials that show optimal and durable virologic efficacy, they have favorable tolerability and toxicity profiles, and they are easy to use.
Alternative regimens have less or lower quality supporting data than recommended regimens. Although they are effective and may be optimal for certain individual patients, they have potential disadvantages and/or limitations in certain populations.
Other regimens have limited supporting data, reduced virologic activity, a higher pill burden, more drug interactions, and greater toxicity.

Currently recommended first-line therapies

An antiretroviral regimen for a treatment-naive patient should consist of 2 NRTIs in combination with a third active antiretroviral drug from one of 3 drug classes. These include: an INSTI, a boosted PI, or, in some situations, an NNRTI. The DHHS guidelines panel currently recommends 6 different ART combinations as first-line treatment in treatment-naive patients (TABLE 2).²