Understanding HIV

HIV, which stands for Human Immunodeficiency Virus, is the virus that causes AIDS (Acquired Immunodeficiency Syndrome). HIV attacks the body’s immune system—its natural defense against infections and disease. Over time, the immune system may become damaged and unable to fight off infections and viruses. HIV causes AIDS when it has significantly damaged the immune system.¹

Though HIV cannot currently be cured, HIV can be treated with a combination of medications. These medications—called antiretrovirals (ARVs)—may help the body fight HIV.¹

The importance of CD4 cells¹

CD4 cells, a type of white blood cell, are an important part of the body’s immune system. HIV attacks and infects the CD4 cells in the immune system. As HIV infects CD4 cells, the number of CD4 cells in the body goes down. As the number of CD4 cells goes down, the immune system gets weaker. Without treatment, this process will continue until the body has very few CD4 cells left, leaving the body at risk of serious conditions such as infections and cancers.

The CD4 cell count¹

The CD4 cell count is a measurement of the amount of CD4 cells in a sample of blood. It can determine how well a patient’s immune system is working. Healthcare professionals (HCPs) will use the results of the CD4 cell count to determine when it’s time to start HIV treatment and to monitor how well HIV therapy is working. CD4 cell count is reported as cells/mm³.

The importance of viral load¹

Viral load is the measurement of the amount of HIV in a sample of a patient’s blood. Viral load is reported as copies per mL. As HIV progresses, the amount of HIV in the blood—the viral load—increases. HCPs use viral load tests to determine when it’s time to start HIV treatment and to monitor how well HIV therapy is working.

For additional information and resources for case managers and other service providers, please visit www.HIVcasemanager.com

Indication: Adults

PREZISTA^®, coadministered with ritonavir (PREZISTA^®/r), and with other antiretroviral agents (ARVs), is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.

This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 controlled Phase 3 trials of 48 weeks' duration in ARV treatment-naïve and treatment-experienced patients and 2 controlled Phase 2 trials of 96 weeks' duration in clinically advanced, treatment-experienced adult patients.

In treatment-experienced adult patients, the following points should be considered when initiating therapy with PREZISTA^®/r:

Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA^®/r
The use of other active agents with PREZISTA^®/r is associated with a greater likelihood of treatment response

Important Safety Information

Drug Interactions

Coadministration of PREZISTA^®/r is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, simvastatin, or sildenafil for the treatment of pulmonary arterial hypertension)
Coadministration of PREZISTA^®/r is also contraindicated with rifampin and products containing St. John’s wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance
Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, salmeterol, telaprevir, and colchicine in patients with hepatic or renal impairment
Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA^®/r. This list of potential drug interactions is not complete

Warnings & Precautions

PREZISTA^® must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA^® with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures
Drug-induced hepatitis (eg, acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA^®/r. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA^®/r. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events

Postmarketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA^®/r therapy has not been established

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA^®/r and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA^®/r treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA^®/r should prompt consideration of interruption or discontinuation of treatment
Severe Skin Reactions: Severe skin reactions (0.4%), accompanied by fever and/or elevations of transaminases in some cases, Stevens-Johnson syndrome (<0.1%), and toxic epidermal necrolysis (postmarketing experience) have been reported in patients receiving PREZISTA^®/r. Discontinue PREZISTA^®/r immediately if signs or symptoms of severe skin reactions develop (including, but not limited to, severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia)

In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of patients receiving PREZISTA^®/r. Discontinuation due to rash was 0.5%
Sulfa Allergy: PREZISTA^® should be used with caution in patients with known sulfonamide allergy
Diabetes Mellitus/Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established
Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy, including PREZISTA^®

Autoimmune disorders (such as Graves disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time of onset is more variable and can occur many months after the initiation of treatment
Resistance/Cross-Resistance: The potential for HIV cross-resistance among protease inhibitors has not been fully explored in PREZISTA^®/r-treated patients

Use in Specific Populations

Hepatic Impairment: PREZISTA^®/r is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment
Pregnancy: PREZISTA^® should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women

Adverse Reactions

In treatment-naïve adult patients, the most common adverse drug reactions (≥5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA^®/r arm through 192 weeks were diarrhea (9%), headache (7%), abdominal pain (6%), and rash (6%)
In treatment-experienced adult patients, the most common adverse drug reactions (≥5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA^®/r arm through 96 weeks were diarrhea (14%), nausea (7%), rash (7%), abdominal pain (6%), and vomiting (5%)
Rash occurred more commonly in treatment-experienced subjects receiving regimens containing PREZISTA^®/r + raltegravir compared to subjects receiving either drug regimen alone. However, rash that was considered drug related occurred at similar rates. These rashes were mild to moderate in severity and did not limit therapy; there were no discontinuations due to rash

This is not a complete list of all adverse drug reactions reported with the use of PREZISTA^®/r.

Please see accompanying full Prescribing Information for more details.