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The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies (1-5). However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal [SIV.sub.MAC251] infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7,10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies., The viral reservoir in memory [CD4.sup.+] T cells in HIV-1-infected individuals cannot be eliminated by current antiretroviral drugs or HIV-1-specific immune responses (1-5). This archive of replication-competent virus is the [...]

Purpose: Few studies have examined telehealth use among rural Medicaid beneficiaries. This study produced a descriptive overview of telehealth use in 2011, including the prevalence of telehealth use among rural and urban Medicaid beneficiaries, characteristics of telehealth users, types of telehealth services provided, and diagnoses associated with telehealth use. Methods: Using data from the 2011 Medicaid Analytic eXtract (MAX), we conducted bivariate analyses to test the associations between rurality and prevalence and patterns of telehealth use among Medicaid beneficiaries. Findings: Rural Medicaid beneficiaries were more likely to use telehealth services than their urban counterparts, but absolute rates of telehealth use were low—0.26% of rural nondual Medicaid beneficiaries used telehealth in 2011. Psychotropic medication management was the most prevalent use of telehealth for both rural and urban Medicaid beneficiaries, but the proportion of users who accessed nonbehavioral health services through telehealth was significantly greater as rurality increased. Regardless of telehealth users' residence, mood disorders were the most common reason for obtaining telehealth services. As rurality increased, significantly higher proportions of telehealth users received services to address attention‐deficit/hyperactivity disorder (ADHD) and other behavioral health problems usually diagnosed in childhood. Conclusions: These findings provide a baseline for further policy‐relevant investigations including examinations of changes in telehealth use rates in Medicaid since 2011. Reimbursement policies and unique rural service needs may account for the observed differences in rural‐urban Medicaid telehealth use rates. [ABSTRACT FROM AUTHOR]

Despite the widespread use of replication-incompetent recombinant adenovirus (Ad) vectors as candidate vaccine platforms, the mechanism by which these vectors elicit CD8+ T cell responses remains poorly understood. Our data demonstrate that induction and maintenance of CD8+ T cell responses by Ad vector immunization is longitudinally dependent on CD4+ T cell help for a prolonged period. Depletion of CD4+ T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8+ T cells, decreased T-bet and eomesodermin expression, impaired KLRG1+ effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L. Moreover, these CD8+ T cells failed to protect against a lethal recombinant Listeria monocytogenes challenge. Depletion of CD4+ T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8+ T cells. These data demonstrate a prolonged temporal requirement for CD4+ T cell help for vaccine-elicited CD8+ T cell responses in mice. These findings have important implications in the design of vaccines aimed at eliciting CD8+ T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4+ T cell immune deficiencies. [ABSTRACT FROM AUTHOR]