Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as TDF
Truvada · 6 trials · 4 indications
Number of HIV infections defined by the presence of HIV ribonucleic acid (RNA) in plasma through study completion (an average of two years) in the event-driven F/TAF arm.
Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.
The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (\> 19 vs ≤ 19 IU/L for females; \> 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.
| Arm | Type | Description |
|---|---|---|
| Event-driven PrEP with TDF/FTC | ACTIVE_COMPARATOR | Participants randomly assigned to the event-driven TDF/FTC arm will be instructed to take a loading dose of two single tablets containing coformulated TDF/FTC (300/200mg) 2 to 24 hours before sexual intercourse, followed by a third pill 24 hours after the first drug intake and a fourth pill 24 hours later. In case of daily sexual intercourses, they will be instructed to take one pill per day until the last sexual intercourse, then to take the two post-exposure pills. |
| Event-driven PrEP with TAF/FTC | EXPERIMENTAL | Participants randomly assigned to the event-driven TAF/FTC arm will be instructed to take one single tablet containing coformulated TAF/FTC (25/200mg) with or without food 2 to 24 hours before sexual intercourse followed by a second pill 24 hours after the first drug intake. In case of daily sexual intercourses, they will be instructed to take one pill per day until the last sexual intercourse and then a last pill 24 hours later. |
| E/C/F/TAF | EXPERIMENTAL | Participants will switch from tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or 3TC plus a third agent to E/C/F/TAF and will receive treatment for 48 weeks. |
| Remain current regimen | ACTIVE_COMPARATOR | Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent. |
| Tenofovir DF | EXPERIMENTAL | TDF plus placebo to match FTC/TDF |
| FTC/TDF | EXPERIMENTAL | FTC/TDF plus placebo to match TDF |
| TDF-TDF | EXPERIMENTAL | TDF plus ADV placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC tablet) to their treatment regimen in the open-label period. |
| ADV-TDF | ACTIVE_COMPARATOR | ADV plus TDF placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period. |
| TDF + placebo | PLACEBO_COMPARATOR | Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 1 mg | EXPERIMENTAL | Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 2 mg | EXPERIMENTAL | Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 4 mg | EXPERIMENTAL | Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| Name | Type | Description |
|---|---|---|
| TDF/FTC 300mg/200mg fixed-dose combination tablets | DRUG | Event-driven dosing regimen |
| TAF/FTC 25mg/200mg fixed-dose combination tablets | DRUG | Event-driven dosing regimen. |
| E/C/F/TAF | DRUG | 150/150/200/10 mg FDC tablet administered orally once daily |
| TDF | DRUG | 300 mg tablet administered orally once daily |
| FTC | DRUG | 200 mg capsule administered orally once daily |
| FTC/TDF | DRUG | 200/300 mg tablet administered orally once daily |
| 3TC | DRUG | Tablet administered orally |
| Third agent | DRUG | Third agent may include one of the following regimens: lopinavir+ritonavir (LPV/r; Kaletra®), atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®), ATV + cobicistat (COBI;Tybost®) (or ATV/COBI FDC), DRV + RTV, darunavir (DRV; Prezista®) + COBI (or DRV/COBI FDC), fosamprenavir (FPV; Lexiva®) + RTV , saquinavir (SQV; Invirase®; Fortovase®) + RTV, efavirenz (EFV;Sustiva®), rilpivirine (RPV;Edurant®), nevirapine (NVP;Viramune®), etravirine (ETR;Intelence®), raltegravir (RAL; Isentress®), elvitegravir (EVG) + COBI, or dolutegravir (DTG;Tivicay®) Drug classes: * Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV, and SQV * Pharmacokinetic enhancer: COBI * Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR * Integrase inhibitors: RAL and DTG |
| TDF Placebo | DRUG | TDF placebo tablet administered orally once daily |
| FTC/TDF Placebo | DRUG | FTC/TDF placebo tablet administered orally once daily |
| ADV | DRUG | 10 mg tablet administered orally once daily |
| ADV placebo | DRUG | Tablet administered orally once daily |
| Vesatolimod | DRUG | Tablets administered orally once a week (every 7 days) for 12 doses |
| Placebo | DRUG | Placebo administered orally once a week (every 7 days) for 12 doses |
Inclusion Criteria: * Male at birth age ≥ 18 years old * Reporting having sex with men * Negative 4th generation HIV-1 and HIV-2 test * Reporting condomless anal sex with men not more often than two days during the previous month and able to plan their sexual activity * Risk of HIV acquisition base...