Letter from Gilead: Update on HIV
PrEP Research Among Cisgender Women
I am pleased to provide an update on progress to date with the Phase 3 clinical trial of Descovy (emtricitabine 200mg/tenofovir alafenamide 25mg tablets) for PrEP® in young women and adolescent girls, as we work to deliver additional prevention options for all those at risk for HIV.
Gilead is committed to generating data informing the use of Descovy for PrEP in individuals at risk for HIV from receptive vaginal sex - a population currently excluded from the approved indication for this prevention medicine. As this use is investigational and the efficacy in this population is not yet known, we are eager to initiate this study, and look forward to further understanding Descovy’s potential as a prevention option for individuals at risk of HIV-1 from receptive vaginal sex.
As a result of COVID-19, the current public health climate has unsurprisingly forced some postponements of trial activities; however, this delay will allow us to incorporate pending input from the South African Health Products Regulatory Authority into final study protocol filings. Our most recent meeting with leading South African and Ugandan advocates took place last week. We anticipate that study modifications may be necessary as key stakeholders provide additional insights. We will continue to share updates with you as the study design and protocol are finalized.
We greatly appreciate the input received to date from our global community advisory group, which is comprised of diverse voices reflecting equitable community representation. Consultations with this group have influenced nearly every aspect of our study of Descovy for PrEP in young women and adolescent girls - from determining how demographic data will be collected, to improving the consent process, to better balancing data collection with participant burden.
Beyond Descovy for PrEP, we recognize there is interest in our ongoing efforts to research and develop other product candidates for HIV treatment and prevention. We are committed to ensuring diversity across these research programs while balancing the urgent need for additional treatment options - particularly among highly treatment-experienced individuals with multi-drug resistance. We are in the process of planning a community meeting dedicated solely to an update on these research and development programs.
Gilead is making progress toward our goal of gender parity in HIV trials because of the engagement of dedicated community partners and stakeholders. We welcome and appreciate your input and look forward to continuing dialogue with you on this priority.
Please take the time to read the approved U.S. Indication and Important Safety Information for Descovy for PrEP provided below; in addition to the limitation of use, the product label contains a Boxed Warning for the risks of drug resistance with use of Descovy for PrEP in undiagnosed early HIV infection and for post-treatment exacerbation of hepatitis B.
Senior Vice President, HIV and Emerging Viruses
DESCOVY for PrEP is indicated in at-risk adults and adolescents (≥35 kg) to reduce the risk of sexually acquired HIV-1 infection, excluding individuals at risk from receptive vaginal sex. HIV-1-negative status must be confirmed immediately prior to initiation.
• Limitation of Use: DESCOVY FOR PrEP is not indicated in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
• DESCOVY FOR PrEP must be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.
• Severe acute exacerbations of hepatitis B have been reported in patients infected with hepatitis B virus (HBV) who discontinued products containing FTC and/or TDF and may occur with discontinuation of DESCOVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients with HBV who discontinue DESCOVY. If appropriate, anti-hepatitis B therapy may be warranted.
• DESCOVY FOR PrEP is contraindicated in patients with unknown or positive HIV status.
Warnings and precautions
• Comprehensive management to reduce risks:
⋅ Use DESCOVY FOR PrEP to reduce the risk of HIV-1 infection as part of a comprehensive strategy that includes adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).
⋅ HIV-1 risk factors: Behavioral, biological, or epidemiologic HIV-1 risk factors may include, but are not limited to: condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network.
⋅ Reduce STI risk: Counsel on the use of STI prevention measures (e.g., consistent and correct condom use, knowledge of partner’s HIV-1 viremic status, regular testing for STIs).
⋅ Reduce potential for drug resistance: Only prescribe DESCOVY FOR PrEP to patients confirmed to be HIV negative immediately prior to initiation, at least every 3 months while taking DESCOVY, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in patients with undetected HIV-1 infection who are taking only DESCOVY because DESCOVY alone is not a complete regimen for treating HIV-1.
⋅ Some HIV tests may not detect acute HIV infection. Prior to initiating DESCOVY FOR PrEP, ask patients about potential recent exposure events. If recent (<1 month) exposures are reported or suspected, or symptoms of acute HIV infection (e.g., fever, fatigue, myalgia, skin rash) are present, confirm HIV-negative status with a test approved by the FDA for use in the diagnosis of acute HIV infection.
⋅ If HIV-1 infection is suspected or if symptoms of acute infection are present while taking DESCOVY FOR PrEP, convert the DESCOVY FOR PrEP regimen to a complete HIV treatment regimen until HIV-negative status is confirmed by a test approved by the FDA for use in the diagnosis of acute HIV infection.
⋅ Counsel on adherence: Counsel patients to strictly adhere to daily dosing, as efficacy is strongly correlated with adherence. Some patients, such as adolescents, may benefit from more frequent visits and counseling.
• New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. Do not initiate DESCOVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue DESCOVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients (see Dosage and Administration section).
• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
• Most common adverse reactions (≥2%) in the DESCOVY FOR PrEP clinical trial were diarrhea, nausea, headache, fatigue, and abdominal pain.
• Prescribing information: Consult the full Prescribing Information for DESCOVY for more information, warnings, and potentially significant drug interactions, including clinical comments.
• Metabolism: Drugs that inhibit P-gp can increase the concentrations of tenofovir alafenamide (TAF), a component of DESCOVY. Drugs that induce P-gp can decrease the concentrations of TAF, which may lead to loss of efficacy.
• Drugs affecting renal function: Coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.
Dosage and administration
• Dosage: One tablet taken once daily with or without food.
• HIV screening: Test for HIV-1 infection immediately prior to initiating, at least every 3 months during use, and upon diagnosis of an STI (see Warnings and Precautions section).
• HBV screening: Test for HBV infection prior to or when initiating DESCOVY.
• Renal impairment and monitoring: Not recommended in patients with creatinine clearance (CrCl) <30 mL/min. Prior to or when initiating DESCOVY, and during use on a clinically appropriate schedule, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.
Full Prescribing Information for DESCOVY, including BOXED WARNING, is available at Gilead.com.