Background There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized. Methods We used population-level longitudinal data from province-wide registries including plasma viral load, CD4 count, drug resistance, HAART use, HIV diagnoses, AIDS incidence, and HIV-related mortality. We fitted two Poisson regression models over the study period, to relate estimated HIV incidence and the number of individuals on HAART and the percentage of virologically suppressed individuals. Results HAART coverage, median pre-HAART CD4 count, and HAART adherence increased over time and were associated with increasing virological suppression and decreasing drug resistance. AIDS incidence decreased from 6.9 to 1.4 per 100,000 population (80% decrease, p = 0.0330) and HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003). Finally, our models suggested that for each increase of 100 individuals on HAART, the estimated HIV incidence decreased 1.2% and for every 1% increase in the number of individuals suppressed on HAART, the estimated HIV incidence also decreased by 1%. Conclusions Our results show that HAART expansion between 1996 and 2012 in BC was associated with a sustained and profound population-level decrease in morbidity, mortality and HIV transmission. Our findings support the long-term effectiveness and sustainability of HIV treatment as prevention within an adequately resourced environment with no financial barriers to diagnosis, medical care or antiretroviral drugs. The 2013 Consolidated World Health Organization Antiretroviral Therapy Guidelines offer a unique opportunity to further evaluate TasP in other settings, particularly within generalized epidemics, and resource-limited setting, as advocated by UNAIDS.

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Expansion of HAART Coverage Is Associated with Sustained Decreases in HIV/AIDS Morbidity, Mortality and HIV Transmission: The “HIV Treatment as Prevention” Experience in a Canadian Setting

Introduction In the history of sexually transmitted infection (STI) control, as with other communicable diseases, the pendulum swings between vertical disease-specific and broader horizontal approaches, from a narrow focus on pathogens and their treatment to the wider needs of populations who host and transmit them Since the emergence of HIV in the 1980s, STI control efforts have increasingly been defined in relation to HIV programme priorities (1) Although HIV is itself an STI, efforts to prevent its transmission are largely managed through programmes that are funded, implemented and evaluated independently of other STI control efforts Such a fractured paradigm has had unfortunate consequences Too often, neglected STI programmes--the foundation upon which HIV prevention efforts were built--collapse due to reduced funding As a result, STI clinics and services are understaffed, understocked or disappearing altogether; pregnant women may be offered HIV tests but are no longer screened for syphilis; and STI reporting, an important marker of sexual transmission trends, has largely collapsed (2,3) In other areas of communicable disease control, the pendulum is moving in a different direction towards strategies that aim for broad public health benefit while pursuing disease-specific control objectives Examples include attention to general lung health within the Stop TB partnership and integrated vector management in malaria efforts The rationale is that sustainable disease control requires coordinated efforts to address common conditions that may facilitate transmission or impede access to prevention, case detection, diagnosis and treatment (4,5) This paper describes a unified paradigm of STI control where HIV is an important focus The approach is analytical and programme-oriented, with attention to public health outcomes and means We start by reviewing definitions and outlining basic components of STI control, and then examine empirical evidence of the feasibility and benefits of STI control under different conditions We also consider what happens to HIV under different scenarios and look at the overlap and potential synergies between HIV prevention and STI control efforts Defining STI control STI control is a public health outcome, measured as reduced incidence and prevalence, achieved by implementing strategies composed of multiple synergistic interventions In the literature, the term "STI control" is frequently used interchangeably with "STI treatment", yet these are quite different things (6,7) Control of any communicable disease is a public health outcome, measured as reduced prevalence (total infections) or incidence (new infections) in a population Treatment is a biomedical intervention that, unless part of a broader control strategy, usually does not result in lower transmission rates or disease burden STI control can be measured in absolute or relative terms, for example, as elimination of chancroid or 50% reduction of the prevalence of gonorrhoea Monitoring trends of common curable STIs, etiologically or syndromically, can provide evidence of changing incidence Where STI surveillance is supported and functioning (often it is not), these data also reflect general sexual transmission trends and can be used to assess the adequacy of overall STI/HIV prevention efforts (8) Since HIV shares many aspects with other STIs--including modes of transmission, behavioural and other cofactors and potential control measures--HIV prevention can logically be situated within the larger, encompassing domain of STI control Back to basics A comprehensive STI control strategy includes targeted community-based interventions, promotion and provision of the means of prevention and effective clinical services within an enabling environment, as well as reliable data to guide the response The science and methods of STI control build on several centuries' experience backed by evidence of progressively declining incidence and prevalence, particularly in developed countries? …

Control of Sexually Transmitted Infections and Prevention of HIV Transmission: Mending a Fractured paradigm/Lutte Contre Les Infections Sexuellement Tranmissibles et Prevention De la Transmission Du VIH: Reconstitution D'un Dispositif deteriore/Control De Las Infecciones De Transmision Sexual Y Prevencion De la Transmision del VIH: Reparar la Fractura

