Health News: College Campuses receive HIV Awareness from Love Heals Advocates, HIV Progression spotted on Charlie Sheen from Facial Skin Lesions, Recent Progress against Aids Marked in World AIDS Day at Palm Springs
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An extremely informative video on the science of HIV and AIDS made by AsapScience on Youtube
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In the news -Today reports better Life For Singaporean HIV Patients; Highest cases of HIV in Eastern Europe reported by WHO; The CDC in the US says HIV Prophylaxis can help millions
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At the 15th European AIDS Conference, speakers voiced concerns from public about the growing need for access to PrEP (Pre-Exposure Prophylaxis) to be used informally. PrEP is a treatment that uses anti-HIV medication to prevent people who are HIV-negative from becoming infected in the near future (up to about 3 weeks after). In Europe currently, like many other countries, PrEP is not funded by government bodies and can only be obtained privately from doctors on an individual basis rather than being a part of the public healthcare system – which means access is limited and more costly.
Many have sought to go around this issue by asking for HIV PEP (Post Exposure Prophylaxis) medication instead with the intention of using them as PrEP. There are national initiatives to push for making PrEP a part of HIV prevention strategies on national levels that is also fully funded, though it is still at an early stage, and moving at a slow pace. Much of the obstacles to making this medication part of the public health system in Europe is due to cost, government red tape as well as the difficulties of implementing something across a continent with varying public health systems.
Read full news report here: http://www.aidsmap.com/When-will-Europe-get-PrEP/page/3008966/
HIV PEP in Zimbabwe is usually only prescribed to medical professionals and workers who have a high risk of occupational exposure and rape victims. This essentially makes access limited to members of the public who engage in risky sexual behaviour. Many, however, are circumventing this problem by obtaining PEP medication from pharmacies that are illegally dispensing such medications without a doctor’s prescription. Pharmacies caught doing so are subject to penalties and sanctions by the Government. HIV PEP is not considered a preferred HIV prevention strategy in Zimbabwe and is strictly dispensed only to rape victims and medical personnel.
Read full report here: https://www.newsday.co.zw/2015/10/02/govt-warns-unscrupulous-pharmacies/
A recent study published by The Journal of Sexual Medicine revealed that individuals in a monogamous relationship are statistically just as likely to contract sexually transmitted diseases as those who are not. In the study, 556 volunteers were recruited, out of which 351 were in monogamous relationships while the rest were in open relationships. Results concluded that the likelihood of contracting STDs were the same between the 2 groups, mostly due to one or both of the parties secretly cheating, which makes us think – is monogamy just an illusion?
Read full study here: http://www.medicaldaily.com/trust-no-one-youre-just-likely-get-std-monogamous-relationship-you-are-open-one-358538
With advancements in the field of research and scientific probing, we are continuously getting better treatments and vaccinations for different diseases. Although, there are currently no vaccines which can prevent HIV, scientists have been able to formulate the next best thing – HIV Pre-exposure Prophylaxis (PrEP). A report by the Center of Diseases, Control and Prevention compiled the recommendations and loopholes in the HIV research from published data on PrEP and HIV Post-exposure prophylaxis (PEP) to find a set of best practices for integrating these 2 highly effective HIV infection prevention methods.
Two effective regimens for the prophylaxis of HIV are PEP and PrEP. PEP is administered to individuals who have been exposed to HIV within 72 hours of exposure. Although, ziduvidine alone is effective in 80% of the time if administered within initial 72 hours, a 2-3 drug medication is recommended by the US Public Health Service in 2013. PrEP, on the other hand, is recommended for people who are living a high-risk sex life, even for those who are already on PEP and have been tested HIV negative. PrEP medication usually includes emtricitabine/tenofovir didoproxil fumarate and is effective in high-risk patients. In contrast, an early treatment regimen is offered as soon as the patient is found to be seropositive after exposure.
According to this report testing for HIV is still critical. HIV testing is recommended in all the cases especially when there is known or suspected exposure to HIV even when on a PrEP regimen.
The key element for the decision to start PrEP, PEP or early treatment after an exposure is dependent upon the antibody titer. Unfortunately, this test is not a good indicator for acute HIV infection where HIV RNA testing is recommended instead. The report says that HIV antibodies might not be detected using the antibody test during an early Acute HIV infection thus resulting in false assurances to the indivdual. This may lead to HIV-positive individuals starting on PrEP which may lead to drug resistance. A 4th generation test for HIV p24antigen can help if the test for HIV RNA is not available. This test has an advantage over 3rd generation and 2nd generation tests as it can detect HIV antibodies way earlier. Furthermore, the report suggests that the signs and symptoms can also guide the physician towards making a decision about acute HIV infection. Fever, myalgia, fatigue, skin rash and headache are common complaints in people with acute HIV infection.
