Diagnostic point-of-care (POC) testing is intended to minimize the time to obtain a test result, thereby allowing clinicians and patients to make an expeditious clinical decision. As POC tests expand into resource-limited settings (RLS), the benefits must outweigh the costs. To optimize POC testing in RLS, diagnostic POC tests need rigorous evaluations focused on relevant clinical outcomes and operational costs, which differ from evaluations of conventional diagnostic tests. Here, we reviewed published studies on POC testing in RLS, and found no clearly defined metric for the clinical utility of POC testing. Therefore, we propose a framework for evaluating POC tests, and suggest and define the term “test efficacy” to describe a diagnostic test’s capacity to support a clinical decision within its operational context. We also proposed revised criteria for an ideal diagnostic POC test in resource-limited settings. Through systematic evaluations, comparisons between centralized diagnostic testing and novel POC technologies can be more formalized, and health officials can better determine which POC technologies represent valuable additions to their clinical programs.

In all but the lowest-risk populations, routine, voluntary screening for HIV once every three to five years is justified on both clinical and cost-effectiveness grounds. One-time screening in the general population may also be cost-effective.

Treatment of HIV infection with a combination of three antiretroviral drugs is a cost-effective use of resources.

At least 3.0 million years of life have been saved in the United States as a direct result of care of patients with AIDS, highlighting the significant advances made in HIV disease treatment.

Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.

Rationale: To improve the effectiveness of tuberculosis (TB) control programs in the United States by identifying cost-effective priorities for screening for latent tuberculosis infection (LTBI). Objectives: To estimate the cost-effectiveness of LTBI screening using the tuberculin skin test (TST) and interferon-g release assays (IGRAs). Methods: A Markov model of screening for LTBI with TST and IGRA in risk-groups considered in current LTBI screening guidelines. Measurements and Main Results: In all risk-groups, TST and IGRA screening resulted in increased mean life expectancy, ranging from 0.03-0.24 life-months per person screened. IGRA screening resulted in greater life expectancy gains than TST. Screening always cost more than not screening, but IGRA was cost-saving compared with TST in some groups. Four patterns of cost-effectiveness emerged, related to four risk categories. (1) Individuals at highest risk of TB reactivation (close contacts and those infected with HIV): the incremental cost-effectiveness ratio (ICER) of IGRA compared with TST was less than $100,000 per quality-adjusted life year (QALY) gained.(2) The foreign-born: IGRA was cost-saving compared with TST and cost-effective compared with no screening (ICER ,$100,000 per QALY gained). (3) Vulnerable populations (e.g., homeless, drug user, or former prisoner): the ICER of TST screening was approximately $100,000-$150,000 per QALY gained, but IGRA was not cost-effective. (4) Medical comorbidities (e.g., diabetes): the ICER of screening with TST or IGRA was greater than $100,000 per QALY. Conclusions: LTBI screening guidelines could make progress toward TB elimination by prioritizing screening for close contacts, those infected with HIV, and the foreign-born regardless of time living in the United States. For these groups, IGRA screening was more costeffective than TST screening.Keywords: latent tuberculosis; cost-effectiveness; tuberculin skin test; interferon-g release assay Reactivation of latent tuberculosis infection (LTBI) accounts for approximately 70% of cases of active tuberculosis (TB) in the United States (1, 2). Screening and treatment for LTBI is therefore a cornerstone of the strategy for the elimination of TB disease in the United States (3, 4). Previous studies have examined priorities for LTBI screening and treatment, and several have found that isoniazid (INH) therapy for low-risk tuberculin reactors is cost-effective, and even cost-saving in some populations (5-8). These studies, however, used estimates of the prevalence of LTBI and rates of reactivation TB observed in the 1950s and 1960s, and may not reflect current epidemiologic trends (9-11). Furthermore, given the development of interferon-g release assays (IGRA) as a screening test for LTBI, it is important to expand the investigation to compare the effectiveness and cost-effectiveness of both tuberculin skin test (TST) and IGRA screening (4). Although prior studies have investigated the cost-effectiveness of IGRA, they focused on select risk-groups, and did not prioritize s...

Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8 ؉ T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.

Screening HIV-positive homosexual and bisexual men for ASIL and anal SCC with anal Pap tests offers quality-adjusted life expectancy benefits at a cost comparable with other accepted clinical preventive interventions.