Organized by AfA Singapore & TTSH IIDE, the 10th SAC aims to be a forum for those with an interest in HIV/AIDS to gather together to talk, share, discuss and propose solutions to stop the spread of HIV, remove HIV-related stigmatisation and discrimination, and improve care and support for PLHIV in Singapore.
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Swallowing pills to get medication is a quick, painless and often not entirely effective way of treating disease. A potentially better way? Lasers. In this passionate talk, TED Fellow Patience Mthunzi explains her idea to use lasers to deliver drugs directly to cells infected with HIV. It’s early days yet, but could a cure be on the horizon?
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HIV nPEP visits present an important opportunity to test and manage bacterial STI’s and viral hepatitis in the infected patients.
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United Nations, together with world leaders, non-profit organizations and global advocates, has marked December 1 as World AIDS day. What happened in 2015?
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TED Video: Creating an STD-free generation – presented by Jessica Ladd, the founder of Sexual Health Innovations, an organization that uses technology to improve sexual health.
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HIV holds a great threat to health care workers as constant exposure may lead to accidental HIV infection in previously un-infected individuals. A timely treatment of HIV Post-exposure Prophylaxis (PEP) is a prevention therapy that has been proven to be highly effective in protecting against occupational HIV infection. Due to its potential toxicities though, a substantial amount of people on PEP discontinue treatment. A study published in the BMC Public Health, in June 2015, reported the correlation of the adverse effects of PEP and the adherence to it. The study was conducted amount Health care Workers and Health care Students from the Korle-Bu Teaching Hospital, Ghana.
The cohort study was conducted on healthcare providers who were started with PEP due to HIV exposure from January 2005 till December 2010. A total of 228 exposed health care providers were included in the study. The risk assessment was done according to a preset in-house risk assessment system and with help with the guidelines set by the CDC. The medication was prescribed according to the risk exposure. The combination of lamuvidine/ziduvidine/lopinavir-ritonavir or lamuvidine/ziduvidine was administered in high-risk patients for 28 days. People with medium to low risk were given lamuvidine/ziduvidine for either 28 days or only for 3 days. The patients were followed up with blood analysis at week 6, month 3 and month 6 to check for sero-conversion.
Records of incidences of adverse reactions and adherence levels was maintained through telephone contact on day 3 and day 10 for the people who were prescribed the 3-day regimen. For people who were given a 28-day therapy, follow-ups were performed on day 3, day 10, day 20, day 28 and day 35 after the drug was dispensed.
Adverse reactions information related to the PEP treatment were collected from the participants with the help of a questionnaire. The adherence to the medication was assessed during the follow-up visit also with the help of a questionnaire.
The results were interesting to note as they showed that a total of 51% of the participants who received lamuvidine/ziduvidine for 3 days has a follow-up attendance of almost 65% compared to 90% attendance for those on the 28-day regimen. 52 out of 53 people who were receiving the three-drug medication of lamuvidine/ziduvidine/opinavir-ritonavir followed up. 16 people discontinued their two-drug PEP of lamuvidine/ziduvidine when they were found to be seronegative. Interestingly more than 80% of people reported that the time of their HIV exposure was less than 24 hours.
The highest adverse effects were reported to be with the three drugs PEP for 28 days followed by the two-drug PEP for 28 days. The least side effects were reported to be with lamuvidine/ziduvidine 3-day therapy. The most commonly reported side effect was nausea.
100% adherence to PEP was found with the 3-day lamuvidine/ziduvidine treatment. A significant decrease in adherence was noticed with the lamuvidine/ziduvidine treatment on the 28-day regimen (56 %) and the lamuvidine/ziduvidine/lopinavir-ritonavir combo treatment on the 28-day regimen (62%).
Source:
Tetteh R. A. et al. Adverse events and adherence to HIV post-exposure prophylaxis: a cohort study at the Korle-Bu teaching hospital in Accra, Ghana. BMC Public Health, 2015.
Nut allergies are among the most dangerous of allergies, with a high rate of anaphylaxis. Sufferers know to be wary of what they eat. But how many would think to be wary of what their partner was eating?
In 2007, a woman presented at St Helier Hospital in England was suffering from widespread hives and had difficult breathing. She had a known nut allergy but was careful to avoid foods containing nuts. Her partner was very understanding of the condition and though he ate Brazil nuts, was careful to brush his teeth before they kissed.
After exhausting all other leads and knowing that the couple had sex just prior to her symptoms appearing, the doctors at the hospital arranged an experiment. They had the man eat Brazil nuts again and tested his saliva, sweat and semen in a pin prick allergy test on her skin. Tests of the man’s sweat and saliva were negative, but his semen caused a reaction.
Brazil nuts are actually seeds, produced by one of the tallest trees in the Amazonian rainforests. The large nuts are often found in bags of mixed nuts and contain a high vitamin and mineral content and are thought to have the highest content of the nutrient selenium of any food.
Allergy to Brazil nuts are the second most common nut allergy after peanuts and can be life-threatening. There are six proteins shown to be able to cause allergic reactions in people but the main one is known as Ber e 1. It is a small 9 kDa protein which falls into the category of the 2S albumins, a group of proteins common to seeds. Ber e 1 is resistant to digestion and it is the allergen that is able to pass into semen.
To date, Brazil nuts are the only food allergen known to pass into semen and so be sexually transmitted like any other STD. It is advisable to abstain from eating Brazil nuts for 24-48 hours prior to coitus if your partner is allergic. If you have indulged, a condom will provide protection.
If you want more information regarding this case, it was published in The Journal of Investigative Allergology and Clinical Immunology in 2007, Volume 17, issue 3, pages 189-91 by Bensal, et al. entitled “Dangerous liaison: sexually transmitted allergic reaction to Brazil nuts”.
It does rather spoil the mood, having to stop and search for the small package. It invariably ends up at the bottom of the bag or is not in the pocket you thought it was in. Then you can’t get the wrapper undone. There is fumbling. It is clumsy when you want to be sexy. It is plastic, when you are looking for real and intimate. It is not just a barrier to STDs.
But it doesn’t have to be that way. In fact, if used properly a condom can be sexy. It doesn’t have to say casual sex, it can say I care enough to protect you. It doesn’t have to be clumsy, it can be foreplay.
Far from being the sign of a casual liaison, it can show you are well prepared. It is not a good idea to brag about it on a date, but having it in easy reach when things do get steamy will stop it disrupting the flow. Know how to put it on, women I am talking to you as well as men. Practice ahead of time so that when you do need it, it can be done smoothly. The very first thing to do is to learn how to wear it properly. Here is one useful video from plannedparenthood.org:
This would seem to be a no-brainer, but most men who find condoms uncomfortable are using the wrong size. Too large and it can leak and then can result in the spread of STDs or the even more dreaded unplanned pregnancy. Too small and it can be painful and prevent orgasm. Find your size by using the method outlined at http://luckybloke.com/pages/find-your-condom-size.
A wide variety of sexual lubricant is available and most are found beside the condoms in stores, or more specialised ones can be ordered from adult websites. Avoid ones containing spermicides as they are often irritating. The condom is generally sufficient to prevent pregnancy and spermicide does not increase their effectiveness to any significant degree. A drop inside the condom will make it easier to apply and increase enjoyment for the male. Applying it on the outside will prevent friction and increase enjoyment for both partners.
Make the condom part of the fantasy. Get your partner to help apply it during a massage. Foreplay not only increases the intensity of the sex but also builds the relationship. Foreplay teaches both partners what the other likes and improves the sexual side of any relationship.
Condoms are a huge business and the variety is astounding. From glow in the dark, to flavoured to ribbed designs you can pretty much get a condom for any occasion. Far from being a hindrance they can add spice and surprise to your sex life. If you don’t feel comfortable browsing in the store you can check out the different types at http://www.condoms.com.sg/
Remember that condoms do not protect against all STDs and they can fail. There are other preventive methods including staying faithful in a monogamous relationship, abstinence, going on HIV PEP therapy if you engage in high-risk sexual activities. But even in a faithful relationship, a condom can add spice rather than spoil the mood when used correctly.
When it comes to diseases that have shaped world history you cannot go past Tuberculosis (TB). Its footprint lingers in literature, it is found in ancient Neolithic remains and Egyptian mummies and we can even link the development of Kellogg’s Cornflakes with the health crazes that it triggered over the previous two centuries.
TB is caused by the bacterium Mycobacterium tuberculosis, in the same genus as the bacteria that cause leprosy, another scourge of the ancient world. M. tuberculosis bacteria invade the body then concentrate in tubercles otherwise known as granulomatous lesions, cysts which are formed around infected tissue by the immune system. While these halt the immediate invasion and minimise tissue damage they do prevent the immune system or certain antibiotics from destroying the bacteria within allowing it to maintain chronic infection. Its slow growth and aberrant cell wall structure allow the bacteria to be further resistant to treatment. Antibiotics find the cell wall, a cross between gram negative and positive structures, difficult to permeate, and many, including penicillin, target the cell replication process. Treatment required a mix of multiple hard hitting antibiotics over at least six months, a schedule that is often not maintained by patients.
M. tuberculosis shows a preference for the lungs but can invade any body tissue including the brain. Military Tuberculosis is when it gets into the blood stream to cause a systemic infection and is often rapidly fatal. Once a rare complication of Tuberculosis, seen mostly in young children, co-morbidity (infection of two or more pathogens) with AIDS results in a 3-6 fold increase in the risk of developing Military Tuberculosis if infected with the bacteria. More commonly the chronic infection causes scarring of the lungs, leading to a slow death from lung failure.
By the start of the 1800s, it was estimated one in four deaths in England was caused by Tuberculosis. The Victorian’s love of tragedy introduced the consumptive beauty into literature, the heroine who slowly succumbed to a disease that made her pale, thin and ethereally lovely. Diseases were considered the result of miasma (bad air) and health resorts became the rage across Europe and America. In Germany and Switzerland health spa tourism was born. In England, it was Bath and the seaside resorts of Brighton and Hampton that benefited. In America, Dr Kellogg’s health sanatorium focused on nutrition, exercise and strangely enemas. The breakfast cereal he developed was wildly successful. His enema treatments not so much.
By the end of this century, the microscope had revealed the cause of infectious disease. This was the age of Koch and Pasteur, the fathers of microbiology and two of the most bitter rivals in scientific history. It was German Robert Koch who identified the M. tuberculosis, a discovery that won him the Nobel prize in medicine in 1905 and lead to M. tuberculosis being commonly called Koch’s bacillus. Public health campaigns started up to prevent the spread the results of that we can still see today. Laws prohibiting public spitting can be traced to anti-tuberculosis campaigns and the signs from the 1920’s campaign prohibiting spitting are still in place at Melbourne’s famous Flinders St train station. Frenchman Louis Pasteur put his own mark on the history of tuberculosis by developing the method of pasteurisation by which milk could be sterilised prior to sale. Pasteurisation stopped the transmission of the closely related bacteria M. bovis from cows to humans, a common cause of TB in the 1900s.
By the 1940s to 1950s antibiotics had come onto the scene and were successful in causing a rapid decrease in the rates of TB. However, M. tuberculosis was quick to fight back and due to its unique cellular quirks was one of the first bacteria in which antibiotic resistance was seen. The emergence of antibiotic resistant TB strains coincided with the sexual revolution and the explosion of AIDS onto the world, first in Africa in between 1950-1970 then into Asia and the western world.
So why should AIDS and TB be linked? After all of the 1.45 million deaths caused by TB in 2013 (second only to AIDS as the leading cause of infectious disease-related deaths worldwide) only 0.34 million were HIV positive. Yet HIV is listed as a risk factor for TB.
Firstly there are the shared risk factors. Poverty and drug use, which are risk factors for contracting HIV, are also risk factors for many other diseases including TB. TB, like most respiratory diseases, is spread through close personal contact and kissing during sex, like a cold. Secondly, bacteria are primarily opportunistic pathogens. They cause disease for the most part in sick people where the immune system is not so strong and you can’t get all that much more immunocompromised than AIDS. People with compromised immune systems are also more likely to have asymptomatic TB and so spread the disease more readily as they will not take measures to protect their partner. Then there are the drugs, medical drugs I mean. I spoke in an earlier blog piece about how the recent development of one pill HIV PEP combination therapy for HIV was a godsend for doctors as it make people far more likely to take their medication. The same is true for TB.
Imagine that you have AIDS. You are taking three drugs for the HIV, another two to counter side effects, one for the thrush in your mouth, one that you are not sure what it does but your doctor says you have to take it. Then you are told, “Oh and by the way, you have TB. You need to take isoniazid for six months so here are some vitamin B tablets as well and I will also put you on rifampicin. Two months on pyrazinamide, it may cause some joint pain, and ethambutol, now that may cause red-green colour blindness, unlikely, but let me know if you have any trouble with your eyes, ok. Here are some tablets for the diarrhoea this is likely to cause and now I should let you know all of these can cause your liver to shut down, only sometimes, but I will need to you come in for a liver test next month. These need to be taken with food, this one can’t be taken with food, this one twice a day, only take that one in the evening” and so on. I suspect like me you would have trouble keeping them all in order let alone taking them all.
The problem is that non-compliance with the treatment is what causes resistance. There are some superbug strains of M. tuberculosis which nothing will cure, and with a fatality rate of around 50%, that is a scary thought. Compliance programs, where a nurse comes to your house and watches over you while you take your drugs, have been very effective. However, such programs are very expensive and when the highest incidence of TB is in the third world, such programs are just not feasible. You can see why combination therapy for HIV is a wonder. Reducing that list by two drugs makes everything seem far more manageable.
HIV and TB are both diseases of poverty. They occur most often in the marginalised and those who court risk. But their impacts are felt by all. The AIDS 2031 Cost and Financing Working Group, as part of the Joint United Nations Programme on HIV/AIDS (UNAIDS) Global Resource Needs, estimates that by 2031 HIV may be costing the global economy $35 billion dollars US. TB while less in incidence has not had the global research on reducing costs and is estimated to cost $1-3 trillion a year and can rob a country of up to 7% of its GDP. For both diseases are seen primarily in people of working age, resulting in not only direct costs to the health care services but in the reduction of effective workforce.
The good news is that as they are both seen in the same demographic, resources can be targeted to that demographic for both diseases and share the costs. The chronic condition of TB makes it economically viable for drug companies to research and manufacture combination therapies for TB, whereas they are not for other bacteria diseases. Less arduous treatment options mean that compliance going forward is less costly and more likely without a nurse to hover over the patient’s shoulder.
A vaccine, the bacille Calmette-Guerin (BCG), exists, however causes the patient to give a false positive for blood tests for TB. For this reason, the vaccine was not introduced into the childhood immunisation programs in the USA, though it has been used and still is used in many countries including Singapore and Australia. Australia discontinued immunisation against TB in the 1980s except for children less than six months who would be living in or travelling through a country with high TB incidence. TB incidence has been on the rise in Australia since 2007 as with many first world countries, thought to be a result of increased global migration.
Singapore discontinued the second vaccination for BCG in 2001 following a highly successful campaign with the Singapore TB Elimination Programme (STEP) which saw a 15% reduction in new cases of TB in three years. Infants are still vaccinated and this protects them during the most vulnerable years and the second vaccination is deemed unnecessary save in specific high-risk circumstances. Vaccination of children under six months of age does not cause them to show a false positive in TB tests, leaving the current TB detection tests effective. Research is ongoing for a workable adult vaccine.
Co-morbidity is rare for infectious disease except in STDs. Unfortunately if you have one STD it is likely you also have another, and that list is not just limited to STDs. Singapore is fortunate to have a relatively low incidence of both AIDS and TB. If you are travelling be aware that other countries are not so fortunate and activities that may be fairly low risk in Singapore or Australia may be high risk in China or Africa. Make your doctor aware of any other symptoms you may have as well as regions you have recently visited. These things can be treated if you catch them early. Don’t become a statistic.
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.