to 700 cells/mm 3 . 29 These measurements are critical for establishing thresholds for the initiation and discontinuation of opportunistic infection prophylaxis. Antiretroviral treatment (ART) HIV infection has become a treatable, chronic medical condition with increasingly near-normal life expectancy when patients receive ART early in the course of their disease or as soon as possible following diagnosis. 28 ART has reduced HIV-related morbidity and mortality at all stages of infection and reduces HIV transmission more potently than any prevention strategy other than celibacy. Maximal and durable suppression of plasma viremia prevents the selection of drug-resistance mutations, improves or at least preserves CD4 cell numbers, and confers substantial clinical benefits, all of which are important treatment goals. 27 Despite the proven benefits of ART, the HIV suppression rate in the US is only 56%––lowest among comparable high-income countries. For example, the United Kingdom and Switzerland have a suppression rate of 84%.30 While the reasons for this low US HIV suppression rate are multifactorial, it is known that it maps to undiagnosed HIV infection and failure to link or retain patients in care. 27 Adherence is a strong predictor of ART effectiveness, and suboptimal medication adherence can produce permanent resistance to an entire class of antiretroviral medications. 29 Linking patients with social services, case management, HIV education, and mental health counseling is critical. When there is reasonable concern that adherence will be a challenge, the clinician and patient should identify and address barriers to treatment (e.g., unstable hous- ing, behavioral health issues, overall patient readi- ness) and consider deferring treatment until there is a greater likelihood of adherence. 29 Current recommendations are to start ART as early as possible, particularly for patients with CD4+ T cell counts <200/mm 3 . Achieving viral suppression currently requires the use of combination ARV regimens that generally include two or three active drugs from two or more drug classes. 27 When initial HIV suppression is not achieved or not maintained, changing to a new regimen with at least two fully active drugs is often required. The increasing number of drugs and drug classes makes viral suppression below the limit of detection an achievable goal in most patients. 27 More than 30 drugs, in 5 classes, have been approved by the FDA for the treatment of HIV infection: 7 ● Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). ● Non-nucleoside reverse transcriptase inhibitors (NNRTIs). ● Protease inhibitors (PIs). ● Integrase strand transfer inhibitors (INSTIs): ○ Entry inhibitors.
In addition, two drugs, ritonavir and cobicistat are used as pharmacokinetic enhancers (or boosters) to improve the pharmacokinetic profiles of PIs and the INSTI, elvitegravir. 27 According to guidelines, the initial ART regimen for a treatment-naive patient generally consists of one or two NRTIs, most frequently or either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/ FTC) or abacavir/lamivudine (ABC/3TC), plus a drug from one of three drug classes: an INSTI, an NNRTI, or a boosted PI. 27 This strategy for initial treatment has resulted in suppression of HIV replication and CD4 cell count increases in most people with HIV. Additional data now support the use of the two- drug regimen dolutegravir/lamivudine (DTG/3TC) for initial treatment of some people with HIV. 27 See the Boxed Copy for Key Considerations and Recommendations for Initial Combination Therapy from the Guidelines (For more detailed information on the drugs used for HIV treatment, access the Guidelines for the Use of Antiviral Agents in Adults and Adolescents with HIV). 27 Key considerations and recommendations for initial combination therapy in antiretroviral-naïve patients 27 ● An antiretroviral regimen for a treatment-naive patient generally consists of two nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a third active drug from one of three drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacokinetic enhancer (also known as a booster; the two drugs used for this purpose are cobicistat and ritonavir). ● Data also support the use of the two-drug regimen, dolutegravir plus lamivudine, for initial treatment. ● Before initiating antiretroviral therapy in a person of childbearing potential, clinicians should discuss the person’s intentions regarding pregnancy and a pregnancy test should be performed. ● The Panel classifies the following regimens as Recommended Initial Regimens for Most People with HIV (in alphabetical order): ○ Bictegravir/tenofovir alafenamide emtricitabine. ○ Dolutegravir/abacavir/lamivudine—only for individuals who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV) coinfection. ○ Dolutegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide [TAF] or tenofovir disoproxil fumarate [TDF]). ○ Dolutegravir/lamivudine, except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when therapy is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available. ● To address individual patient characteristics and needs, the Panel also provides a list of Recommended Initial Regimens in Certain Clinical Situations (See Guidelines).
○ Fusion inhibitor (enfuvirtide). ○ CCR5 antagonist (maraviroc).
○ CD4 post-attachment inhibitor (ibalizumab). ○ gp120 attachment inhibitor (fostemsavir).
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Book Code: CT24CME
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