Genital HIV-1 Shedding With Dolutegravir (DTG) Plus Lamivudine (3TC) Dual Therapy

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

“…When including this variable, the tau-squared were reduced from 1.17 (95% CI 0.33-2.19) to 0.00 (95% CI 0.00-1.11) in the 24 week analysis and from 1.37 (95% CI 0.54-2.15) to 0.00 (95% CI 0.00-1.00) in the 48 week analysis. The inclusion of other variables did not impact the estimates of tau-squared.” Discussion: (page 9) Please provide some references (at least one) for the impact of M184V on viral fitness (this one is of interest for DTG-based regimen: doi: 10.1097/QAD.0000000000001191)(page 9) I think authors should provide some data on VF (%, emerging mutations) during switch from a triple therapy to another one (in order to have an “historical comparator” for dual therapy)(page 10, “In addition, more data on the activity of DTG-based simplified regimens in compartments other than blood are needed.”) There are some references for mono- or dual-therapy in the genital tract (Hocqueloux et al 1 and Gianella et al 2 )and CNS (Doco Lecompte et al 3 )(page 10) Authors should cite recent reports (all communicated at the IAS 2018 in Amsterdam) confirming their conclusions, even though they cannot include them in the analyses: two randomized-controlled clinical trials on DTG monotherapy (Braun et al 4  and Hocqueloux et al 5 ), the extended follow-up of the SWORD trials at week 100 (Aboud et al 6 ) and results of the GEMINI trials (Cahn et al 7  ). References: (references 25 and 28) I think two references (Gantner and Bonijoly) are duplicates (as they are based on the analyze of the same database; Bonijoly et al have included more patients / with longer duration of follow-up than Gantner). …”

“…(page 10, “In addition, more data on the activity of DTG-based simplified regimens in compartments other than blood are needed.”) There are some references for mono- or dual-therapy in the genital tract (Hocqueloux et al 1 and Gianella et al 2 )and CNS (Doco Lecompte et al 3 )…”

Patient-centered Care and Treatment in HIV Infection

“…The dual dolutegravir plus lamivudine or emtricitabine regimen combines a drug with high antiviral potency, long half-life, high genetic barrier to resistance and tolerability (dolutegravir) with one with a good tolerability (lamivudine or emtricitabine). In addition, interactions with other drugs are limited, and dual therapy with dolutegravir and lamivudine does not appear to increase genital shedding of HIV-1 [5], hence should not increase the risk of sexual transmission of the virus. The concern regarding the reduced “forgiveness” (i.e., the possibility that viral replication increases) should patients be not fully adherent was highly mitigated in Diaco's patients by the fact that they were followed for many years by the same physician, who had established a very good relationship with them and whom they trusted.…”

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

“…In the MONODO study, all patients had an undetectable plasma HIV viral load at week 24 on DTG maintenance monotherapy, whereas only one had a detectable viral load in the cerebrospinal fluid 21 . Moreover, levels of HIV-RNA in the genital tract on DTG monotherapy 41 and on DTG-3TC 42 were comparable to those on standard cART. However, these results were based on a very small sample of patients and data from individuals on simplified, DTG-based therapies are lacking.…”

“…When including this variable, the tau-squared were reduced from 1.17 (95% CI 0.33-2.19) to 0.00 (95% CI 0.00-1.11) in the 24 week analysis and from 1.37 (95% CI 0.54-2.15) to 0.00 (95% CI 0.00-1.00) in the 48 week analysis. The inclusion of other variables did not impact the estimates of tau-squared.” Discussion: (page 9) Please provide some references (at least one) for the impact of M184V on viral fitness (this one is of interest for DTG-based regimen: doi: 10.1097/QAD.0000000000001191) (page 9) I think authors should provide some data on VF (%, emerging mutations) during switch from a triple therapy to another one (in order to have an “historical comparator” for dual therapy) (page 10, “In addition, more data on the activity of DTG-based simplified regimens in compartments other than blood are needed.”) There are some references for mono- or dual-therapy in the genital tract (Hocqueloux et al 1 and Gianella et al 2 )and CNS (Doco Lecompte et al 3 ) (page 10) Authors should cite recent reports (all communicated at the IAS 2018 in Amsterdam) confirming their conclusions, even though they cannot include them in the analyses: two randomized-controlled clinical trials on DTG monotherapy (Braun et al 4 and Hocqueloux et al 5 ), the extended follow-up of the SWORD trials at week 100 (Aboud et al 6 ) and results of the GEMINI trials (Cahn et al 7 ). References: (references 25 and 28) I think two references (Gantner and Bonijoly) are duplicates (as they are based on the analyze of the same database; Bonijoly et al have included more patients / with longer duration of follow-up than Gantner).…”