- Infection with human immunodeficiency virus (HIV) occurs through three primary modes: 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 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 antiretroviral therapy (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.
- Current 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 analogs with either a protease inhibitor (PI; pharmacokinetically enhanced by coadministration with a CYP3A inhibitor), a nonnucleoside reverse transcriptase inhibitor, or an integrase strand transfer inhibitor (InSTI).
- Inadequate suppression of viral replication allows HIV to select for antiretroviral-resistant HIV variants, a major factor limiting the ability of antiretroviral drugs to inhibit virus replication. Current recommendations for treating drug-resistant HIV include choosing at least two drugs (preferably three) to which the patient’s virus is susceptible. Susceptibility can be assessed using either (virtual) genotypic or phenotypic resistance testing.
- The reduction of viral load with ART lowers the risk of transmission to others. Additionally, prophylaxis with antiretroviral agents in at-risk persons lowers HIV acquisition risk.
- The longer life span conferred by antiretroviral treatment has given rise to other medical issues. First, a wide spectrum of complications associated with older age have become common, some of which are adverse effects from antiretroviral drugs. Second, hepatitis C virus (HCV) coinfection is an important cause of morbidity and mortality. Medical management of these contemporary HIV complications is constantly evolving.
On completion of the chapter, the reader will be able to:
Characterize the modes, ...