MK 677 for Sleep Optimization and Growth Hormone Release
This guide takes a deeper dive into how MK-677 supports sleep optimization and boosts GH levels, and what kind of physiological changes researchers have observed in MK 677 before and after comparisons.
MK-677 is classified as a growth hormone secretagogue, meaning it signals the pituitary gland to secrete more of your body's own growth hormone. Unlike synthetic GH injections, which introduce external hormones into the system, MK-677 works with your endocrine system to elevate natural production. That's one of the reasons it's often explored as a gentler alternative with longer-lasting benefits.
What makes MK-677 unique is its oral availability and long half-life of around 24 hours, allowing for once-a-day dosing while maintaining stable blood levels. This is particularly helpful for supporting GH release throughout the sleep cycle, especially during the deep stages of rest when tissue repair and muscle recovery peak.
MK-677's effect on sleep isn't anecdotal. Clinical trials have shown it increases rapid eye movement (REM) and deep-wave sleep duration. This matters because: REM sleep contributes to memory consolidation and cognitive recovery.
contributes to memory consolidation and cognitive recovery. Deep-wave sleep is when the body releases the highest volume of natural growth hormone.
Better sleep doesn't just make you feel rested—it supports more effective protein synthesis, insulin sensitivity, and cellular recovery. These benefits are why MK-677 is often incorporated into recovery-focused research protocols and lifestyle optimization studies.
Across various anecdotal logs and experimental research notes, MK-677 users have reported dramatic improvements in several key areas over the course of 8–12 weeks. When evaluating MK 677 before and after case studies, these trends frequently emerge: Fragmented sleep or early waking
Stalled muscle recovery
Lower perceived energy throughout the day
Decreased appetite in some individuals
Plateau in lean mass gain despite training Deeper, longer sleep cycles with fewer disturbances
Enhanced lean muscle growth
Boosted appetite and nutrient absorption
Fuller muscle look with improved vascularity
Noticeable fat reduction when paired with cardio or caloric control
While experiences vary, these shifts often begin within the first two weeks of consistent MK-677 administration and continue to improve with regular use and supportive training.
Growth hormone plays a crucial role in how well the body repairs and grows muscle after resistance training. But its release is closely tied to the quality of sleep.
By enhancing both, MK-677 helps set off a positive feedback loop: Deeper sleep → More GH release More GH release → Better tissue repair and recovery Faster recovery → Increased training volume and strength Increased training volume → More hypertrophy and metabolic change
This dynamic makes MK-677 ideal for off-season muscle building phases, post-surgery healing, or even general wellness protocols where tissue support is essential.
One lesser-known benefit of MK-677 is its influence on ghrelin—the 'hunger hormone.' By binding to ghrelin receptors, MK-677 not only increases appetite but also promotes better digestion and nutrient uptake, both of which are essential during mass-building phases or when trying to overcome a plateau.
More calories consumed and utilized efficiently mean more opportunity for recovery and growth, especially when supported by optimal hormone levels during rest.
Though MK-677 is non-suppressive (it doesn't shut down testosterone), some side effects have been reported in longer research trials, especially when exceeding recommended dosing protocols: Mild water retention or bloating
Increased appetite to a fault in some cases
Temporary insulin resistance if paired with poor diet
Vivid dreams (due to REM sleep extension)
For most researchers, these are manageable with proper nutrition, cycle planning, and lifestyle adjustments. Always remember—consistent dosing and observation are key to responsible MK-677 research.
While there's no universal dosing guide for research purposes, many studies document 10–25 mg/day as the effective range for MK-677. Here's a typical outline: Beginners: 10 mg/day for 8 weeks
10 mg/day for 8 weeks Intermediate: 15–20 mg/day for 12 weeks
15–20 mg/day for 12 weeks Advanced: 25 mg/day with adjusted caloric intake and monitoring
Due to MK-677's long half-life, once-a-day dosing is enough. Evening doses are often preferred to align with natural GH pulses during sleep.
While MK-677 performs well alone, it's also commonly stacked with SARMs like: RAD-140: To amplify lean mass and strength
To amplify lean mass and strength LGD-4033: For dense size and hard muscle
For dense size and hard muscle GW-501516: For fat-burning and endurance during a cut
When stacking, always begin with conservative doses, especially for first-time research protocols, and extend cycle breaks to ensure long-term hormonal stability.
