Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States.

Background: Human immunodeficiency virus type 1 (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood. We used ultradeep sequencing (UDS) to estimate the frequency of DI in a primary infection cohort of predominantly men who have sex with men (MSM).

Methods:  HIV-1 genomes from longitudinal blood samples of recently infected, therapy-naive participants were interrogated with UDS.

Dynamics of viral evolution and neutralizing antibody response after HIV-1 superinfection.

Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions.

HIV-1 clade B pol evolution following primary infection.

Objective: Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals.

Design: Longitudinal cohort study of individuals enrolled during primary infection.

Methods: Eligible individuals were antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection.

Using ultradeep pyrosequencing to study HIV-1 coreceptor usage in primary and dual infection.

HIV-1 dual infection (DI) and CXCR4 (X4) coreceptor usage are associated with accelerated disease progression but frequency and dynamics of coreceptor usage during DI is unknown. Ultradeep sequencing was used to interrogate for DI and infer coreceptor usage in longitudinal blood samples of 102 subjects. At baseline, X4 usage was high (23 subjects harbored X4 variants) and was not associated with infection duration or DI.

Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men.

Objective: To investigate the susceptibilities to and consequences of HIV-1 dual infection.

Design: We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B and monoinfected controls who were matched by ongoing HIV risk factor.

Methods: The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test).

Detection of minority resistance during early HIV-1 infection: natural variation and spurious detection rather than transmission and evolution of multiple viral variants.

Reports of a high frequency of the transmission of minority viral populations with drug-resistant mutations (DRM) are inconsistent with evidence that HIV-1 infections usually arise from mono- or oligoclonal transmission. We performed ultradeep sequencing (UDS) of partial HIV-1 gag, pol, and env genes from 32 recently infected individuals. We then evaluated overall and per-site diversity levels, selective pressure, sequence reproducibility, and presence of DRM and accessory mutations (AM).

Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure.

Background: Most of our knowledge about how antiretrovirals and host immune responses influence the HIV-1 protease gene is derived from studies of subtype B virus. We investigated the effect of protease resistance-associated mutations (PRAMs) and population-based HLA haplotype frequencies on polymorphisms found in CRF01_AE pro.

Methods: We used all CRF01_AE protease sequences retrieved from the LANL database and obtained regional HLA frequencies from the dbMHC database.

The efficiency of single genome amplification and sequencing is improved by quantitation and use of a bioinformatics tool.

Typically, population-based sequencing of HIV does not detect minority variants present at levels below 20-30%. Single genome amplification (SGA) and sequencing improves detection, but it requires many PCRs to find the optimal terminal dilution to use. A novel method for guiding the selection of a terminal dilution was developed and compared to standard methods.

A public health model for the molecular surveillance of HIV transmission in San Diego, California.

Background: Current public health efforts often use molecular technologies to identify and contain communicable disease networks, but not for HIV. Here, we investigate how molecular epidemiology can be used to identify highly related HIV networks within a population and how voluntary contact tracing of sexual partners can be used to selectively target these networks.

Methods: We evaluated the use of HIV-1 pol sequences obtained from participants of a community-recruited cohort (n = 268) and a primary infection research cohort (n = 369) to define highly related transmission clusters and the use of contact tracing to link other individuals (n = 36) within these clusters.

Herpes simplex virus type 2 acquisition during recent HIV infection does not influence plasma HIV levels.

We assessed the effect of herpes simplex virus type 2 (HSV-2) acquisition on the plasma HIV RNA and CD4 cell levels among individuals with primary HIV infection using a retrospective cohort analysis. We studied 119 adult, antiretroviral-naive, recently HIV-infected men with a negative HSV-2-specific enzyme immunoassay (EIA) result at enrollment. HSV-2 acquisition was determined by seroconversion on HSV-2 EIA, confirmed by Western blot analysis.

Sodium channel auxiliary subunits.

Voltage-gated ion channels are well known for their functional roles in excitable tissues. Excitable tissues rely on voltage-gated ion channels and their auxiliary subunits to achieve concerted electrical activity in living cells. Auxiliary subunits are also known to provide functional diversity towards the transport and biogenesis properties of the principal subunits.

Calcium channel auxiliary subunits.

Many channels and carriers associate with auxiliary subunits which modify their activities and facilitate biogenesis. Advances in genome sequencing as well as biochemical, molecular genetic, and physiological experimentation have allowed for the discovery of many transport auxiliary subunits. Recent interests in the pharmacology of the calcium auxiliary subunits prompted a large amount of effort in deciphering their specific role in the conductance of calcium ions.