Search

Pneumocystis pneumonia (PCP) has historically been one of the leading causes of disease among persons with AIDS. The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. In the adult population, the incidence of PCP has significantly decreased, but it remains among the most common AIDS-defining infections. Similar declines have been documented in the pediatric population. In much of the developing world, PCP remains a significant health problem, although its incidence among adults in sub-Saharan Africa has been debated. This review discusses the epidemiology of PCP during the current era of the AIDS epidemic. Although fewer cases of PCP occur in industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and the tremendous number of AIDS cases in developing countries make this disease of continued public health importance.

The availability of reliable laboratory methods for determining recent HIV infection is vital for accurate estimation of population-based incidence. The mean duration of recent infection (MDRI) and false recent rate (FRR) are critical parameters for HIV incidence assays, as they impact HIV incidence estimates and provide a measure of assay performance. The HIV-1 Multiplex assay is an in-house developed, magnetic bead-based assay that measures virus-specific antibody levels and avidity to multiple analytes. To ensure quality control and to facilitate transfer of the assay to external laboratories or testing facilities, the in-house assay has been adapted and produced in kit form. Here, we describe the performance characteristics of the multiplex kit and demonstrate the stability of the kit components over a one-year period. Two statistical methods were employed to estimate the MDRI of the individual analytes and five different algorithms, combining multiple analyte values. The MDRI estimates for the individual analytes and five algorithms were all between 200 and 300 days post-seroconversion, with no notable difference between the two statistical approaches. All five algorithms exhibited a 0% FRR with specimens from long-term, subtype B HIV-1-infected individuals. The assay parameters described in this study provide the necessary tools to implement the HIV-1 multiplex assay and improves the utility of the assay for field use. [ABSTRACT FROM AUTHOR]

HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. [ABSTRACT FROM AUTHOR]

Objectives: Accurate methods of estimating HIV-1 incidence are critical for monitoring the status of the epidemic and the impact of prevention strategies. Although several laboratory-based tests have been developed strictly for this purpose, several limitations exist and improved methods or technologies are needed. We sought to further optimize a previously described bead-based, HIV-1-specific multiplex assay with the capability of measuring multiple immune responses for determining recent infection. Methods: We refined the customized HIV-1 Bio-Plex assay by determining cutoffs and mean durations of recency (MDR), based on the reactivity to longitudinal seroconversion specimens (n = 1347) from 311 ART-naïve, HIV-1-infected subjects. False-recent rates (FRRs) were calculated for various long-term cohorts, including AIDS patients, individuals on ART, and subtype C specimens. Incidence was estimated for each individual assay analyte from a simulated population with a known incidence of 1%. For improved incidence estimates, multi-analyte algorithms based on combinations of 3 to 6 analytes were evaluated and compared to the performance of each individual analyte. Results: The MDR for the six analytes varied from 164.2 to 279.4 days, while the multi-analyte algorithm MDRs were less variable with a minimum and maximum value of 228.4 and 277.9 days, respectively. The FRRs for the 7 multi-analyte algorithms evaluated in this study varied from 0.3% to 3.1%, in a population of ART-naïve, long-term individuals. All algorithms yielded improved incidence estimates as compared to the individual analytes, predicting an incidence of 0.95% to 1.02%. Conclusions: The HIV-specific multiplex assay described here measures several distinct immune responses in a single assay, allowing for the consideration of multi-analyte algorithms for improved HIV incidence estimates. [ABSTRACT FROM AUTHOR]

Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000–2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria. [ABSTRACT FROM AUTHOR]