SciCombinator

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Concept: HIV/AIDS

150

The objectives of this study were to determine if a video improved HIV/AIDS and HIV testing knowledge among a global sample of Internet users, to discern if this improvement was the same for English and Spanish speakers, and to ascertain if the video was efficacious for those with lower health literacy. A worldwide sample of English- or Spanish-speaking Internet users was solicited. Participants completed a 25-item questionnaire to assess their HIV/AIDS and HIV testing knowledge before and after watching the video. Mean scores on the questionnaire improved after watching the video for both English speakers (after: 19.6 versus before: 16.4; Δ = 3.2; 95% confidence interval [CI]: 2.8-3.5) and Spanish speakers (20.7 versus 17.3; Δ = 3.4; 95% CI: 3.0-3.8). There was no difference in improvement of scores between English and Spanish speakers (Δ = -0.24; 95% CI: -0.79 to 0.31), and this video was equally efficacious for those with lower and higher health literacy skills.

Concepts: HIV/AIDS, Better, Statistics, Improve, Sample size, Spanish language, South Africa, English language

101

The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome ‘snapshot’ reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as ‘Patient 0’ (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.

Concepts: HIV, AIDS, HIV/AIDS, Virus, Genome, United States, North America, Caribbean

35

Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated.

Concepts: Antiretroviral drug, HIV, AIDS, Protease inhibitor, Immune system, HIV/AIDS, Infectious disease, Acute HIV infection

30

Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state. We generated a stabilized, soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 Å. Its overall conformation is similar to SOSIP.664 and native Env trimers but includes a covalent linker between gp120 and gp41, an engineered 201-433 disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided design strategies resulted in multiple homogeneous cross-clade immunogens with the potential to advance HIV vaccine development.

Concepts: HIV, Immune system, HIV/AIDS, Structure, Discovery and development of CCR5 receptor antagonists, Gp41, HIV vaccine, Gp120

30

The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk.

Concepts: Antiretroviral drug, HIV, AIDS, HIV/AIDS, Viral load, Scientific method, Cohort study, Acute accent

29

The aim of the study was to examine the prevalence of HIV infection in patients presenting in primary care with glandular fever (GF)-like illness.

Concepts: HIV, HIV/AIDS, Infectious disease, Cytomegalovirus, Fever, Malaise, Infectious mononucleosis, Acute HIV infection

28

We reviewed recent literature on the cascade of HIV care from HIV testing to suppression of viral load, which has emerged as a critical focus as HIV treatment programs have scaled up.

Concepts: Antiretroviral drug, HIV, HIV/AIDS, Viral load, HIV test

28

Fourth-generation human immunodeficiency virus-1 (HIV-1) screening assays have improved sensitivity, but vary in performance characteristics. The purpose of this study was to evaluate four different fourth-generation HIV-1 assays. These assays included the AxSYM HIV Ag/Ab Combo (Abbott diagnostics, Delkenheim, Germany), ARCHITECT HIV Ag/Ab Combo (Abbott), Elecsys 2010 HIV Combi (Roche Diagnostics GmbH, Mannheim, Germany), and Elecsys HIV Combi PT (Roche). A total of 1,306 samples that included 1,225 clinical samples and 81 samples consisting of seroconversion panels, an HIV-1 p24 antigen sensitivity panel, and dilution series of HIV-1 lysates and HIV-1 antibodies were tested. All of the assays had sensitivities of 100% on clinical samples. The specificities of the AxSYM, ARCHITECT, Elecsys 2010 HIV Combi, and Elecsys HIV Combi PT were 99.6, 99.6, 99.0, and 99.5%, respectively. Of the 81 samples with different levels of HIV antigen or antibody and/or subtypes, Elecsys HIV Combi PT and ARCHITECT HIV Ag/Ab Combo showed better analytical sensitivities than the other two assays. In summary, the performance characteristics of AxSYM, ARCHITECT, and Elecsys HIV Combi PT were comparable and satisfactory for clinical samples. ARCHITECT HIV Ag/Ab Combo and Elecsys HIV Combi PT have the higher analytical sensitivities, and would be preferable for reducing the window period. J. Med. Virol. 84:1884-1888, 2012. © 2012 Wiley Periodicals, Inc.

Concepts: HIV, Immune system, Antibody, HIV/AIDS, Subtypes of HIV, ELISA, Serology, Roche Diagnostics

28

HIV controllers are a valuable source for the identification of HIV-neutralizing antibodies, as chronic infection over decades allows extensive affinity maturation of antibodies for improved antigen recognition. We analyzed a small cohort of elite controllers (ECs) for HIV neutralizing antibodies using a panel of standardized HIV-1 pseudovirions on TZM-bl cells. An HIV-1 Env-tailored phage display library was generated to select epitopes targeted by neutralizing antibodies in the EC26 plasma sample showing the broadest neutralizing activity. Selected Env fragments were mostly allocated to the membrane proximal external region (MPER) of gp41. After preabsorbing the EC26 plasma with the selected phage EC26-2A4, we achieved 50% depletion of its neutralizing activity. Furthermore, antibodies affinity-purified with the EC26-2A4 epitope from EC26 plasma showed neutralizing activity, proving that the selected phage indeed contains an epitope targeted by neutralizing plasma antibodies. Epitope fine mapping of the purified plasma antibodies on peptide arrays identified a new epitope overlapping, but clearly distinct, from the prominent 2F5 epitope. Of note, the purified antibodies did not show autoreactivity with cardiolipin, whereas low reactivity with phosphatidylserine comparable to mAb 2F5 was observed. Thus, this new epitope represents a promising candidate for further analysis in view of HIV vaccine development.

Concepts: HIV, Immune system, Antibody, HIV/AIDS, Discovery and development of CCR5 receptor antagonists, Antigen, Epitope, Phage display

28

We quantified vaginal lactobacilli and determined their relationship with genital HIV-1 shedding and found a significant negative association between reduced quantity of lactobacilli and cervical HIV-1 viral load (r(2) = - 0.8900, P < 0.01), which may have implications of increased chances of sexual transmission of HIV-1 and genital infections.

Concepts: HIV, HIV/AIDS, Viral load, Sexual intercourse, Bacteria, Female reproductive system, Cytomegalovirus, Clitoris