HIV This Week

Grabar S, Selinger-Leneman H, Abgrall S, Pialoux G, Weiss L, Costagliola D. Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS. 2009;23(9):1163-9.

Grabar and colleagues set out to estimate the prevalence and characteristics of long-term nonprogressor and HIV controller patients in a very large French cohort of HIV 1-infected patients. In the French Hospital Database on HIV [FHDH, Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4], they selected patients who had been seen in 2005, who had been infected for more than 8 years, who were treatment-naive, and who remained asymptomatic. Patients with these characteristics then categorized as follows: long-term nonprogressor (> or =8 years of HIV infection and CD4 cell nadir > or =500/microl), elite long-term nonprogressor (> or =8 years of HIV infection, CD4 cell nadir > or =600/microl, and a positive CD4 slope), HIV controllers (>10 years of HIV infection with 90% of plasma viral load values < or =500 copies/ml), and elite controllers (same as HIV controllers, but with last plasma viral load value < or =50 copies/ml in 2005). Among the 46 880 HIV-1-infected patients followed in 2005 in the French Hospital Database on HIV, 0.4% (N = 202) were long-term nonprogressor, 0.05% (N = 25) were elite long-term nonprogressor, 0.22% (N = 101) were HIV controllers, and 0.15% (N = 69) were elite controllers. Ten elite long-term nonprogressor patients (40% of 25) were also HIV controllers, eight (32%) were elite controllers, and 60% had detectable plasma viral load (>50 copies/ml). Among the elite controllers, 32 (46%) were long-term nonprogressor, eight (12%) were elite long-term nonprogressor, and one-quarter had a last CD4 cell count less than 500/microl. Long-term nonprogressor, elite LTNP, HIV controller, and elite controller patients are rare phenotypes. Elite long-term nonprogressor patients are less frequent than HIV controllers. There is little overlap among the four subgroups of patients.

Editors’ note: With the advent of viral load assays in clinical care, new groups of patients with slow disease progression joined the patients known as long-term nonprogressors. Defined by virologic parameters, they are called the HIV controllers, some of whom are elite controllers. Although the definitions of these various groups vary in the literature and there is some overlap, they are of intense interest because the mechanisms by which they have some natural protection against HIV may provide insights for the development of preventive and therapeutic vaccines. Both viral factors and host genetic factors, such as HLA-B27 and HLA-B57, may play a role. This study of more than 110,000 patients confirms the very low prevalence (less than 0.5%) of these valuable patients. Some are viraemic with high CD4 counts while others control viraemia but have CD4 depletion and yet others appear to have both viral control and stable CD4 cell counts.

Lassen KG, Lobritz MA, Bailey JR, Johnston S, Nguyen S, Lee B, Chou T, Siliciano RF, Markowitz M, Arts EJ.  Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. PLoS Pathog. 2009;5(4):e1000377.

Elite suppressors are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy.  Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses elite suppressors plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, elite supressors envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. Elite suppressors envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, elite suppressors env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from elite suppressors or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in elite suppressors individuals.

Editors’ note: This study is the first to provide direct evidence that the envelope glycoprotein, the coat protein of HIV, in elite suppressors is less efficient in supporting HIV entry into host cells that that of HIV found in people with disease progression. In acute infection, there are HIV variants with a wide range of efficiencies, suggesting that elite suppressors may be selecting relatively lower fitness env variants right at the start. How they would do this remains a mystery, as no data exist on the natural history of acute infection in elite suppressors.