Material

No abstract

In contrast to human immunodeficiency virus (HIV)-infected humans, natural hosts for simian immunodeficiency virus (SIV) very rarely progress to acquired immunodeficiency syndrome (AIDS).While the mechanisms underlying this disease resistance are still poorly understood, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To investigate the immunologic mechanisms underlying the absence of AIDS in SIV-infected sooty mangabeys (SMs), a natural host species, we performed a detailed analysis of the SIV-specific cellular immune responses in 110 SIV-infected SMs. We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIVinfected humans, both in terms of cytokine production (ie, IFN-␥, TNF-␣, and IL-2) and degranulation (ie, CD107a expression). Of importance, SIV-specific Tcell responses were similarly low when either SIVmac239-derived peptides or autologous SIVsmm peptides were used as stimuli. No correlation was found between SIV-specific T-cell responses and either viral load or CD4 ؉ T-cell count, or between these responses and markers of T-cell activation and proliferation. These findings indicate that the absence of AIDS in naturally SIV-infected sooty mangabeys is independent of a strong cellular immune response to the virus. IntroductionThe acquired immunodeficiency syndrome (AIDS) pandemic originated from zoonotic transmission of simian immunodeficiency viruses (SIVs) from infected African monkey species to humans. 1 Of the natural SIV hosts, sooty mangabeys (Cercocebus atys, SMs) are of interest for 2 main reasons. First, SIVsmm, the virus infecting SMs, is the origin of the human immunodeficiency virus 2 (HIV-2) epidemic in humans. 1-3 Second, SIVsmm is the source of the prototype SIVmac strains (ie, SIVmac239, SIVmac251) that induce an AIDS-like disease in the rhesus macaque (RM), a nonnatural host for SIV, and consequently are widely used for studies of AIDS pathogenesis and vaccines. 2,4-6 SIVsmm and HIV-1/2 share many features in terms of life cycle and molecular structure, and the extent of virus replication is similarly high in naturally SIV-infected SMs and HIV-infected humans. 7-9 However, the outcome of these infections is strikingly different. The vast majority of HIV-infected humans, unless treated chronically with antiretroviral therapy (ART), will develop progressive CD4 ϩ T-cell depletion and eventually succumb to AIDS. In contrast, the vast majority of naturally SIV-infected SMs maintain normal CD4 ϩ T-cell counts and live an apparently normal lifespan in captivity, [7][8][9] with only one report of classic AIDS to date. 10 It is important to note that the disease resistance of naturally SIV-infected SMs that show high levels of SIV viremia is substantially different from that of a rare subset of HIV-infected individuals defined as long-term nonprogressors, in whom viral replication is usually very lo...

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

IMPORTANCE Retinal telescreening for evaluation of diabetic retinopathy (DR) in the primary care setting may be useful in reaching rural and underserved patients.OBJECTIVES To evaluate telemedicine retinal screenings for patients with type 1 or 2 diabetes and identify factors for ophthalmology referral in the North Carolina Diabetic Retinopathy Telemedicine Network. DESIGN, SETTING, AND PARTICIPANTSA preimplementation and postimplementation evaluation was conducted from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving rural and underserved populations in North Carolina among 1787 adult patients with type 1 or 2 diabetes who received primary care at the clinics and obtained retinal telescreening to determine the presence and severity of DR. A total of 1661 patients with complete data were included in the statistical analysis.INTERVENTION Nonmydriatic fundus photography with remote interpretation by an expert. MAIN OUTCOMES AND MEASURESNumber of patients recruited, level of detected DR, change in rates of screening, rate of ophthalmology referral, percentage of completed referrals, and patient characteristics associated with varying levels of DR. RESULTSOf the 1661 patients (1041 women and 620 men; mean [SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients (11.0%) had DR without a need for an ophthalmology referral, and 155 patients (9.3%) had DR with a need for an ophthalmology referral. The mean rate of screening for DR before implementation of the program was 25.6% (1512 of 5905), which increased to 40.4% (1884 of 4664) after implementation. A total of 93 referred patients (60.0%) completed an ophthalmology referral visit within the study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an ophthalmology referral compared with white and/or younger patients. Patients with higher hemoglobin A 1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53-2.02 per decade) had greater odds of DR requiring an ophthalmology referral. History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95% CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral. CONCLUSIONS AND RELEVANCEWhen implemented in the primary care setting, retinal telescreening increased the rate of evaluation for DR for patients in rural and underserved settings. This strategy may also increase access to care for minorities and patients with DR requiring treatment.