Q1: Can MK-677 really improve sleep quality?Yes. Research has shown longer REM and deep sleep stages, which support natural GH release and overall recovery.
Q2: Is MK-677 a steroid or a SARM?No, it is neither. MK-677 is a growth hormone secretagogue, not a steroid or a selective androgen receptor modulator.
Q3: How long before I notice changes?Most users report deeper sleep and appetite increases within the first week. Physical changes like fullness and muscle gain show by week 3–4.
Q4: Will I lose gains after stopping MK-677?If training, diet, and sleep are maintained, much of the lean mass and recovery gains can be retained. Appetite may normalize after discontinuation.
Q5: Can women use MK-677 for recovery?Yes. It's non-hormonal and well-tolerated in both men and women, though dosing should be individualized.
For those looking to optimize sleep and amplify the benefits of natural growth hormone, MK-677 stands out as a reliable, non-invasive tool in research-based performance strategies. From improved REM cycles to enhanced tissue repair and better nutrient utilization, its benefits go beyond just muscle gain.
When used responsibly, it can be a cornerstone of any recovery-focused or muscle-building protocol especially for those who understand that progress begins while you sleep.
TIME BUSINESS NEWS
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Yahoo
16-07-2025
- Yahoo
Japanese warship used in WWII found on Pacific seafloor: See photos
A team of scientists discovered a Japanese naval destroyer for the first time since it was sunk by American troops in World War II. Researchers exploring islands off the coast of the Solomon Islands in the Pacific Ocean located the Imperial Japanese Navy destroyer Teruzuki, the Ocean Exploration Trust organization announced in a press release July 12. Teruzuki — a Japanese word meaning "shining moon" or "illuminated moon" — was a 440 feet-long warship designed for screening aircraft carriers from aerial attacks. It was stationed off the island of Guadalcanal in the Solomon Islands, a nation in the south Pacific north of Australia, to protect supply ships before being attacked and sunk by American troops in December 1942, OET said. 'I feel so lucky to see this ship. The fact that we have not seen Teruzuki in over 80 years underscores the importance of recording maritime heritage now,' said Hiroshi Ishii, a member of the research team involved in the discovery, in the release. In the early hours of December 12, 1942, American patrol boats attacked the convoy, striking Teruzuki in the stern with a pair of Mk-8 torpedoes. The detonation broke the ship's rudder, disabling the ship and engulfing it in flames. Most of its crew were rescued or swam to shore, but nine men were killed as Teruzuki sank, according to OET. Through the discovery of the ship, researchers were able to piece together exactly what happened during the attack, OET said. A 62-foot segment of the ship's stern was found littered with depth charges, disproving a long-held theory that such weapons sealed the ship's fate, OET said. Instead, the broken rudder impaired the vessel and sparked fires, causing it to sink. A group of scientists using remotely operated vehicles to explore an area of seafloor discovered the Teruzuki, OET said. Remotely operated vehicles are underwater machines used to scan ocean depths while being operated by someone at the water's surface, according to the National Oceanic and Atmospheric Administration. According to OET, because Japanese naval vessel plans were kept highly secret during the war, no historical images of Teruzuki exist. Melina Khan is a national trending reporter for USA TODAY. She can be reached at This article originally appeared on USA TODAY: Japan's WWII destroyer Teruzuki found in Pacific: See photos
Business Wire
14-07-2025
- Business Wire
Merck to Initiate Phase 3 Trials for Investigational Once-Monthly HIV Prevention Pill
BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of the EXPrESSIVE Phase 3 clinical trials, evaluating the safety and efficacy of MK-8527, an investigational once-monthly, oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) for HIV pre-exposure prophylaxis (PrEP). The EXPrESSIVE-11 (MK-8527-011, NCT 07044297) trial will evaluate the safety and efficacy of MK-8527 among people with greater likelihood of HIV-1 exposure in 16 countries and will begin enrolling in August 2025. In collaboration with the Gates Foundation, the EXPrESSIVE-10 (MK-8527-010) trial will evaluate the safety and efficacy of MK-8527 in women and adolescent girls in sub-Saharan Africa and will begin enrolling in the next few months. 'According to UNAIDS, 1.3 million people acquired HIV in 2023, highlighting the continued need for new PrEP options like our investigational once-monthly, oral PrEP candidate MK-8527, especially among women in sub-Saharan Africa and men who have sex with men, who experience disproportionately high rates of HIV,' said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 'Our collaboration with the Gates Foundation will help us explore the potential of MK-8527 to contribute to global efforts to reduce the number of HIV infections and help support opportunities to accelerate access around the world.' The decision to initiate the Phase 3 clinical trial program was supported by the results of a double-blind, multicenter, Phase 2 trial (MK-8527-007, NCT 06045507) examining the safety and pharmacokinetics of MK-8527. The study enrolled 350 participants, 18–65 years of age, with low likelihood of