Aim
Dolutegravir (DTG; S/GSK1349572) is under clinical development as a once daily, unboosted integrase inhibitor for the treatment of HIV infection. The effect of DTG on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and creatinine clearance (CLcr) was evaluated in 34 healthy volunteers.
Methods
Subjects received DTG 50 mg (once daily or twice daily) or placebo for 14 days. GFR was measured by iohexol plasma clearance, ERPF was assessed by para‐aminohippurate plasma clearance and CLcr was measured by 24 h urine collection.
Results
All treatments were generally well tolerated. A modest decrease (10–14%) in CLcr was observed, consistent with clinical study observations. DTG 50 mg once daily and twice daily had no significant effect on GFR or ERPF compared with placebo over 14 days in healthy subjects.
Conclusions
These findings support in vitro data that DTG increases serum creatinine by the benign inhibition of the organic cation transporter 2, which is responsible for tubular secretion of creatinine.
Data demonstrating non-inferiority of switching to ABC/DTG/3TC versus continuing current ART support ABC/DTG/3TC as an option when considering switch regimens in HIV-1-infected adults with stable viral suppression.
The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE
BackgroundWhile advances in treatment have dramatically improved the lives of people living with HIV (PLHIV), a number of important unmet needs remain. We conducted an international survey of PLHIV to explore their treatment experience and emotional challenges of ART.MethodsQualitative in-depth interviews were performed with PLHIV to identify key hypotheses. A steering group (led by community members) developed the survey tool which was fielded online from November 2016 to July 2017 in 8 high-income countries in North America (NA), Europe, and Australia. A mixed sampling/recruitment approach was used to ensure a broad cross-section of PLHIV. Respondents were screened for eligibility prior to receiving access to the online survey.Results1111 PLHIV were surveyed (74% male, 41% 35–49 years; 39% from NA). The majority (98%) were currently taking ARTs with 53% taking a single tablet regimen. Of those on treatment, 87% were satisfied with their current ART. Overall, results for NA respondents were similar to the global results. Many participants reported emotional challenges associated with their daily HIV treatment experience: 66% agreed taking ART every day was a reminder of their HIV status; 25% agreed being tied to a daily medication limited their day-to-day life; and 29% agreed they felt stressed and under pressure to take their HIV medication at the right time every day. Those not “open” about their HIV status were more likely to feel stressed by their medication and felt that it limited them. 37% of participants frequently or quite often hid their HIV medication to avoid revealing their HIV status, particularly amongst those who reported experiencing stigma or high emotional impact of HIV. 89% felt that advances in treatment will improve their quality of life. Reducing long-term adverse effects of ART and lowering dosing frequency were considered the most important areas for improvement; this was similar across demographics such as country, age, and gender.ConclusionIn this international survey of PLHIV, despite overall satisfaction with current ART, significant emotional burden and daily impact of treatment persists. PLHIV consider the reduction of long-term adverse effects and dosing frequency important areas for improving ART.Disclosures
All authors: No reported disclosures.
In HIV-1-infected patients, virological failure can occur as a consequence of the mutations that accumulate in the viral genome that allow replication to continue in the presence of antiretrovirals (ARVs). The development of treatment-emergent resistance to an ARV can limit a patient's options for future therapy, prompting the need for ARV regimens that are resilient to the emergence of resistance. The genetic barrier to resistance refers to the number of mutations in an ARV's therapeutic target that are required to confer a clinically meaningful loss of susceptibility to the drug. The emergence of resistance can be affected by pharmacological aspects of the ARV, including its structure, inhibitory quotient, therapeutic index, and pharmacokinetic characteristics. Dolutegravir (DTG) has demonstrated a high barrier to resistance, including when used in a two-drug regimen (2DR) with lamivudine (3TC). In the GEMINI-1 and GEMINI-2 studies, DTG +3TC was noninferior to DTG + emtricitabine/tenofovir disoproxil fumarate in treatment-naive participants, with similar proportions achieving HIV-1 RNA <50 copies/mL through 96 weeks. Furthermore, in the TANGO study, virological suppression was maintained at 48 weeks after switching to DTG +3TC from a tenofovir alafenamide (TAF)-based regimen compared with continuing a TAF-based regimen. Most other 2DRs with successful outcomes compared with three-drug regimens have been based on protease inhibitors (PIs); however, this class is associated with adverse metabolic effects and drug-drug interactions. In this review, we discuss the barrier to resistance in the context of a 2DR in which a boosted PI is replaced with DTG +3TC.
Background: To investigate antiviral potency of the 2-drug regimen (2DR) dolutegravir plus lamivudine vs the 3-drug regimen (3DR) dolutegravir plus tenofovir disoproxil fumarate/emtricitabine, we performed a post-hoc analysis assessing antiviral response rates in the phase III GEMINI-1 and GEMINI-2 studies by baseline viral load (VL).Setting: One hundred ninety-two centers in 21 countries.Methods: Treatment-naive HIV-1-infected participants with screening VL #500,000 copies/mL were randomized 1:1 to oncedaily dolutegravir plus lamivudine or dolutegravir plus tenofovir disoproxil fumarate/emtricitabine. Median change from baseline was determined for log 10 -transformed VL in the overall study population and the subpopulation with baseline VL .100,000 copies/mL. Proportion of participants achieving plasma VL ,50 copies/mL (Snapshot algorithm) or ,40 copies/mL (Abbott RealTime HIV-1 assay) and target not detected was assessed through week 48 by baseline VL. Time to viral suppression was determined (nonparametric Kaplan-Meier method).Results: For 293 participants with baseline VL .100,000 copies/mL, median change from baseline at week 4 was 23.38 and 23.40 log 10 copies/mL in the 2DR and 3DR groups, respectively; reduction was sustained throughout 48 weeks. Time to VL ,50 copies/mL was longer in participants with baseline VL .100,000 copies/mL than the overall study population (57 [week 8] vs 29 days [week 4]) and similar between the 2DR and 3DR groups. Proportion of participants with VL ,50 or ,40 copies/mL and target not detected was similar between groups, irrespective of baseline VL, at all tested visits throughout 48 weeks.
The publisher would like to report an error that appeared in a recently published article [1]. The y-axis label in Figure 3A has been corrected as of 13 September 2017 and should read 'Median increase in CD4 + T-cell counts, cells/mm 3 '. The accompanying footnote has also been amended and the correct version is shown. The authors apologize for this error.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.