According to the report, for individuals with a significant history of exposure, PrEP should be started even without the results of HIV testing. A single drug for PrEP and a three-drug regimen is recommended for PEP in US. After the completion of a HIV PEP regimen, it is recommended to start PrEP in people engaging in a high-risk sex life e.g. people with multiple sexual partners. The recommended test after 4 weeks of PEP is the 3rd or 4th generation HIV test as HIV RNS testing might be suppressed with a prophylactic treatment of HIV.
For PEP treatments, HIV testing is recommended at day 0, day 28 and 3 months after PEP. In the case of PrEP, testing is recommended at the start. Another test can be done after the first month on a PrEP treatment. Anyone on either PEP or PrEP treatment should be quickly started on early treatment if their blood shows seroconversion.
Source:
Grant M. R. and Smith K. D. Integrating antiretroviral strategies for HIV prevention: post- and pre-exposure prophylaxis, and early treatment. Open Forum Infectious Diseases Advance Access, 2015.
In the 1980’s diagnosis with HIV was a death sentence. In 1995 in the USA, it was the highest cause of death in the age range 25-44 years. Nowadays HIV is a life sentence, but a relatively painless one. Anti-retroviral therapy (ART) has ensured that the virus is kept locked away in the host DNA, never to be seen more in most cases.
From no treatment available in 1983 to more than 40 retroviral inhibitors in 2015, with more in the works, scientists are staying one step ahead of emerging resistance. The death toll from HIV continues to plummet. Anti-retrovirals consist of a wide range of drugs that target different stages of the virus lifecycle.
The first thing the virus needs to do to effect a successful infection is get into the cell. This stage is thwarted by the entry inhibitors, notably maraviroc (MVC) and enfuvirtide (T-20).
Maraviroc binds to the host cell receptor that the HIV virus binds to before working its way into the cell. It is not a common treatment. The binding of Maraviroc to the cell can open up a secondary binding site, allowing the HIV to attach regardless. The drug also has liver toxicity issues. It has however been approved by the FDA for human use and is a fallback when other drugs prove ineffective.
Enfuvirtide acts on the virus rather than the host cell, binding to the gp41 protein that HIV uses to attaches to the cell, inactivating it and stopping invasion of the cell before it starts. As with Maraviroc, it is used as a ‘salvage therapy’ rather than the first port of call due to its high cost and the fact it can only be administered as an injection.
HIV is a retrovirus, which means that the virus genome is made of RNA rather than DNA. In order to replicate it needs to transcribe the RNA code into the DNA used by mammalian cells for genomic content. Mammalian cells only transcribe DNA to RNA, not the other way around. The protein needed to transform the RNA into DNA has to be provided by the virus. It makes a good place for scientist to target as the fact that it is not a protein seen in humans reduces the risk of side-effects.
The Nucleoside (or Nucleotide) analogue reverse transcriptase inhibitors (NRTI). NRTIs are specialised nucleosides, the building blocks of DNA, lacking the essential hydroxy group on its 3’ end. Lack of this group prevents it from binding to another nucleoside and stops the construct of the DNA strand cold. Without this DNA strand the virus is unable to trick the host cell into replicating viral the viral genome. The NRTIs are the most effective anti-retroviral therapies and include some of the oldest anti-retroviral among their number. Examples include zidovudine (ZDV), abacavir (ABC), lamivudine (3TC), emtricitabine (FTC), and tenofovir (TDF).
Non-nucleoside analogue reverse transcriptase inhibitors (NNRTI). NNTRIs are drugs that target the viral reverse transcriptase directly rather than targeting the process. By binding the viral protein near the active site they change the structure of the active site, so it cannot bind nucleosides and catalyse the formation of DNA from the RNA viral genome. Examples include nevirapine (NVP), efavirenz (EFV), etravirine (ETR) and rilpivirine (RPV).
The virus is not able to change the building blocks of DNA so resistance to NRTIs is uncommon, however, it can change the structure of the reverse transcriptase protein. HIV-2 is naturally resistant to NNRTIs.
A viral infection that destroys all the cells it is able to infect does not have a long lifespan. To ensure it lives to fight another day, the virus does not destroy all the T-cells in invades. In some instead of taking over the cellular machinery to make thousands of copies with the transcribed DNA, it inserts its own DNA into the host cell genome using a viral protein known as an integrase.
In 2007, the drug raltegravir (RAL) was approved by the FDA. Raltegravir binds in preference to the native substrate, i.e. if there is any raltegravir nearby the integrase will select that before the host genome it is meant to target. In this way, it uses up all the integrase before the virus can insert into the genome. In 2014 two more integrases inhibitors were approved for use, elvitegravir (EVG) and doultegravir (DTG).
Once the viral DNA has been transcribed and integrated the virus needs to then make more copies of itself. It does this by tricking the host cell to replicate the viral RNA genome and proteins in preference to its own functions, killing the cell in the process. The viral proteins are made as one long peptide (protein) chain called the gag/pol precursor and this is cut up by a viral protease (enzyme that cuts proteins) to separate the individual proteins into their active form.
The protease inhibitor antiretroviral drugs target this stage of the virus lifecycle, preventing the protease activity and activation of viral proteins. Protease inhibitors include lopinavir (LPV), indinavir (IDV), nelfinavir (NFV), amprenavir (APV) and ritonavir (RTV). Due to high mutation rates of the viral genome and high tolerance for mutation in the viral protease, this category of drugs suffers the most from emerging resistance.
The drugs are used as combinations to target multiple stages in the viral cycle and reduce the incidence of resistance. They are used in combination to target the virus at all stages of infection, commonly 2 NRTIs in combination with either a NNRTI, a protease inhibitor or an integrase inhibitor.
Different combinations are preferred for different situations. One of the earliest NRTIs Zidovudine (first approved 1989) has been shown to be incredibly effective in reducing the viral load in pregnant women to prevent transmission to the baby during birth. Use of Zidovudine has reduced transmission of HIV to the baby during birth from 30% of cases down to 2%.
The pre-exposure prophylaxis (PrEP), taken by those at high risk of encountering HIV is a combination of tenofovir and emtricitabine marketed as a one dose combination therapy under the name of Truvada® by Gilead Sciences. This drug has been shown to be safe for people ages 12 years and older and in various studies have shown that a daily dose reduces the risk of contracting HIV by up to 75% in high-risk individuals. Truvada is also recommended for post-exposure prophylaxis (PEP) though this can vary depending on doctor, socio-economic considerations and regional resistance, other combination therapies can be equally effective.
The first one dose combination therapy was developed by GlaxoSmithKline in 2007. Called Combivir® it contained a combination of lamivudine (3TC) + zidovudine (ZDV). As of February this year, eleven other single dose combination therapies had become available. This may seem a small breakthrough but it increases the likelihood that people will continue to take their medications and stay virus free, reducing the costs to the healthcare system, increasing peoples work life and reducing the risk of spreading via sexual contact. These miracle pills did what antibiotics did in the 1950’s, turned a killer into a mere inconvenience. With ongoing research this inconvenience lessens each year and with the blessing of hindsight we know how to reduce the threat of resistance. With good management, extensive education and ongoing research, AIDS may one day join smallpox and polio as a disease of interest only to historians.
Like vaccinations for life-threatening diseases such as Hepatitis B and Tetanus, the HIV virus could be tackled more efficiently with the presence of a vaccination for this disease. Researchers have been successful in developing a pre-exposure prophylaxis (PrEP) for HIV which is now a leading development towards finally creating a vaccine. Pre-exposure prophylaxis is a combined treatment for the HIV retrovirus that is efficient in protecting people exposed to HIV from developing an infection. This information was very recently reported in Clinical Infectious Diseases, a scientific journal dedicated to infectious diseases.
HIV post-exposure prophylaxis (PEP) which has been in use for a long time, is given to individuals within 72 hours of an exposure to HIV. PEP is a 28-day medication that is a combination of 2-3 antiretroviral drugs. Studies have shown that patients receiving PEP are still at a higher risk of acquiring HIV. People who have a continuous exposure to HIV like injection drug users and people having multiple sexual partners are recommended to use PrEP. PrEP users are reported to have a lower risk of acquiring HIV when compared to PEP. It is, however, highly recommended to avoid the risk of exposure altogether.
The regimen for the PrEP is tenofovir-emtricitabine. This is the only combination approved by the FDA, USA, for PrEP at the moment. It is given either daily or intermittently for a longer period of time, unlike PEP.
People who have already been administering PEP and have a seronegative profile for HIV retrovirus are candidates for PrEP. According to CDC PEP guidelines, a person who has been exposed and administered with PEP can only be considered infection-free after a six-month HIV testing protocol. These candidates who have had PEP and are seronegative will benefit best with PrEP. People who continue to have high-risk exposure to HIV should be started with PrEP earlier than the 4-6 months profile for HIV.
More recently, the US Public Health Service guidelines suggest that if the HIV profile is negative in the preceding 4 weeks and the person is not having any signs and symptoms for HIV he/she can be started on PrEP.
One interesting question addressed by the report is who will be prescribing PrEP to patients. As there is no consensus to date for the specific position which should prescribe PrEP, it is currently prescribed by emergency care departments, the primary physicians and of course by HIV specialists treating the disease.
Although the side effects of PrEP and PEP are not very debilitating, PrEP should be administered with care in patients with bone diseases and renal insufficiency. The use of the tenofovir-emtricitabine combination is known to cause osteopenia, a condition in which bone mass decreases. Patients infected with Hepatitis B should be monitored closely for fulminant acute hepatic failure due to PrEP.
With PrEP, a 3-6 month screening for STI is recommended, especially for people living a high-risk sexual lifestyle.
Source:
Jain et al. The Transition From Postexposure Prophylaxis to Preexposure Prophylaxis: As Emerging Opportunity for Biobehavioural HIV Prevention. CID, 2015.