HIV-1 exposure, who were randomized 2:2:2:1 to receive MK-8527 (3, 6, or 12 mg) or placebo once monthly for six months. In the trial, the rates of adverse events were similar among those in the MK-8527 arms and those in the placebo arm, and no clinically meaningful changes were seen in laboratory tests, including total lymphocyte and CD4 T-cell counts. The pharmacokinetics of MK-8527 and MK-8527-TP, the active form of MK-8527, support the continued development of MK-8527 as an oral, once-monthly option for PrEP. Results from the Phase 2 trial were highlighted in the opening press conference for IAS 2025, the 13th International AIDS Society Conference on HIV Science in Kigali, Rwanda, on Monday, July 14, at 15:30 – 16:30 CAT, titled 'Breakthroughs Amid Crisis: The Future of HIV Innovation.' These research findings will be further detailed in a late-breaker oral session on Wednesday, July 16, at 12:15 – 13:15 CAT. 'Scientific advances against HIV have brought us further than ever imagined and are ushering in a new era in HIV prevention,' said Trevor Mundel, president of global health at the Gates Foundation. 'With only 18% of global PrEP need currently met, there is a clear and urgent need for options like MK-8527 that may offer the ability to prevent infection. These Phase 3 trials are a key step toward translating progress into longer-acting options that could help turn the tide on HIV.' In the EXPrESSIVE-10 trial, the International Clinical Research Center (ICRC) within the University of Washington Department of Global Health, in partnership with the University of Alabama at Birmingham, will receive grant funding from the Gates Foundation to support ICRC's collaboration with 31 clinical research trial sites in Kenya, South Africa, and Uganda; sites will inform and engage communities and recruit, enroll, and follow women who participate in the EXPrESSIVE-10 trial. Merck will be the trial sponsor, gaining regulatory and customs approvals, and providing operational expertise and resources for management of the trials. The Gates Foundation will also provide support for global community advisory groups, which will offer insight into community perspectives on a monthly PrEP pill, participant recruitment materials and strategies, and cultural considerations for these trials. Separately, the Gates Foundation will provide grant funding for EXPrESSIVE-11 to support the establishment of a community advisory group and the development of recruiting and retention materials only. About the EXPrESSIVE MK-8527 Phase 3 Clinical Trial Program The EXPrESSIVE-11 trial (MK-8527-011, NCT 07044297) is a randomized, active-controlled study enrolling 4,390 sexually active people who could benefit from PrEP across trial sites in 16 countries. The primary objective of the study is to evaluate the efficacy, safety, and tolerability of once-monthly oral MK-8527 compared to daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as assessed by the incidence rate per year of adjudicated HIV-1 infections. The trial will begin enrolling in August 2025. The EXPrESSIVE-10 trial (MK-8527-010) is a randomized, active-controlled study enrolling 4,580 sexually active women aged 16 to 30 in Kenya, South Africa, and Uganda. The primary objective of the study is to evaluate the efficacy, safety, and tolerability of once-monthly oral MK-8527 compared to daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as assessed by the incidence rate per year of adjudicated HIV-1 infections. The study will begin enrolling in the next few months. About MK-8527 MK-8527 is being evaluated as a potential once-monthly oral prevention option for HIV-1. MK-8527 inhibits reverse transcriptase through multiple mechanisms of action, including inhibition of translocation and delayed chain termination. For an overview of Merck's complete HIV treatment and prevention clinical development program, please click here. Merck's Commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV, leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage their HIV and to help prevent HIV, with the goal of reducing the growing burden of HIV worldwide. We want to ensure people are not defined by HIV, and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at helping to end the HIV epidemic for everyone. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube, and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the 'company') includes 'forward-looking statements' within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2024 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (
Business Wire
10-07-2025
- Business Wire
U.S. FDA Accepts New Drug Application for Merck's Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection
BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA). 'Merck has been at the forefront of HIV research for more than 35 years and we are pleased to continue our work to innovate and deliver new options that aim to meet the needs of the HIV community,' said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 'The health needs of people living with HIV often change over time – whether it's managing comorbidities or navigating complex medication regimens. We believe DOR/ISL, if approved, will represent an important new complete regimen option designed to help meet their diverse needs.' The NDA is based on findings at Week 48 of two pivotal Phase 3 clinical trials (MK-8591A-051 and MK-8591A-052) where DOR/ISL was demonstrated to be non-inferior to baseline antiretroviral therapy (bART) in the open-label trial MK-8591A-051 and non-inferior to bictegravir/emtrictabine/tenofovir alafenamide i [BIC/FTC/TAF (50mg/200mg/25mg)] in the double-blind trial MK-8591A-052. Across both trials, the safety profile of DOR/ISL was generally comparable to comparator baseline antiretroviral regimens in trial MK-8591A-051 and BIC/FTC/TAF in trial MK-8591A-052. Data from these trials were presented during the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco. About the Phase 3 Trial MK-8591A-051 MK-8591A-051 is a Phase 3, open-label, randomized, active-controlled clinical trial evaluating the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed using ART. The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n=366) or continued bART (n=185), stratified by bART regimen. The median age of participants was 51 years; 39.7% were assigned female sex at birth, 45.4% were Black or African American, and 14.5% were Hispanic or Latine. At baseline, 64.2% were treated with an InSTI-based regimen, 30.3% with an NNRTI-based regimen, and 5.4% with a protease inhibitor (PI)-based regimen, with median duration on current ART of 3.8 years (IQR 2.0-6.3). About the Phase 3 Trial MK-8591A-052 MK-8591A-052 is a Phase 3, double-blind, randomized, active-controlled clinical trial to evaluate the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50mg/200mg/25mg). The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n=342) or continued treatment with BIC/FTC/TAF (n=171). The median age of participants was 47 years; 21.4% were assigned female sex at birth, 30.8% were Black or African American, and 22.8% were Hispanic or Latine. The median duration of BIC/FTC/TAF treatment prior to trial enrollment was 3.4 years (IQR 2.0-5.0). About Islatravir (MK-8591) and Merck's HIV Research Islatravir (MK-8591), Merck's investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA, resulting in delayed chain termination. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in the treatment regimens based on its potency and resistance profile. In addition to the MK-8591A-051 and MK-8591A-052 trials, ongoing Phase 3 trials of daily DOR/ISL (100mg /0.25mg) include MK-8591A-053 in people with HIV who had not previously received treatment (treatment-naïve), and MK-8591A-054 evaluating open-label DOR/ISL (100 mg/0.25 mg) in individuals who participated in earlier Phase 3 trials of DOR/ISL (100 mg/0.75 mg). Islatravir in combination with Gilead's lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1, and islatravir in combination with our company's investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2 development as an oral once-weekly treatment. Merck's commitment to researching NRTTIs includes MK-8527, an investigational, novel oral, once-monthly NRTTI candidate that is in Phase 2 development for HIV-1 pre-exposure prophylaxis (PrEP). For an overview of Merck's HIV treatment and prevention clinical development program, please click here. Merck's Commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage their HIV and to help prevent HIV, with the goal of reducing the growing burden of infection worldwide. We want to ensure people are not defined by HIV, and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at helping to end the HIV epidemic for everyone. Indications and usage for PIFELTRO ® (doravirine) and DELSTRIGO ® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. Selected Safety Information Warning: Posttreatment Acute Exacerbation of Hepatitis B Virus (HBV) for DELSTRIGO All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted. Contraindications PIFELTRO and DELSTRIGO are contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John's wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Warnings and Precautions Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO or DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. New or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF. Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min. Bone Loss and Mineralization Defects In clinical trials in adults living with HIV, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults are unknown. Immune Reconstitution Syndrome Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Drug Interactions Because DELSTRIGO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended. If DELSTRIGO is coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart). Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions. Dosage and Administration/Specific Populations Renal Impairment Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min. Adverse Reactions The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%). By week 96 in DRIVE-FORWARD, 2% of adult participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication. By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication. In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated. In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium. The safety of DELSTRIGO in virologically-suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history. Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of participants in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of participants had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of participants in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen. Pregnancy/Breastfeeding There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the 'company') includes 'forward-looking statements' within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2024 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (
