Cellular Restriction Factors: Exploiting the Body’s Antiviral Proteins to Combat HIV-1/AIDS
Bibliographic record
Abstract
Introduction 1.1 Overview of HIV-1/AIDS therapiesIn 1983, when researchers first isolated HIV-1 from an AIDS patient, few imagined that it foretold a worldwide pandemic (Broder & Gallo, 1984, Barre-Sinoussi et al., 1983).More than 25 years later, 65 million people have been infected with HIV-1; nearly half of these people have died of AIDS, and despite many scientific advances we are still without an efficacious vaccine (Merson, 2006).The majority of HIV-1 infections and deaths have occurred in developing countries, with sub-Saharan Africa accounting for over 38 million HIV-1 infections alone.Sadly, the number of new infections currently exceeds our ability to treat everyone infected with the virus, and in the hardest-hit countries the social and economic backlash has been profound.After HIV-1 was isolated, a blood test to screen patients and the blood supply quickly followed, as did research on its structure and pathogenesis.Many assumed that a vaccine would be available in a few years, and excitement increased further with the licensing of the first effective drug against HIV-1, zidovudine (AZT) (Fischl et al., 1987).However, researchers soon discovered that the virus was highly resilient, and HIV-1 quickly developed resistance to AZT (Poli et al., 1989, Richman et al., 1994).Over the next few years, a number of new antiretroviral drugs were developed that attacked the virus in different ways, and it was at this time that a new approach to therapy ensued.Highly active antiretroviral therapy (HAART) combined three or more different drugs to reduce HIV-1 replication, and significantly improved the prognosis of HIV-1-infected individuals (Richman et al., 2009).However, HAART was not a cure, and many patients were resistant to at least one of the antiretroviral drugs.In addition, the drugs were highly toxic, making adherence to treatment difficult.During this time, the vaccine field was also hard at work, trying to develop a safe and effective HIV-1 vaccine.Most initial vaccine approaches focused on the HIV-1 envelope protein (gp120), and aimed to induce an antibody response to gp120.AIDSVAX was the first vaccine candidate of this type, and was developed by a U.S. pharmaceutical company called VaxGen (Flynn et al., 2005, Pitisuttithum et al., 2006).An alternative approach, developed by Merck, aimed to induce a T-cell response to HIV-1 using a recombinant adenovirus vector expressing HIV-1 Gag, Pol and Nef proteins (Shiver et al., 2002).Unfortunately, results from www.intechopen.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".