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Chapter 93
Antiviral Agents II: Drugs for HIV
Infection and Related Opportunistic
Infections
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Drugs for HIV Infection and Related
Opportunistic Infections
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Human immunodeficiency virus is a retrovirus
(HIV-1 and HIV-2)
HIV has RNA as genetic material
Uses reverse transcriptase to convert RNA
into DNA and integrase to Insert its DNA into
ours
Target cells: CD4 T cells (helper
lymphocytes)
Transmission – blood and body fluids
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Virus present in all body fluids
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Human Immunodeficiency Virus
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Promotes immunodeficiency by killing CD4 T
lymphocytes
Difference between HIV and AIDS
Global epidemic
Standard antiretroviral therapy (ART)
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Reduced AIDS deaths by 72%
HAART – highly active antiretroviral therapy
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Fig. 93-1. Structure of the human immunodeficiency virus.
Note that HIV has two single strands of RNA, and that each strand is associated with a molecule
of reverse transcriptase. (gp 41 = glycoprotein 41, gp120 = glycoprotein 120.)
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Fig. 93-2. Replication cycle of the human immunodeficiency virus.
See text for description of events. (CCR5 = CCR5 co-receptor, CD4 = CD4 receptor,
CXCR4 = CXCR4 co-receptor, dsDNA = double-stranded DNA, gp120 = glycoprotein 120,
mRNA = messenger RNA, ssDNA = single-stranded DNA, ssRNA = single-stranded RNA.)
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Classification of Antiretroviral Drugs
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Five types of antiretroviral drugs
Inhibit enzymes required for HIV
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Reverse transcriptase inhibitors
Integrase inhibitors
Protease inhibitors
Block viral entry into cells
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Fusion inhibitors
CCR5 antagonists
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Nucleoside Reverse Transcriptase
Inhibitors (NRTIs)
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Zidovudine (Retrovir)
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Adverse effects
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Inhibits HIV replication by suppressing synthesis
of viral DNA
Anemia and neutropenia
Lactic acidosis/hepatic steatosis (rare)
Gastrointestinal effects
CNS reactions
Drug interactions
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Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs)
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Differ from the NRTIs in structure and
mechanism of action
NNRTIs bind to the active center of reverse
transcriptase and cause direct inhibition
Active as they are administered
See Table 93-4
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Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs)
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Efavirenz (Sustiva)
Nevirapine (Viramune)
Delavirdine (Rescriptor)
Etravirine (Intelence)
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NNRTIs
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Efavirenz (Sustiva)
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Preferred agent for treating HIV
Only NNRTI recommended for first-line
therapy for HIV infection
Drug interactions
Adverse effects
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Teratogenicity
Transient adverse CNS effects in 50% of patients
 Rash
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Protease Inhibitors
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Among the most effective antiretroviral drugs
available
Used in combination with NRTIs – can reduce
viral load to an undetectable level
Resistance
Drug interactions
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P450 inhibitors
 P450 inducers
 P450 substrates
 Herb interactions
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Protease Inhibitors
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Adverse effects
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Hyperglycemia/diabetes
Fat malredistribution
Hyperlipidemia
Reduced bone density
Hepatotoxicity
Increased bleeding in hemophiliacs
Reduced bone mineral density
Elevation of serum transaminase
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Protease Inhibitors
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Lopinavir/ritonavir (Kaletra)
Ritonavir (Norvir)
Indinavir (Crixivan)
Saquinavir (Invirase, Fortovase)
Nelfinavir (Viracept)
Amprenavir (Agenerase)
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Protease Inhibitors
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Fosamprenavir (Lexiva)
Atazanavir (Reyataz)
Tipranavir (plus Ritonavir)
Darunavir (plus Ritonavir)
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HIV Integrase Strand Transfer
Inhibitors
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Raltegravir (Isentress) approved in 2007
First and only member of this new class of
antiretroviral drugs
Adverse side effects
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Diarrhea, nausea, fatigue, headache, and itching
FDA Pregnancy Risk Category C
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Enfuvirtide (Fuzeon)
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HIV fusion inhibitor
Widely known as T-20
First and only HIV fusion inhibitor
Blocks entry of HIV into CD4 T cells
BID subQ dosing costs $20,000 a year
Adverse effects
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Injection site reactions, pneumonia, and
hypersensitivity reactions
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Maraviroc (Selzentry)
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CCR5 antagonist
Approved in 2007
Indicated only for combined use with other
antiretroviral drugs in treatment-experienced
adults infected with CCR5-tropic HIV-1 strains
that are resistant to multiple drugs
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Laboratory Monitoring for HIV
Infection and Drug Therapy
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Viral load (plasma HIV RNA)
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Best measurement for predicting clinical outcome
CD4 T-cell counts
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HIV Treatment in Pregnancy
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Same principles that guide antiretroviral
therapy in nonpregnant adults
Mother-to-child transmission HIV
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Occurs primarily during labor and delivery
Risk for transmission can be greatly reduced by
ART, which minimizes maternal viral load
The same general principles also apply to
children
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Treatment
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Prophylactic drugs can reduce the risk for
infection after accidental exposure
Advanced HIV disease may need
prophylactic antibiotics because of decreased
CD4 T cell counts
PCP most common opportunistic infection
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Trimethoprim plus sulfamethoxazole
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