Introduction Strategies to increase uptake of next-generation biomedical prevention technologies (e.g., long-acting injectable pre-exposure prophylaxis (PrEP)) can benefit from understanding associations between religion, faith, and spirituality (RFS) and current primary HIV prevention activities (e.g., condoms and oral PrEP) along with the mechanisms which underlie these associations. Methods We searched PubMed, Embase, Academic Search Premier, Web of Science, and Sociological Abstracts for empirical articles that investigated and quantified relationships between RFS and primary HIV prevention activities outlined by the United States (U.S.) Department of Health and Human Services: condom use, HIV and STI testing, number of sexual partners, injection drug use treatment, medical male circumcision, and PrEP. We included articles in English language published between 2000 and 2020. We coded and analyzed studies based on a conceptual model. We then developed summary tables to describe the relation between RFS variables and the HIV prevention activities and any underlying mechanisms. We used CiteNetExplorer to analyze citation patterns. Results We identified 2881 unique manuscripts and reviewed 29. The earliest eligible study was published in 2001, 41% were from Africa and 48% were from the U.S. RFS measures included attendance at religious services or interventions in religious settings; religious and/or spirituality scales, and measures that represent the influence of religion on behaviors. Twelve studies included multiple RFS measures. Twenty-one studies examined RFS in association with condom use, ten with HIV testing, nine with number of sexual partners, and one with PrEP. Fourteen (48%) documented a positive or protective association between all RFS factors examined and one or more HIV prevention activities. Among studies reporting a positive association, beliefs and values related to sexuality was the most frequently observed mechanism. Among studies reporting negative associations, behavioral norms, social influence, and beliefs and values related to sexuality were observed equally. Studies infrequently cited each other. Conclusion More than half of the studies in this review reported a positive/protective association between RFS and HIV prevention activities, with condom use being the most frequently studied, and all having some protective association with HIV testing behaviors. Beliefs and values related to sexuality are possible mechanisms that could underpin RFS-related HIV prevention interventions. More studies are needed on PrEP and spirituality/subjective religiosity.

/pdf/religion-faith-and-spirituality-influences-on-hiv-prevention-2p8151ywui.pdf

Religion, faith, and spirituality influences on HIV prevention activities: A scoping review.

Background: Despite renewed focus on biomedical prevention strategies since the publication of several clinical trials highlighting the efficacy of pre-exposure prophylaxis (PrEP), knowledge of postexposure prophylaxis (PEP) and PrEP continues to remain scarce among women, especially among African American women who are disproportionally affected by HIV. In an effort to address this barrier and encourage uptake of PEP and PrEP, an electronic health (eHealth) video was created using an entertainment-education format. Objective: The study aimed to explore the feasibility, acceptability, and preference of an avatar-led, eHealth video, PEP and PrEP for Women, to increase awareness and knowledge of PEP and PrEP for HIV in a sample of African American women. Methods: A cross-sectional, Web-based study was conducted with 116 African American women aged 18 to 61 years to measure participants’ perceived acceptability of the video on a 5-point scale: poor, fair, good, very good, and excellent. Backward stepwise regression was used to the find the outcome variable of a higher rating of the PEP and PrEP for Women video. Thematic analysis was conducted to explore the reasons for recommending the video to others after watching the eHealth video. Results: Overall, 89% of the participants rated the video as good or higher. A higher rating of the educational video was significantly predicted by: no current use of drugs/alcohol (beta=−.814; P=.004), not having unprotected sex in the last 3 months (beta=−.488; P=.03), higher income (beta=.149; P=.03), lower level of education (beta=−.267; P=.005), and lower exposure to sexual assault since the age of 18 years (beta=−.313; P=.004). After watching the eHealth video, reasons for recommending the video included the video being educational, entertaining, and suitable for women. Conclusions: Utilization of an avatar-led eHealth video fostered education about PEP and PrEP among African American women who have experienced insufficient outreach for biomedical HIV strategies. This approach can be leveraged to increase awareness and usage among African American women.

/pdf/utilization-of-an-animated-electronic-health-video-to-2a01d9xblv.pdf

Utilization of an Animated Electronic Health Video to Increase Knowledge of Post- and Pre-Exposure Prophylaxis for HIV Among African American Women: Nationwide Cross-Sectional Survey.

Background Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. Methods In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 mu g total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 mu g total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 10(8) pfu HIV-MVA at weeks 30 and 46. Results 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-gamma ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-gamma ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-gamma/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. Conclusions A simplified intradermal vaccination regimen with 2 injections of a total of 600 mu g with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 mu g with separated plasmid pools after boosting twice with HIV-MVA.

