Ocular Lens Density in HIV Patients With Low Nadir CD4 Count
Ocular Lens Density in HIV Patients With Low Nadir CD4 Count
Background: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated.
Methods: Case–control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression.
Results: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count.
Conclusions: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection.
Antiretroviral therapy (ART) has reduced mortality among HIV-infected people, largely because of the prevention of AIDS-related events but also because of a decrease in non–AIDS-related events and deaths. However, it is now of concern that ART cohorts are aging. In the United States, for example, it is estimated that by 2015, more than 50% of the HIV-infected population will be more than 50 years of age. This trend is becoming apparent in sub-Saharan Africa where there is an expanding cohort of HIV-infected individuals who are aged more than 50. Patients receiving ART are thought to be at increased risk of age-related non-AIDS morbidity and mortality compared with HIV-seronegative persons. Several of these conditions are classically associated with the normal aging process but occur at an earlier age in HIV-infected persons compared with age-matched HIV-seronegative individuals. Thus, HIV infection may be associated with accelerated senescence, and the increased risk of systemic age-related morbidities in HIV-infected people has frequently been found to be associated with nadir CD4 count and ART duration.
Cataracts are opacities of the intraocular lens, and the prevalence of lens opacities increases exponentially with age. They are a leading cause of blindness and visual impairment worldwide. Individuals with cataract have an increased mortality risk than those without, even after adjusting for known confounders. The human lens is considered an ideal tissue for studying macromolecular aging, as biochemical mechanisms in lens proteins may reflect aging processes elsewhere in the body. In the context of lens opacities and HIV, 2 possible scenarios exist. First, although the prevalence of HIV-related opportunistic ocular infections [such as cytomegalovirus (CMV) retinitis] has decreased, the introduction and scale-up of ART has led to immune recovery phenomena. This may manifest in the eye as "immune recovery uveitis" (IRU). It is characterized by ocular inflammation after ART initiation and can lead to cataract formation. Second, if premature aging does occur in HIV-infected individuals, an increased risk of ocular age-related conditions such as cataract might be expected. To date, there is minimal information about age-related eye conditions and the possibility of accelerated aging in HIV-infected patients, particularly within sub-Saharan Africa.
The Pentacam (Oculus, Wetzlar, Germany) is a 360-degree rotating noncontact camera that provides a rapid and precise 3 dimensional (3D) view of the lens, cornea, and anterior chamber. The Pentacam uses a blue light-emitting diode (wavelength 475 nm) to image the anterior eye segment, capturing 25 single-slit images in 2 seconds while rotating around the eye from 0 to 180 degrees. The instrument acquires data points that provide a representative image of the whole lens. The Pentacam contains integral software that can automatically quantify lens "density" by measuring the light-scattering intensity of the lens layers. This provides a form of objective lens opacity (cataract) grading. The objective of the study was to assess differences in lens density using the Pentacam in a cohort of HIV-infected individuals in comparison with an age-matched and a sex-matched HIV-seronegative group. Our study hypotheses were that (a) HIV-infected individuals will have a greater lens density compared with sex- and age-matched HIV-seronegative individuals and (b) low nadir CD4 count at ART initiation is associated with an increased risk of higher lens density. Our study was conducted in Cape Town, South Africa, with recruitment of cases and controls from the same communities to reduce the likelihood of differential risk exposure in line with the recommendation for careful study design when investigating premature aging in HIV.
Abstract and Introduction
Abstract
Background: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated.
Methods: Case–control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression.
Results: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count.
Conclusions: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection.
Introduction
Antiretroviral therapy (ART) has reduced mortality among HIV-infected people, largely because of the prevention of AIDS-related events but also because of a decrease in non–AIDS-related events and deaths. However, it is now of concern that ART cohorts are aging. In the United States, for example, it is estimated that by 2015, more than 50% of the HIV-infected population will be more than 50 years of age. This trend is becoming apparent in sub-Saharan Africa where there is an expanding cohort of HIV-infected individuals who are aged more than 50. Patients receiving ART are thought to be at increased risk of age-related non-AIDS morbidity and mortality compared with HIV-seronegative persons. Several of these conditions are classically associated with the normal aging process but occur at an earlier age in HIV-infected persons compared with age-matched HIV-seronegative individuals. Thus, HIV infection may be associated with accelerated senescence, and the increased risk of systemic age-related morbidities in HIV-infected people has frequently been found to be associated with nadir CD4 count and ART duration.
Cataracts are opacities of the intraocular lens, and the prevalence of lens opacities increases exponentially with age. They are a leading cause of blindness and visual impairment worldwide. Individuals with cataract have an increased mortality risk than those without, even after adjusting for known confounders. The human lens is considered an ideal tissue for studying macromolecular aging, as biochemical mechanisms in lens proteins may reflect aging processes elsewhere in the body. In the context of lens opacities and HIV, 2 possible scenarios exist. First, although the prevalence of HIV-related opportunistic ocular infections [such as cytomegalovirus (CMV) retinitis] has decreased, the introduction and scale-up of ART has led to immune recovery phenomena. This may manifest in the eye as "immune recovery uveitis" (IRU). It is characterized by ocular inflammation after ART initiation and can lead to cataract formation. Second, if premature aging does occur in HIV-infected individuals, an increased risk of ocular age-related conditions such as cataract might be expected. To date, there is minimal information about age-related eye conditions and the possibility of accelerated aging in HIV-infected patients, particularly within sub-Saharan Africa.
The Pentacam (Oculus, Wetzlar, Germany) is a 360-degree rotating noncontact camera that provides a rapid and precise 3 dimensional (3D) view of the lens, cornea, and anterior chamber. The Pentacam uses a blue light-emitting diode (wavelength 475 nm) to image the anterior eye segment, capturing 25 single-slit images in 2 seconds while rotating around the eye from 0 to 180 degrees. The instrument acquires data points that provide a representative image of the whole lens. The Pentacam contains integral software that can automatically quantify lens "density" by measuring the light-scattering intensity of the lens layers. This provides a form of objective lens opacity (cataract) grading. The objective of the study was to assess differences in lens density using the Pentacam in a cohort of HIV-infected individuals in comparison with an age-matched and a sex-matched HIV-seronegative group. Our study hypotheses were that (a) HIV-infected individuals will have a greater lens density compared with sex- and age-matched HIV-seronegative individuals and (b) low nadir CD4 count at ART initiation is associated with an increased risk of higher lens density. Our study was conducted in Cape Town, South Africa, with recruitment of cases and controls from the same communities to reduce the likelihood of differential risk exposure in line with the recommendation for careful study design when investigating premature aging in HIV.