Early clinical experience of dolutegravir in an HIV cohort in a larger teaching hospital

Abstract

Dolutegravir (DTG) is the third HIV integrase inhibitor (INI) available for prescription in Belfast since July 2014. It has shown high virological efficacy in both treatment-naïve and -experienced patients. We carried out a retrospective case chart analysis of HIV-1-positive adults commenced on DTG between July 2014 and September 2015. Patients were identified from records as either treatment-naïve or antiretroviral therapy (ART) experienced. Outcomes included: (1) virological response (HIV-1 RNA viral load at 0, 4, 8 and 12 weeks), (2) immunological response (CD4+ cell count at 0, 4, 8 and 12 weeks) and (3) tolerability (side effects and discontinuation). The main exclusion criteria were patients transferring care already established on DTG from other treatment centres or inadequate follow-up information (defined as attendance at <50% of clinical and serological follow-up visits). One hundred and fifty-seven commenced DTG out of 823 patients on ART; 106 (68%) were switched to DTG from another regimen, and 51 (32%) were ART-naïve. One naïve and 14 treatment-experienced patients were excluded from the analysis due to failure to attend clinical follow-up. Analysis of HIV-1 RNA viral load (HIV-1 VL) was divided into three groups: 50 new starters, 68 suppressed at switch and 24 not suppressed at switch. New starters: Baseline median HIV-1 RNA VL 71,259 copies/mL (19,536-196,413); 73% were virally undetectable (HIV-1 RNA VL <70 copies/mL) by week 4. Switching patients: Of those with an HIV-1 RNA undetectable viral load prior to switching, two were detectable with a mean viral load of 443,730 copies/mL after four weeks. Of the 24 patients detectable at switch (median HIV-1 VL 2212 [311-43,467]), 10 were detectable after four weeks. For those with a recordable viraemia, the median HIV-1 VL reduced to 376 (220-1181). At week 12, four patients were detectable with a median VL of 12,390 (567-52,285). Overall, 56 (35%) reported side effects; 40 (25%) reported either difficulty with low mood, anxiety or sleep disturbance. Sixteen (10%) discontinued DTG, with 13 (8%) due to intolerable side effects. DTG is a useful drug in naïve or switch patients. It has the potential to effectively suppress the viral load within the first four weeks of treatment and thus reduces infectiousness. Within the cohort, DTG was generally well tolerated but side effects such as low mood, anxiety and sleep disturbance were high, with 8% of patients discontinuing treatment.

Increased Dolutegravir Peak Concentrations in People Living With Human Immunodeficiency Virus Aged 60 and Over, and Analysis of Sleep Quality and Cognition

“…In pre-marketing trials, DTG demonstrated favorable safety and tolerability profiles, with a <2% discontinuation rate secondary to any adverse events (AEs), comparable to raltegravir and superior to efavirenz [8,9]. However, contrasting real-life data reveal unexpectedly higher rates (7-15%, median time 72 days) [10][11][12][13][14], most commonly due to insomnia/sleep disturbances and other neuropsychiatric (NP) AEs (up to 8%), regardless of prior neuropsychiatric history, thereby implicating a potentially neurotoxic effect of DTG [14][15][16][17][18]. Comparison studies suggest that NP-AEs are commoner with DTG than other InSTIs [11,12,16].…”

Safety, Tolerability, and Efficacy of Generic Dolutegravir-containing Antiretroviral Therapy Regimens Among South Indian Human Immunodeficiency Virus-infected Patients

“…Of those who underwent ART substitution, the most common first-line regimen was TDF plus 3TC plus efavirenz (EFV) (75%); TDF plus 3TC plus ritonavir-boosted atazanavir (28.1%) and darunavir plus raltegravir plus ritonavir (25%) were the most common second-and third-line regimens, respectively. 24 (14,80) 15 (12,18) 16 Overall, kidney function remained stable at 6 months follow-up, with median creatinine at initiation of 0.9 (IQR, 0.7-1.1), and 1.0 (IQR, 0.8-1.2) and 0.9 (IQR, 0.85-1.1) at 6 and 12 months, respectively. No patients had an increase in liver enzymes as per the National Institutes of Health/Division of Acquired Immuno Deficiency Syndrome grading scale.…”

Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting

“…5,14,15 Some observational studies have also shown good virologic outcomes in suppressed patients switching to RAL, [16][17][18] one study in patients switching to EVG, 9 and one in patients switching to DTG. 19 One cohort study reported low failure rates over two years after switching while suppressed to an INSTI-based regimen, including RAL, DTG, and EVG, though it did not compare INSTI agents. 10 Some studies have shown good virologic outcomes on RAL or DTG in heterogeneous groups comprising both suppressed and unsuppressed patients.…”