The INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015;373:795-807 The TEMPRANO ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med 2015;373:808-22 Lee FJ, Amin J, Carr A. Efficacy of initial antiretroviral therapy for HIV-1 infection …
Nicholas Medland1, Vincent Cornelisse2, Don Smith3 The Kirby Institute, University of NSW, Sydney, NSW Kirketon Road Centre, Sydney, NSW The Albion Centre, Surry Hills, Sydney, NSW Last reviewed: November 2019 Antiretroviral drug classes The six classes of antiretroviral drugs currently licensed for use in Australia are: Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs); Non-nucleoside reverse transcriptase inhibitors …
The four regimens currently recommended for the initial treatment of most people with HIV infection combine a two-drug NRTI backbone with a third antiretroviral drug from the INSTI class, as follows: Dolutegravir/abacavir/lamivudine (if HLA-B*5701 negative) Dolutegravir + emtricitabine/tenofovir alafenamide (tenofovir AF) or tenofovir disoproxil fumarate (tenofovir DF) Raltegravir + emtricitabine/tenofovir AF or tenofovir DF Bictegravir/emtracitabine/tenofovir AF …
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NRTIs inhibit HIV RNA-dependent DNA polymerase (reverse transcriptase) by acting as structural analogues for thymidine or adenosine when DNA is reverse transcribed inside cells leading to premature DNA chain termination and inhibition of viral replication. All NRTIs also have the potential to inhibit human intracellular DNA polymerases, including those necessary for mitochondria to replicate. Mitochondrial …
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The NNRTI class includes nevirapine (NVP), efavirenz (EFV), rilpivirine (RPV), etravirine (ETR) and doravirine (DOR). NNRTIs bind directly to the reverse transcriptase enzyme and block the RNA-dependent and DNA-dependent polymerase activities by causing a disruption of the enzyme’s catalytic site. This reduces enzyme activity and diminishes viral replication. Importantly NNRTIs are not active against HIV-2 …
HIV protease inhibitors (PIs) inhibit HIV-1 and HIV-2 proteases and prevent cleavage of the gag-pol polyprotein during maturation of the newly formed viral particle. This results in the production of immature, non-infectious virus. There are currently seven licensed PIs: atazanavir (ATV), darunavir (DRV), fosamprenavir (FOS), lopinavir (coformulated with ritonavir [LPV/r]), ritonavir (RTV), saquinavir (SQV) and …
Integrase strand transfer inhibitors (INSTIs) prevent the integration of HIV DNA into the nucleus of the host cell. Elvitegravir is only available as part of an FDC tablet with tenofovir or emtricitabine and cobicistat, unlike raltegravir and dolutegravir which are available as individual medications. Dolutegravir is also available co-formulated with abacavir and lamivudine or rilpivirine …
Two antiretroviral drugs have been developed that act as entry inhibitors, forming two separate classes; the fusion inhibitor enfuvirtide and the CCR5-receptor antagonist maraviroc. Fusion inhibitors Enfuvirtide (also known as T-20) is a synthetic 36-amino acid peptide analogue. It binds to HIV-1 gp41, interrupting the fusion reaction and preventing the virus from infecting the host cell. Enfuvirtide, …
New antiretroviral agents in the existing classes are being developed with the aim of producing drugs with more favourable toxicity profiles and activity against drug-resistant HIV. These include a new CCR5 inhibitor cenicriviroc (Phase III) that also has activity blocking CCR2, thereby dampening inflammation. There is also a monoclonal antibody directed against CCR5 (PRO 140) …
Antiretroviral drug regimens that should not be offered at any time are shown in Table 8. Table 8. Antiretroviral drug regimens that should not be offered at any time (see the DHHS guidelines for exceptions[2]) Antiretroviral drug regimen Rationale Monotherapy with NRTIs Inferior virological activity plus rapid development of resistance Dual-NRTI regimens Inferior virological activity …
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