What are the side effects of antiviral regimens for HIV (Human Immunodeficiency Virus) prophylaxis, including Tenofovir Disoproxil Fumarate (TDF) plus Emtricitabine (FTC), and Dolutegravir (DTG) plus TDF or Tenofovir Alafenamide (TAF) plus FTC?

From the Guidelines

The most recent and highest quality study suggests that antiviral regimens for HIV prophylaxis, including Tenofovir Disoproxil Fumarate (TDF) plus Emtricitabine (FTC), and Dolutegravir (DTG) plus TDF or Tenofovir Alafenamide (TAF) plus FTC, have distinct side effect profiles that should be carefully considered in clinical practice. The side effects of these regimens can be broken down as follows:

• TDF plus FTC can cause nausea, headache, dizziness, and fatigue in the first few weeks of treatment, as well as gastrointestinal symptoms like diarrhea, vomiting, and abdominal pain 1.
• Long-term use of TDF may lead to decreased kidney function and reduced bone mineral density, requiring regular monitoring of kidney function and consideration of bone health 1.
• FTC is generally well-tolerated but can cause skin discoloration, particularly on the palms and soles.
• The newer regimen of DTG plus TDF or TAF plus FTC has a different side effect profile, with DTG potentially causing insomnia, headache, and neuropsychiatric symptoms like anxiety or depression in some individuals 1.
• TAF has fewer kidney and bone effects compared to TDF but may be associated with weight gain and lipid abnormalities, as noted in the 2020 recommendations of the International Antiviral Society-USA panel 1. Some key points to consider when prescribing these regimens include:
• Monitoring kidney function and bone health regularly, especially in patients taking TDF 1.
• Advising patients to take these medications with food to reduce gastrointestinal symptoms.
• Reporting persistent or severe side effects to their healthcare provider immediately.
• Considering the potential for weight gain and lipid abnormalities with TAF, as well as the potential for neuropsychiatric symptoms with DTG 1.

From the FDA Drug Label

The most common adverse reactions (incidence greater than or equal to 10%, all grades) included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Table 4 provides the treatment-emergent adverse reactions (Grades 2 to 4) occurring in greater than or equal to 5% of subjects treated in any treatment group Fatigue 9%, Depression 9%, Nausea 9%, Diarrhea 9%, Dizziness 8%, Upper respiratory tract infections 8%, Sinusitis 8%, Rash event 7%, Headache 6%, Insomnia 5%, Nasopharyngitis 5%, Vomiting 2% Laboratory Abnormalities: Laboratory abnormalities observed in Trial 934 were generally consistent with those seen in previous trials (Table 5). Any ≥ Grade 3 Laboratory Abnormality 30%, Fasting Cholesterol (>240 mg/dL) 22%, Creatine Kinase(M: >990 U/L)(F: >845 U/L) 9%, Serum Amylase (>175 U/L) 8%, Alkaline Phosphatase (>550 U/L) 1%, AST(M: >180 U/L)(F: >170 U/L) 3%, ALT(M: >215 U/L)(F: >170 U/L) 2%

The side effects of antiviral regimens for HIV prophylaxis, including Tenofovir Disoproxil Fumarate (TDF) plus Emtricitabine (FTC), and Dolutegravir (DTG) plus TDF or Tenofovir Alafenamide (TAF) plus FTC, are:

• Gastrointestinal symptoms: diarrhea, nausea, vomiting, abdominal pain
• Neurological symptoms: headache, dizziness, depression, insomnia, abnormal dreams
• Dermatological symptoms: rash
• Laboratory abnormalities: elevated creatine kinase, serum amylase, fasting cholesterol, and triglycerides
• Other symptoms: fatigue, upper respiratory tract infections, sinusitis, nasopharyngitis 2

From the Research

Side Effects of Antiviral Regimens for HIV Prophylaxis

The side effects of antiviral regimens for HIV prophylaxis, including Tenofovir Disoproxil Fumarate (TDF) plus Emtricitabine (FTC), and Dolutegravir (DTG) plus TDF or Tenofovir Alafenamide (TAF) plus FTC, have been studied in several clinical trials.

• Gastrointestinal Side Effects: Daily PrEP with TDF-FTC has been associated with initial gastrointestinal side effects, such as diarrhea and nausea 3.
• Renal and Bone Safety: TDF has been linked to renal decline and bone mineral density decrease, whereas TAF has shown improved renal safety and bone mineral density compared to TDF 4, 5.
• Weight Gain: Significant weight gain has been observed in participants taking TAF or TDF with FTC and DTG, with a median weight gain of 1.7 kg and 7.1 kg, respectively 4, 6.
• Changes in Rectal Microbiota: Daily PrEP with TDF-FTC has been shown to reduce Streptococcus and increase Erysipelotrichaceae in rectal microbiota, which may be associated with gut microbiome dysbiosis 3.
• Adverse Events: The most common adverse events reported in clinical trials include diarrhea, nausea, and headache, with a low rate of treatment-related serious adverse events and discontinuations due to adverse events 6, 7.

Comparison of TAF and TDF

Studies have compared the safety and efficacy of TAF and TDF in combination with FTC and DTG.

• Efficacy: TAF and TDF have shown similar efficacy in preventing HIV-1 infection, with TAF demonstrating non-inferiority to TDF 4, 5.
• Safety: TAF has been associated with improved renal safety and bone mineral density compared to TDF, with a lower risk of renal adverse events and discontinuations due to adverse events 4, 5.

Dolutegravir-Based Regimens

Dolutegravir-based regimens, including DTG with TAF or TDF and FTC, have been studied in clinical trials.

• Efficacy: DTG with TAF or TDF and FTC has shown high efficacy in treating HIV-1 infection, with a high proportion of participants achieving viral suppression 6, 7.
• Safety: DTG with TAF or TDF and FTC has been well-tolerated, with a low rate of treatment-related serious adverse events and discontinuations due to adverse events 6, 7.