/pdf/priming-with-a-simplified-intradermal-hiv-1-dna-vaccine-3zcakggbn4.pdf

Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.

/pdf/translation-of-biomedical-prevention-strategies-for-hiv-2vcdzftmhn.pdf

Translation of biomedical prevention strategies for HIV: prospects and pitfalls.

Abstract PCR-based diagnostics generally require nucleic acid extraction from patient specimens prior to amplification. As highlighted early in the COVID-19 pandemic, extraction steps may be difficult to scale during times of massive demand and limited reagent supply. Forgoing an extraction step, we previously reported that the N1 primer/probe-set of the widespread CDC COVID-19 assay maintains high categorical sensitivity (95%) and specificity (100%) with direct inoculation of viral transport media (VTM) into qRT-PCR reactions. In contrast, the N2 set demonstrated a prominent C t delay and low sensitivity (33%) without extraction. In the current study, we have improved the performance of this modified CDC assay (in particular the N2 set) by incorporating N1/N2/RNase P multiplexing and dissecting the effects of annealing temperature, VTM interference, and inoculum volume. The latter two factors exerted a more prominent effect on the performance of N2 than N1, although these effects were largely overcome through elevated annealing temperature. This unextracted/multiplex protocol was evaluated with 41 SARS-CoV-2 positive and 43 negative clinical samples, demonstrating a categorical sensitivity of 92.7% and specificity of 100% versus the unmodified CDC methodology. Overall, this work offers a generalizable strategy to maximize testing capabilities for COVID-19 or other emerging pathogens when resources are constrained. 

/pdf/direct-pcr-with-the-cdc-2019-sars-cov-2-assay-optimization-3bd4bxdd.pdf

Direct PCR with the CDC 2019 SARS-CoV-2 assay: optimization for limited-resource settings

HIV develops single nucleotide polymorphisms (SNPs), some of which lead to drug resistance mutations (DRMs) that prevent therapeutic viral suppression. Genomic sequencing enables healthcare professionals to select effective combination antiretroviral therapy (ART) to achieve and maintain viral suppression. However, sequencing technologies, which are resource-intensive, are limited in their availability. This report describes the first step toward a highly specific ligation-based SNP discrimination method with endpoint PCR detection, which is more suitable for resource-limited clinics. The approach is based on magnetic bead processing to maximize reaction product transfer and minimize the carryover of incompatible buffer for three consecutive enzymatic reactions─reverse transcription (RT), oligonucleotide ligation assay (OLA), and PCR. The method improved PCR detection following RT → OLA by 8.06 cycles (∼250-fold) compared to direct pipette processing and detected between 103 and 104 RNA copies per reaction. In studies with synthesized nucleic acids based on the well-studied HIV mutation, K103N, the assay successfully differentiated between wild-type and mutant for RNA targets with high specificity. With further development, this design provides a pathway for SNP detection with more accessible PCR instrumentation and is a step toward a self-contained processing approach that incorporates the SNP specificity of the ligation reaction for more effective clinical management of DRMs in resource-constrained settings.

Magnetic Bead Processing Enables Sensitive Ligation-Based Detection of HIV Drug Resistance Mutations.

ADVERTISEMENT RETURN TO ARTICLES ASAPPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Low-Resource Nucleic Acid Extraction Method Enabled by High-Gradient Magnetic Separation”Stephanie I. PearlmanStephanie I. PearlmanMore by Stephanie I. Pearlmanhttps://orcid.org/0000-0003-3909-1088, Mindy LeelawongMindy LeelawongMore by Mindy Leelawong, Kelly A. RichardsonKelly A. RichardsonMore by Kelly A. Richardson, Nicholas M. AdamsNicholas M. AdamsMore by Nicholas M. Adams, Patricia K. RussPatricia K. RussMore by Patricia K. Russ, Megan E. PaskMegan E. PaskMore by Megan E. Pask, Anna E. WolfeAnna E. WolfeMore by Anna E. Wolfe, Cassandra WesselyCassandra WesselyMore by Cassandra Wessely, and Frederick R. Haselton*Frederick R. HaseltonMore by Frederick R. Haseltonhttps://orcid.org/0000-0003-4282-5222Cite this: ACS Appl. Mater. Interfaces 2023, XXXX, XXX, XXX-XXXPublication Date (Web):December 21, 2023Publication History Received8 December 2023Published online21 December 2023https://doi.org/10.1021/acsami.3c18419© 2023 American Chemical Society. This publication is licensed under CC-BY. This publication is Open Access under the license indicated. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (629 KB) Get e-Alertsclose Get e-Alerts 

Correction to "Low-Resource Nucleic Acid Extraction Method Enabled by High-Gradient Magnetic Separation".

Achievement of 15-Minute Adaptive PCR Benchmark with 1370 nm Laser Heating

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