Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Corneal hypoxia and hypercapnia during contact lens wear.

Restriction of both oxygen influx to the cornea and carbon dioxide efflux from the cornea by contact lenses results in adverse tissue changes. We measured the extent of hypoxia and hypercapnia at the corneal surface of 10 human volunteers during static, dynamic (blinking), and closed-eye wear of hydrogel and nonhydrogel contact lenses of different gas transmissibilities. During open-eye wear, hypoxia and hypercapnia are lower beneath lenses of higher oxygen and carbon dioxide transmissibilities, respectively (p less than 0.001). Blinking plays a significant role in alleviating corneal hypoxia (p less than 0.05), but not hypercapnia, during lens wear. In the absence of lenses, the gaseous tensions at the anterior corneal surface during eye closure were: pO2 = 37.4 +/- 20.9 mm Hg and pCO2 = 39.3 +/- 3.1 mm Hg. Closed-eye lens wear resulted in greater levels of hypoxia and hypercapnia that were directly correlated with lens transmissibility (p less than 0.001). These data form the basis of models for predicting adverse tissue changes during contact lens wear and suggest prophylactic and therapeutic clinical strategies for alleviating lens-induced hypoxia and hypercapnia.