Acquired Immune Deficiency Syndrome: Antiretroviral Therapy

Key points

• Current guidelines indicate that antiretroviral therapy should be started early in all adult and adolescent patients, regardless of CD4 count, which decreases HIV-related morbidity, mortality and transmission.
• Treatment should always be a combination: usually two NRTIs (abacavir/lamivudine or tenofovir/emtricitabine) plus a third drug from one of these classes: integrase inhibitor, NNRTI, or protease inhibitor with an enhancer (cobicistat or ritonavir).
• Initial screening uses an antigen/antibody (4th generation) immunoassay detecting HIV-1, HIV-2 and p24 antigen; positive results are confirmed with an immunoassay that differentiates HIV-1 from HIV-2, and negative or indeterminate confirmations are followed by HIV-1 nucleic acid testing.
• Before treatment, all patients should have a CD4 count, HIV RNA viral load, complete metabolic panel and blood count, and genotypic resistance testing.
• The darunavir-ritonavir regimen suits patients with suspected poor adherence or NRTI resistance because of its high genetic barrier to resistance, but should be avoided when the CD4 count is below 200 or HIV RNA is above 100000.

Overview

This StatPearls chapter (archived; last updated 10 July 2023) reviews antiretroviral therapy for HIV infection. HIV-1 is prevalent worldwide with high virulence and infectivity, while HIV-2 is less virulent and more prevalent in West Africa. Advances in treatment have made the disease manageable and greatly reduced opportunistic infections and progression to AIDS.

Drug classes

Fusion or entry inhibitors block viral entry by inhibiting CCR5 or GP41; nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) prevent transcription of viral RNA into DNA; integrase inhibitors prevent integration of viral DNA into the host genome; and protease inhibitors prevent the protein cleavage needed to form new virions.

Recommended initial regimens

The chapter lists integrase inhibitor-based regimens (dolutegravir/tenofovir disoproxil fumarate/emtricitabine, raltegravir/tenofovir disoproxil fumarate/emtricitabine, dolutegravir/abacavir/lamivudine for HLA-B*5701-negative patients, and elvitegravir-cobicistat with tenofovir disoproxil fumarate or tenofovir alafenamide and emtricitabine) and one protease inhibitor-based regimen (darunavir-ritonavir/tenofovir disoproxil fumarate/emtricitabine). Integrase inhibitor-based regimens have high efficacy, safety and tolerability. Once-daily options include dolutegravir/abacavir/lamivudine and elvitegravir-cobicistat/tenofovir disoproxil fumarate/emtricitabine.

Comorbidity considerations

Regimens containing tenofovir disoproxil fumarate should be avoided in osteoporosis, where dolutegravir/abacavir/lamivudine is a good option. Efavirenz should be avoided in HIV dementia, psychiatric illness and patients on methadone, and dolutegravir in patients at high cardiac risk. Dolutegravir, efavirenz, elvitegravir/cobicistat and protease inhibitors may cause or worsen dyslipidaemia. Pre-exposure prophylaxis is an effective preventive tool for groups at substantial risk.

FAQ

When should antiretroviral therapy be started?

Early in the disease process in all adult and adolescent patients, regardless of CD4 count.

Which tests are needed before starting treatment?

CD4 count, HIV RNA viral load, complete metabolic panel and blood count, and genotypic resistance testing.

When is a protease inhibitor-based regimen preferred?

In patients suspected of poor adherence or with NRTI resistance, because of its high genetic barrier to resistance, unless CD4 is below 200 or HIV RNA above 100000.

Source

Mora Carpio AL, Adil A. Acquired Immune Deficiency Syndrome Antiretroviral Therapy (Archived). In: StatPearls. Treasure Island (FL): StatPearls Publishing; last update 10 July 2023. NCBI Bookshelf NBK436000. Open access. Summary prepared by Medpresso from the original publication; it is not a substitute for the full text or for medical advice.