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The association of intraocular efavirenz concentrations and HIV-1 viral load among persons with HIV.
Journal of Acquired Immune Deficiency Syndromes : JAIDS 2024 March 26
OBJECTIVE: Efavirenz (EFV) is commonly used in combination antiretroviral therapy (cART). However, in our previous study, many persons living with human immunodeficiency virus (HIV) exhibited ocular complications despite undergoing effective cART. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies.
DESIGN: Observational, retrospective study.
METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy (PPV) were enrolled between January 2019 and August 2022. The patients were divided into two groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during PPV. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) .
RESULTS: The median age of the enrolled patients was 48 years (interquartile range [IQR], 32.25-53.25), including 12 men and 2 females. Median vitreous and plasma EFV concentrations were 141.5 (IQR, 69.63-323.75) and 2,620 ng/mL (1,680-4,207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0,04 vs 0.12, p = 0.042) .ConclusionsThe vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be due to poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with retinal detachment, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit the HIV-1 replication in ocular tissues.
DESIGN: Observational, retrospective study.
METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy (PPV) were enrolled between January 2019 and August 2022. The patients were divided into two groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during PPV. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) .
RESULTS: The median age of the enrolled patients was 48 years (interquartile range [IQR], 32.25-53.25), including 12 men and 2 females. Median vitreous and plasma EFV concentrations were 141.5 (IQR, 69.63-323.75) and 2,620 ng/mL (1,680-4,207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0,04 vs 0.12, p = 0.042) .ConclusionsThe vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be due to poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with retinal detachment, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit the HIV-1 replication in ocular tissues.
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