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Content Update
April 4, 2019
New guideline recommendations regarding prophylaxis in Pneumocystis pneumonia (PCP) and Mycobacterium avium complex (MAC) disease: The U.S. Department of Health and Human Services (DHHS) Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV were updated in early 2019. Among the updates included in this guideline issue were recommendations for when to discontinue prophylaxis (both primary and secondary) for PCP and the decision to initiate primary prophylaxis for MAC. Guidelines now support the discontinuation of PCP prophylaxis (primary or secondary) in patients with an undetectable viral load and a CD4 count between 100 – 200 cells/mm3 for 3-6 months (BII rating). Additionally, the panel no longer recommends primary prophylaxis for MAC in patients able to initiate antiretroviral therapy (ART) immediately regardless of CD4 cell count (AII rating). Healthcare providers should carefully interpret updated guidelines and integrate into clinical practice.
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CHAPTER SUMMARY FROM THE PHARMACOTHERAPY HANDBOOK
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For the chapter in the Wells Handbook, please go to Chapter 40. Human Immunodeficiency Virus Infection.
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KEY CONCEPTS
Infection with human immunodeficiency virus (HIV) occurs through three primary routes: sexual, parenteral, and perinatal. Sexual intercourse, primarily receptive anal and vaginal intercourse, is the most common method for transmission.
HIV infects cells expressing cluster of differentiation 4 (CD4) receptors, such as T-helper lymphocytes, monocytes, macrophages, dendritic cells, and brain microglia. Infection occurs via an interaction between glycoprotein 160 (gp160) on HIV with CD4 (primary interaction) and chemokine coreceptors (secondary interactions) present on the surfaces of these cells.
The hallmark of untreated HIV infection is profound CD4 T-lymphocyte depletion and severe immunosuppression that puts patients at significant risk for infectious diseases caused by opportunistic pathogens. Opportunistic infections (OIs) in settings without access to antiretroviral drugs are the chief cause of morbidity and mortality associated with HIV infection.
The current goal of combination antiretroviral therapy (ART) is to achieve maximal and durable suppression of HIV replication, taken to be a level of HIV-RNA in plasma (viral load) less than the lower limit of quantitation. Another equally important outcome is an increase in CD4 lymphocytes because this closely correlates with the risk for developing OIs.
General principles for the management of OIs include preventing or reversing immunosuppression with ART, preventing exposure to pathogens, vaccination, prospective immunologic monitoring, primary chemoprophylaxis, treatment of acute episodes, secondary chemoprophylaxis, and discontinuation of such prophylaxes following ART and subsequent immune recovery.
Clinical use of antiretroviral agents is complicated by drug–drug interactions. Some interactions are beneficial and used purposely; others may be harmful, leading to dangerously elevated or inadequate drug concentrations. For these reasons, clinicians involved in the pharmacotherapy of HIV infection must exercise constant vigilance and maintain a current knowledge of drug interactions.
Recommendations for the initial treatment of HIV advocate a minimum of three active antiretroviral agents from at least two drug classes. The typical regimen consists of two nucleoside/nucleotide ...