HIV Therapy Flashcards
Currently Available Antirteroviral Classes
• Reverse Transcriptase Inhibitors
- Nucleoside/nucleotide analogues
- Non-nucleoside analogues
- Protease Inhibitors
- Attachment Inhibitors
- Integrase Strand Transfer Inhibitors
NRTIs
NNRTIs
Nucleoside Monophosphate - TDF
Nucleoside Monophosphate - TAF
Protease Inhibitors
INSTIs
HIV 1 Attachment Inhibitors
Fusion Inhibition
Ibalizumab
Fostemsavir
When to Start
What to Start
•INSTI + 2 nucleotide (nucleoside) analogues
OR
•Protease Inhibitor + 2 nucleotide (nucleoside) analogues
Goals of Antiretroviral Therapy
- Within 6 weeks, plasma HIV RNA should have declined by >1 log
- By six months, HIV RNA should be undetectable (<50 copies/ml)
- CD4 cell count will rise with suppression of HIV RNA
The Problem of Viral Latency
- ART suppresses all actively replicating virus BUT
- There are reservoirs of non-replicating HIV-1 that are not susceptible to ART
- When ART is stopped, these reservoirs cause new active replication
- Recent data suggest that this reservoir is 60-fold larger than previously thought
If plasma HIV RNA [] copies/mL, transmission of HIV-1 does not appear to occur.
If plasma HIV RNA <20 copies/mL, transmission of HIV-1 does not appear to occur.
Preexposure prophylaxis (PrEP)
•Providing therapy prior to an event to block the occurrence of that event
- Malaria prophylaxis
- Birth control
•Efficacy depends on
- Risk of that event occurring
- Effectiveness of the prevention
•In HIV infection, it is providing antiretroviral therapy (ART) to uninfected, at risk individuals
What to provide & time to efficacy
•Only TDF/FTC once daily
- TAF/FTC recently was approved
- Do not use any other antiretroviral
- Do not use other than daily dosing - iPrEP not currently recommended
- Maximum concentrations in rectum takes up to 7 days; 20 days for blood and cervical-vaginal tissue
Metabolic & skeletal complications of HIV therapy
• Body composition
- Lipoatrophy
- Visceral fat accumulation
• Dyslipidemia
- Hypertriglyceridemia
- Hypercholesterolemia
- ↓HDL
• Abnormal glucose metabolism
- Insulin resistance
- Impaired glucose tolerance
- Diabetes mellitus
• Cardiovascular disease
-Accelerated atherosclerosis
- Lactic Acidosis
- Bone disorders
- Osteopenia
- Osteoporosis
- Osteonecrosis
Pneumocystis pneumonia
- Most common opportunistic infection in HIV
- Risk ↑ when peripheral blood CD4 <200/µl
- Presents as progressive dyspnea, fever
- Chest radiograph: diffuse interstitial process
- Arterial blood gas: ↓pO2, ↓pCO2
- Bronchoalveolar fluid demonstrates cysts and trophozoites; fluorescent antibody staining useful
Oral candidiasis
- Overgrowth of Candida on mucosal surfaces
- Presents initially in the oral cavity
- Erythematous candidiasis
- Pseudomembranous canididiasis
• With marked immunodeficiency, may involve the esophagus
- Interferes with swallowing and nutrition
Immune Response Inflammatory Syndrome
- Over-reaction to smoldering infection when CD4 count rises due to antiretroviral treatment
- May be particularly severe in CNS infections
- Mycobacterium tuberculosis, M. avium, CMV, cryptococcosis are most common
- Approach
- in some cases, delay initiation of antiretroviral therapy
• cryptococcal and tuberculous meningitis
- treat specific infection
- ± corticosteroids
Labs to obtain prior to starting antiretroviral therapy
