Dolutegravir And Lamivudine Combination For The Treatment Of HIV-1 Infection

Figures & data

Figure 1 DTG molecular structure (adapted from PubChem).²²

Figure 2 3TC molecular structure (adapted from PubChem).²⁷

Table 1 Summary Of Clinical Trials – DTG/3TC For Treatment-Naive Individuals

Authors	Title	Study Design	Subjects on DTG/3TC vs3-Drug Regimen	HIV RNA< 50 Copies Per mL, DTG/3TC vs 3-Drug Regimen (% FDA Snapshot)	Mean CD4 Count Increase (cells/µL)	Discontinuation Due To AEs DTG/3TC vs3-Drug Regimen (%)	Virologic Failure (%)	Treatment Emergent Resistance, DTG/3TC vs 3-Drug Regimen
Cahn et al^Citation34	PADDLE	Proof of concept (Phase I)	20/NA	90(48 week)	267	0	5	None
Taiwo et al^Citation35	ACTG A5353	Phase II	120/NA	90(24 week)	NA	0	<1%	M184V and R263R/K in 1 subject
Cahn et al^Citation36	GEMINI 1 and 2	Phase III	719/722	91(48 week)	NA	1/2	2/3 (virologic non-response)	None

Table 2 Select Adverse Effects Reported From Phase III Trials At Week 48

Adverse Effects	DTG/3TC (%)	3-Drug Regimen (%)
Any adverse effect
Headache	10	10
Diarrhea	9	11
Nasopharyngitis	8	11
Upper respiratory tract infection	8	6
Pharyngitis	5	4
Back pain	5	4
Nausea	4	7
Insomnia	4	6
Drug-related adverse effect	18	24
Serious adverse events Drug related serious adverse events	7 1	8 1
Adverse events leading to discontinuation of treatment or withdrawal from study	2	2
Discontinuation due to drug-related adverse events	1	1

Table 3 Changes In Renal Biomarkers In GEMINI Trials

Parameters	Two-Drug Regimen	Three-Drug Regimen	P-value
Mean change in serum creatinine (mmol/mL)	+10.4	+13.5	0.0001
GFR from creatinine CKD-EPI (mL/min per 1.73 mm^3)	−12.1	−15.5	0.0001
Protein creatinine ratio of week 48 to baseline (g/mol)	+0.87	+1.03	0.0001

Table 4 Changes In Lipid Profiles In GEMINI Studies

Adjusted Mean Change (mmol/L)	Two-Drug Regimen	Three-Drug Regimen	P-value
Total cholesterol	+0.32	−0.15	0.0001
HDL cholesterol	+0.15	+0.02	0.0001
LDL cholesterol	+0.17	−0.14	0.0001
Triglycerides	+0.03	−0.08	0.0457
Ratio of total cholesterol to HDL cholesterol	−0.12	−0.24	0.0182

PubChem. Dolutegravir. [online]. 2019 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Dolutegravir-sodium Accessed 81, 2019.

 Google Scholar

PubChem. Lamivudine. [online]. 2019 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/60825#section=Structures Accessed 81, 2019

 Google Scholar

Cahn P, Rolon MJ, Figueroa MI, et al. Dolutegravir-Lamivudine as initial therapy in HIV-1 infected ARV-naïve patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir 3TCivudinE) study. J Int AIDS Soc. 2017;20:1. doi:10.7448/IAS.20.01.21678

 Web of Science ®Google Scholar

Taiwo B, Zheng L, Stefanescu A. et al. ACTG A5353: A pilot study of dolutegravir plus lamivudine for initial treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected participants with HIV-1 RNA <500000 copies/mL. Clin Infect Dis. 2018;66(11):1689–1697. doi:10.1093/cid/cix108329253097

 PubMed Web of Science ®Google Scholar

Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicenter, double-blind, randomized, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143–155. doi:10.1016/S0140-6736(18)32462-030420123

 PubMed Web of Science ®Google Scholar