integrase strand transfer inhibitors
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Abstract Multi-class high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multi-class resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only one drug class, the integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype.

Background: In the past, HIV infection was associated with weight loss due to metabolic wasting. Now with early initiation of antiretroviral therapy (ART) an increasing number of patients are being classified as overweight/ obese both prior to initiation and during the course of ART. Certain integrase strand transfer inhibitors (INSTIs) have been associated with weight gain in the adult population, but data in the pediatric population is lacking. This study explores the association of ART with an INSTI backbone and changes in weight and body mass index (BMI) in children with perinatal HIV who are followed in the HIV clinic at Riley Hospital. Methods: We performed a retrospective review of 59 patients with perinatally acquired HIV from 2016 to 2021. Weight, BMI, z-score, blood pressure (BP) percentiles, and lipid panels were recorded from the patients’ most recent visit. BMI and BP percentiles were compared between patients on Bictegravir, Dolutegravir, and Elvitegravir. For patients currently on an INSTI-backbone ART regimen, BMI was compared before and up to 5 years after INSTI initiation. Results: In our cross-sectional analysis between patients on Bictegravir, Dolutegravir, and Elvitegravir there was no significant difference in BMI (p=0.859), systolic BP percentile (p=0.188), or diastolic BP percentile (p=0.541). In our longitudinal analysis, we observed a significant increase in BMI over 3 years compared to pre-INSTI initiation (p=0.049). In addition, we observed an upwards trend with patients on Bictegravir (p=0.094) and Elvitegravir (p=0.121). Conclusion/Impact: Our study suggests that ART regimens with an INSTI backbone are associated with greater increases in BMIs. Our study is limited by a small n, but provides pilot data to direct future studies. It also illustrates that emphasis on healthy body weight maintenance may be necessary when patients are placed on ART regimens with INSTI backbones.

Abstract Background Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs). Methods This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. Results Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P <  0.001). Furthermore, the proportion of patients on polypharmacy was significantly higher in those with PDDIs than in those without PDDIs (81.0% vs. 26.7%, P <  0.001). Conclusions The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment.

The current study evaluated the progress of continuum healthcare for patients living with human immunodeficiency virus (HIV) infection from Cluj County in two moments, 2016 and 2020, and compared the results to the Fast-Track targets (FTTs) proposed by the Joint United Nations Programme (UNAIDS) on HIV/AIDS. By the end of 2020, 368 out of 385 confirmed HIV-positive patients from Cluj County were under surveillance in our center, representing almost 95% of the patients living with HIV and knowing their diagnosis, compared to 87.9% in 2016. Nearly 97% of those in active follow-up from Cluj County were under antiretroviral therapy (ART) in 2020, compared to 89% in 2016. The number of virally suppressed patients from those under ART was almost 94% in 2020, compared to 82.7% in 2016, and the increase is observed regardless of the ART regime. A shift towards integrase strand transfer inhibitors, with a higher efficacy, fewer adverse effects, and fewer drug interactions, is observed, which could contribute to the decrease in HIV transmission.

In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies.