Posts Tagged → #HIVPEP

HIV PEP Drugs: Viread® (tenofovir) nucleotide analogue reverse transcriptase inhibitor (NRTI)

HIV PEP drug - VIREAD TENOFOVIR

Tenofovir (Viread®) was invented by Antonín Holý from at the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and patented in 1984, making this one of the earliest antiviral drugs. In collaboration with Gilead Sciences and the University of California, it was developed into its current form and was approved for use against HIV in 2001. It is now also being used for the Post-Exposure Prophylaxis of HIV.

Viread® is a defective nuclease that lacks the OH- group of the deoxyribose sugar. Because of this lack, when the Viread® particle is incorporated into the DNA strand, no other deoxyribose sugars can be added, terminating production. Viread® does not interact well with human DNA polymerases and so does not have a large effect on normal cell replication. It does interact with the viral reverse transcriptase that changes the viral RNA into DNA, preventing viral replication in the host cell.

Side effects

The most common side effects with Viread® are gastrointestinal upsets such as loss of appetite, stomach ache, nausea, gas, cramping, diarrhoea and vomiting. Patients can also experience a skin rash, insomnia, headaches, dizziness and depression.

Like Emtriva® it can cause lactic acidosis so patients should be on the look out for sore muscles for no reason, fatigue, chills in the limbs and irregular heartbeat or trouble breathing. Lactic acidosis can be fatal if left untreated so it is important to seek urgent medical care should you start to exhibit these symptoms. Be aware this is a rare side effect.

Liver toxicity can occur so watch for jaundice, dark urine, light stools and fatigue. Viread® has also been linked to decreases in bone mineral density so it may be wise to speak to your doctor about supplements while taking Viread®.

Contraindications

People with pre-existing liver damage should be carefully monitored while taking Viread®, particularly those with viral hepatitis.

Lactic acidosis is more commonly seen in females, people who are overweight and those who have been taking HIV medication for an extended period of time.

Alcohol can exacerbate liver conditions so it is best to avoid heavy drinking while taking Viread®. The drug has been shown to increase symptoms of hepatitis for those suffering viral hepatitis B (HBV), though the drug itself has been approved for treatment of the HBV under controlled conditions. Be sure to inform your doctor if you have HBV so that the correct dose can be administered and liver function monitored. Patients with HBV have shown a significant increase in pathological symptoms following discontinuation of Viread® so should be monitored when coming off the course.

Those with a history of osteoporosis or other bone disorders should speak to their doctor before taking Viread®.

There is no evidence to say that Viread® is dangerous during pregnancy but insufficient data to claim it is safe. As a consequence, it should be given only in the utmost need to pregnant women. Viread® is transmitted through the breast milk, as is any live HIV virus and it is advised that those women on Viread® do not breastfeed.

Drug interactions

Due to the method of clearance from the body via the kidneys it is advised that you avoid mixing Viread® with nephrotoxic (nephron=kidneys) drugs. Viread® has not been linked to kidney failure but it is still advised that kidney function is monitored. It is recommended for patients on didanosine that the didanosine is reduced or discontinued while as Viread® will increase didanosine bioavailability which can cause damage to the kidneys or pancreas.

Viread® should not be given along with HEPSERA.

Viread® is not the only drug to contain tenofovir and it is important to ensure the correct dose.  Inform your doctor if you are taking any other anti-HIV medications to prevent overdosing. Often increasing the dose will not increase effectiveness against HIV but will exacerbate the side effects so it is important not to double up.

There is some evidence to show that Viread® bioavailability levels are boosted by the presence of Kaletra® in the patient’s system.

Additional information

Viread® is one of the oldest anti-HIV drugs and as it acts on the DNA itself rather than a protein, resistance is rare though it does occur. It is listed on the World Health Organisations list of essential medicines for the treatment of HIV and has proved its worth in the fight to stem the tide of AIDS.

Recent studies show that Viread® may have a larger role to play than just as an anti-HIV drug.  Patients with HBV have shown a reduction in viral load when taking Viread® and some have been shown to clear the HBV virus entirely from their system when taking Viread®. Despite this FDA has not approved Viread® for treatment of co-infection with HIV and HBV, concerned about the hepatotoxicity (hepato = liver) of Viread®. The situation is very different in Britain where Viread® is the first drug of choice for treating HIV and HBV co-infection.

The jury is still out on which approach is the correct one. This older of the HIV drugs may well give hope to those who are suffering a chronic HBV infection. Hepatitis C can now be cured in up to 80% of cases with correct administration of anti-virals. It may be that a solution to HBV is on the horizon.

For more information see:

WebMD – Viread

http://www.webmd.com/drugs/2/drug-22106-6330/Viread®-oral/tenofovir-oral/details

Gilead Sciences product information sheet – Viread

http://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/Viread®/Viread®_pi.pdf

HIV PEP drugs: Emtriva® (emtricitabine) reverse transcriptase inhibitor

Guid To HIV PEP Drugs - Emtriva

Emtricitabine was developed as a combined effort between Dr. Dennis C. Liotta, Dr. Raymond F. Schinazi, and Dr. Woo-Baeg Choi at Emory university and was patented by Emory through Triangle Pharmaceuticals under the trade name of Emtriva® in 1996. Triangle Pharmaceuticals has been owned by Gilead Sciences since 2003.

Emtriva®™ targets the HIV protein reverse transcriptase. By inhibiting this protein, it prevents the virus from converting its viral RNA into DNA that can be read by the host cell, halting the virus replication process. This drug is now being used in both HIV treatment as well as prevention in HIV PEP therapies.

Side effects

Emtriva®™ has relatively few side effects compared to other anti-HIV drugs. Most common side effects are diarrhoea and other gastrointestinal upsets. Insomnia, fatigue and depression can be associated with Emtriva® in some patients as well as dizziness and headaches. Rashes can occur as the result of a mild allergic reaction and skin discolouration has been seen in some patients, most commonly in those with dark skin and in children.  Like Kaletra®, Emtriva® can cause redistribution of body fat from the limbs to the torso.

The serious side effect of Emtriva® is the rare development of lactic acidosis where toxic lactic acid builds up in the muscles resulting in short-term muscle aches similar to those seen after exercise. This condition, if left untreated, can be fatal and you should consult your doctor if you experience unusual muscle aches along with fatigue and difficulty breathing.

Emtriva® is metabolised by the liver and can cause liver disease. Jaundice (yellowing of skin and eyes) is a sign of liver damage and you should seek medical assistance immediately if you notice any yellowing of skin or eyes. Other signs to watch for are darkening urine, going off your food, nausea, light coloured stools and abdominal pain.

Contraindications

Emtriva should not be taken by those who have shown allergies to drugs of a similar class. This drug is metabolised by the liver and so can exacerbate hepatitis. It is not approved for use in patients with Hepatitis as it may escalate prior liver damage. The same advice is given for patients with kidney disease or elderly patients as Entriva is eliminated from the body by the kidneys and may put added stress on this organ.

Alcohol use should be limited while on Entriva as the breakdown of alcohol will also stress the liver. Patients with Hepatitis should be monitored while on Entriva. While there have been case studies that show Entriva is effective against the Hepatitis B virus, others have seen a severe escalation in liver dysfunction and it is not currently approved for treatment of Hepatitis B.

Lactic acidosis is a rare side effect of Emtriva but is more likely to occur in patients that are overweight, female or who have been taking Emtriva or similar drugs for an extended period of time.

Current studies suggest that Emtriva does not harm a developing foetus and should be safe for use in pregnancy but there is not sufficient data to say it is definitely safe. As such it is suggested that Entriva is used only when absolutely necessary should the patient be pregnant. Entriva is secreted in breast milk and live HIV virus can be transmitted via breast milk even when the patient is taking antivirals.  It is advised that patients taking Entriva do not breastfeed their infants.

Drug interactions

Emtriva should not be taken along with other reverse transcriptase inhibitors such as lamivudine so it is essential you inform your doctor if you are taking any other anti-HIV drugs so they can ensure the correct dose. Other drugs may interact with Emtriva, make sure you inform your doctor of any medication or supplements you are taking.

Additional information

Emtricitabine is listed as an essential medicine by the World Health Organisation (WHO). It is one of the pioneer drugs in the fight against the spread of AIDS and its relatively few side effects and high safety profile make it a drug of choice for nuclease inhibitors.

As it acts against a viral protein that is able to mutate there are strains resistant to Emtriva, notably the M184V mutation (this means that the 184th amino acid in the protein has mutated from a methionine to a valine). Resistant strains are commonly seen in those who have been taking Emtriva or the closely related lamivudine for long periods. Those with resistant strains may need to be put on a different class of nuclease inhibitor such as Retrovir or Viread.

Emtriva has shown some effectiveness in the treatment of Hepatitis B virus (HBV) and some doctors will prescribe Emtriva for patients withHBV. However, due to the exacerbations of liver illness, treatment of HBV with Emtriva can cause symptoms to worsen. It is a case of which is worse, the virus or the effects of hepatitis.  Because of liver toxicity Emtriva is not recommended or approved for treatment of HBV despite possible antiviral properties.

For more information see:

WebMD – Emtriva

http://www.webmd.com/drugs/2/drug-76365/Emtriva®+oral/details#precautions

Gilead Sciences product information sheet – Emtriva

http://www.gilead.com/~/media/files/pdfs/medicines/hiv/Emtriva®/Emtriva®_pi.pdf

HIV PEP drugs: Kaletra® (lopinavir/ritonavir) viral protease inhibitors

Guide to HIV PEP - Kaletra

The HIV PEP designer drug Kaletra® (LPV/r) contains the two HIV viral protease inhibitors lopinavir (LPV) and ritonavir (RTV) [Norvir®]. Developed by Abbott laboratories in 2000, it is referred to as a designer drug as it was specifically formulated based on X-ray crystallography structures to specifically target the HIV protease.

Both lopinavir and ritonavir inhibit the viral protease, but the genius behind Kaletra® is the combination dose that allows the two drugs to work in synergy. Ritonavir has toxic side effects at the levels required for it to inhibit the protease on its own while lopinavir struggles to maintain biological activity in the body. Abbott Laboratories discovered that at low dose ritonavir increases the activity of lopinavir by increasing the amount of the drug that remains biologically active and able to inhibit the HIV protease. The combination drug Kaletra® is able to produce a greater effectiveness at a lower dose for both drugs than they are able to achieve on their own.

Side effects

The lower dose in Kaletra® does reduce the side effects but does not eliminate them. Common side effects from Kaletra® include nausea, headaches, muscle pain particularly in the back, vomiting, dizziness, heartburn, redistribution of weight from limbs to the torso and itchy skin.  Severe and even fatal allergic reactions have been seen with this drug and it is advised to seek emergency medical assistance should a skin rash appear on taking Kaletra®.

Contraindications

Kaletra® like many medications can stress the liver. If you have liver disease you should check with your doctor prior to taking this medication. Yellowing of the skin and eyes (jaundice) is an early warning sign of liver damage. Seek medical assistance should you notice jaundice appearing. Diabetes is another condition that needs to be monitored carefully while taking Kaletra®. Irregular heart beat may occur and patients with pre-existing heart conditions should be closely monitored.

The drug can cause an increase in sugar levels so care should be taken to monitor levels carefully in diabetics. Those who are not diabetic can start to show symptoms similar to diabetes while on this drug. Watch for increased thirst, increase in the need to urinate, fatigue, dizziness, fainting, blurred vision and fruity smelling breath. Hyperglycaemia (too much sugar in the blood) if unchecked can lead to coma and death even if the patient is not diabetic.  Patients with pancreatitis, haemophilia and low potassium levels should also speak to their doctor about possible alternatives.

Pregnancy or breastfeeding should always be discussed with your doctor before starting any new medication. It is not advisable to take Kaletra if breastfeeding and a different dosing strategy is required during pregnancy.

Drug interactions

As well as complicating existing medical conditions and uncomfortable side effects, Kaletra® interacts with other drugs. Your doctor will provide you will a full list should you start taking this drug and you should advice of all drugs you are taking including herbal remedies.  Kaletra® is known to interact with hormone treatments and decrease their efficiency, the pill may not work as well and extra care such as using condoms is advised as contraception while using this drug. Herbal remedies can contain strong drug compounds. It is not advisable to take St John’s wort for example while on Kaletra®. Your doctor or pharmacist can advise you on other herbal remedies that you may be taking.

Additional information

The development of Kaletra® has not been without its share of controversy. The patent held by Abbot Laboratories will not expire until 2016. The expense of the drug led the Thai government to ignore the patent and authorise the import of generic versions in 2007, reported in the Financial Times (By Amy Kazmin in Bangkok and Andrew Jack in London March 17, 2007).  Abbott Laboratories responded by removing their drug from the Thai market, with resulting backlash from global NGOs. Attempts by India to follow suit left them with an inferior product (Financial Times, Andrew Jack, August 1, 2008).

The funds required to research and develop a drug such as Kaletra® are not small. Designer drugs such as Kaletra® where expensive and time-consuming studies are performed are a risky enterprise. Most designer drugs fail, either due to function or to toxicity in human trials. The patent laws are meant to ensure that the company that does the work benefits from the success of the drug. Some argue that this gives the company a monopoly and when that drug means the difference between life and death the company can in effect hold a person’s life ransom with the cost of the drug. It cannot be doubted that companies have done this in the past. From the point of view of the Thai government, they were doing what they thought necessary to save the lives of their people. From the point of view of Abbott Laboratories, they see a drug they have likely spent a decade and millions of dollars perfecting, being given to a competitor for free to profit from. The politics surrounding the global distribution of Kaletra® is a good example of the conflict between the needs of a business to be profitable and the needs of the people for treatment at a reasonable cost.

For more information see:

WebMD – Kaletra

http://www.webmd.com/drugs/2/drug-19939-542/kaletra-oral/lopinavir-ritonavir-oral/details#uses

Kaletra product information.

https://www.kaletra.com/important-safety-information

HIV PEP: Frequently asked questions

What is PEP?

PEP stands for Post-Exposure Prophylaxis and is a combination of drugs (usually lopinavir/ritonavir, emtricitabine and tenofovir) that will prevent replication of the HIV virus long enough for your body to clear it.

How does PEP work?

HIV PEP uses a three-pronged attack, aiming at elements of the virus essential for replication and that do not match processes used in human cells. This way the drugs attack the virus but do not interfere significantly in essential cell processes. It has three groups of drugs, a protease inhibitor (lopinavir/ritonavir), a reverse transcriptase inhibitor (emtricitabine) and a nucleoside reverse transcriptase inhibitor (tenofovir).

HIV is a retrovirus, which means it has an RNA rather than DNA genome. Before it can replicate in the cell it needs to change the RNA to DNA so that the human cell will recognise it and start making copies. To do this, it needs three things, the RNA genome as a template, a protein called a reverse transcriptase that reads the RNA and converts it to DNA and nucleosides/nucleotides (deoxyribose sugars) to make the DNA. The reverse transcriptase inhibitor binds directly to the viral reverse transcriptase preventing it from acting and stopping viral replication. The nucleoside reverse transcriptase inhibitor is a defective deoxyribose sugar that lacks the OH- group on the 3’ end. This prevents any deoxyribose sugar being added to the DNA strand after that point and stops the transcription dead.

The third prong of the attack is the protease inhibitor. If the virus gets past the reverse transcription inhibitors and makes viral DNA, the host cell will convert that DNA into a protein which is the functional element that the DNA is the plan for. This protein (gag-pol) needs to be cut in certain places to go from a pre-peptide to functional proteins. The protease inhibitor blocks the viral protease that cuts the pre-peptide, preventing the formation of functional virus particles. Working together these three elements effectively halt viral replication long enough for the body to clear the infection.

How effective is PEP?

PEP has been shown to clear the HIV from the system in >70% of cases. It is not a cure. It halts viral replication and so decreases the chances that an integration even will occur but will not undo any integration even that has already occurred. These events are very rare and are certain in non-treated HIV cases only due to the high number of virus and the time the body is exposed. The drugs can halt viral replication long enough for the immune system to recover and clear the virus. However, sometimes a recombination even occurs early in the infection and if this happens then the virus cannot be cleared. It is a bit like a game of Russian roulette, the longer you play, the more likely you are to get a bullet, but it can be in that first shot. This is why it is necessary to follow up after the PEP course to ensure the virus has been properly cleared. The only way to completely ensure you don’t get an HIV infection is to avoid contracting the virus in the first place. Practice safe sex with a partner who also practices safe sex.

What are the most common side effects of PEP?

  • Headaches
  • Backaches
  • Dizziness
  • Nausea
  • Vomiting
  • Diarrhoea
  • Insomnia
  • Depression
  • Redistribution of body fat from the limbs to the torso
  • Development of a buffalo hump
  • Irregular heart beat
  • Fainting.

That is not to say you will experience any or all of these, but they are normal to experience while taking this medication. Not all side effects will be listed on the information sheets. If you find you are experiencing a side effect that you can’t find a reference to does not mean it is not linked to the PEP or that you are imagining it.  Only the most common side effects are listed as a rule. Anything you are unsure of please speak to your doctor.

What are the most serious side effects of PEP?

Liver damage seems to be the most common of the serious side effects. Jaundice, darkening of the urine and loss of appetite are the things to watch out for there. Kidney dysfunction is another thing to watch out for and you should speak to your doctor should you find significant changes to your toilet habits following PEP. Lactic acidosis is a rare but serious side effect where lactic acid builds up in the muscles (this is the substance that makes muscles ache after exercise). It can be fatal so seek urgent medical attention if you are suffering unexplained muscle aches, fatigue and dizziness.

One of the components of PEP can raise your blood sugar levels so it is important to keep a closer eye on those should you be diabetic. Those who are not diabetic should seek urgent medical attention should they find themselves exhibiting the symptoms of diabetes – increase thirst, increased urination, dizziness, fainting and fruity smelling breath.

Most of these side effects are rare but given that they can be fatal it is important to be aware of them and to seek emergency medical care should you suspect you are showing symptoms. A false alarm can be annoying, but it is better than ignoring valid warning signs. Make sure that you are having regular follow ups with your doctor during your PEP course, these are serious medications and can do real damage if not monitored correctly. If you have a good doctor, he or she will not mind you asking whatever questions you may have.

Do I need to take the full 28-day course?

Yes. The drugs to do not kill the virus, they stop it replicating. It is your own immune system that clears it and that has come under a significant attack by the HIV. You need to give it time to recover and clear the virus.  There has been lots of research in this field and 28 days seems to give the best outcome.

Do I need to go to the same doctor for check ups?

No, but it is wise that you do so. HIV is a scary disease and the drugs to treat it are very strong, with side effects to match. A good relationship with your doctor can make a huge difference.  It is easier to catch any problems if you are seeing the same person and they have all your previous data. Find a doctor you have confidence in and who you can ask questions of.

Can I take PEP if I am pregnant?

Yes, it is likely that PEP is safe if you are pregnant but it has not been proven that it is safe. Use only if absolutely necessary, but if you do have to use it, it is unlikely that the baby will be harmed.

Can I breast feed if I am on PEP?

No. All the PEP drugs have been found in breast milk so you will be giving them to your baby. You also run the risk of transmitting live HIV virus via the breastmilk. Baby milk formula is the safest choice in this situation.

What do I do if I forget a dose?

Take the dose when you remember unless you are within four hours of your next dose, then continue as normal. Do not take double the dose. It will not improve the effectiveness if you double up, but it will increase the severity of the side effects.

I have flu like symptoms when I take PEP, is this normal?

Yes. It is called Immune Reconstitution Syndrome and it is a result of your immune system recovering from the HIV attack. It is responding to threats that it was too weak to combat before the PEP treatment and is a good sign.  If symptoms are serious, speak to your doctor.

Can I drink alcohol while taking PEP?

It is advised that you don’t. Alcohol is processed in the liver and all the PEP drugs can cause liver damage. Best to give it a rest for 28 days. That said, alcohol will not interfere with the activity of the drug and if you have half a glass at a special occasion it is unlikely to do any harm. Avoid binge drinking, your liver will thank you.

Can I have unprotected sex while on PEP?

No. The PEP drugs inhibit the virus, they don’t kill it. That is why you need to take them for a month. In most cases, your immune system is able to mop up the inhibited viruses before they can integrate into your genome and become chronic infections. Live virus is still present and while the chances of transmitting it are decreased, your blood and body fluids may still be infectious.

What Do We Do If Days Into Treatment, Another Exposure Occurs?

We added this answer based on a question from Quora.

Additional instances of exposure do happen with some degree of frequency. Both during, and immediately after HIV PEP treatment. On the one hand, people don’t always learn their lesson. On the other, there is the drive for sex, and the prevalence of drug abuse, particularly methamphetamine (ice), causing a decline in safe sex practices.

Going by the principle of the HIV PEP treatment protocol, a full 28 days of treatment should be completed after any potential exposure. Therefore, if a potential exposure did occur during treatment, then the end of the treatment should extend till 28 days after the point in time when the exposure happened.

In The News

Pressure in Europe for access to PrEP

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/

Zimbabwean government clamps down on pharmacies

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/

Just as likely to get STD in a monogamous relationship

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

End users’ perspective of HIV PEP

HIV PEP has been a revolutionary treatment that has prevented many who have been exposed to the HIV virus from getting infected. Information, news, scientific findings, views and recommendations have always been coming from healthcare institutions and scientific bodies, but seldom do we get the chance to know views and experiences of end-users who are prescribing PEP therapy. The views of the people using or have used post-exposure prophylaxis (PEP) were recently reported in a publication of the journal “Clinical Infectious Diseases”. This publication was developed by the WHO to help inform recommendations and guidelines for HIV PEP.

Research Methods

The study was conducted by gathering feedback and views from people using or have used PEP. Several methods were used in the study.

  1. Data was collected by searching for papers published online (PubMed and Web of Knowledge) and also searching by hand for articles reporting on HIV PEP outcomes. 10 studies were identified with focus on men who have sex with men while 26 studies were identified that had a focus on healthcare workers.
  2. A review of the recommendations of the WHO was done for this study by two different researchers.
  3. Focus group discussions were done in Ghana related to the preferences, attitudes, behaviors, knowledge, drug regimens, testing, follow-ups and drug adherence in 20 female sex workers.
  4. An online survey was conducted in three different languages in which 306 responses were gathered. The people which took part in the online survey were approached through the help of the authors of PEP published studies and regional WHO and key organizations related to HIV. The healthcare workers who had used PEP were also included in the survey.

Research Results

The results showed that the healthcare workers prefer the use and prescription of a 3-drug PEP based on the cost, availability and overall use. There was no significant difference in the opinion about the overall effectiveness of 2 versus 3-drug PEP.

When it came to online survey responses from healthcare workers with experience prescribing HIV PEP prescription to children, results were quite limited. From the results, there was a trend of using ritoinavir boosted lopinavir as the third drug in PEP when prescribing for children. while Efivirenz was preferred for children 3-10 years of age as the third drug.

Most of the healthcare workers were in favor of prescribing 28-day regimen for PEP. 65% of the respondents were of the opinion that besides HIV specialists, healthcare workers should be able to prescribe the 28-day PEP treatment. More than 86% of the health care workers believed that the Starter Pack is effective. 73% of the healthcare workers who were themselves using PEP preferred to be given 28-day PEP on their first visit.

Conclusion

Surprisingly, access to care was found to be the barrier for completion of PEP which included difficulties in access to the clinics and health care centers.  The respondents emphasized that counseling plays a vital role in adherence to the PEP. The overall follow-up rate, knowledge of potential risks, and completion of PEP is better with counseling.

Although the data presented in this publication encompasses a variety of information but the quantity and quality of data is insufficient to help finalize PEP guidelines. As the information for the report was gathered from a limited population hence the authors believe that these results are not replicable to the general population.

Source:

Beanland RL et al., End user’s views and preferences on prescribing and taking postexposure prophylaxis for prevention of HIV: methods to support world health organization guideline development. Clinical Infectious Diseases,  2015.

A systemic review for choice of HIV PEP treatment on Children with HIV exposure

The Human Immunodeficiency Virus (HIV) is not an adult-only disease but is also known to infect infants and children. The common causes of HIV infections in children are usually accidental needle stick injuries, premastication and sexual assault. Guidelines for adults recommend a base of tenofovir with lamivudine (3TC)/emtricitabine (FTC) and a third drug which is either a protease inhibitor or an integrase inhibitor. However, there is currently a lack of data to help form recommendations for age-appropriate HIV PEP formulations for children of different ages.

A recently published systemic review gathered the published data on the drugs and therapies used for HIV post-exposure prophylaxis (PEP) as well as ART for children living with HIV to make recommendations for the safe use of antiretroviral post-exposure prophylaxis in children. This study was conducted to help establish WHO guidelines on the choice of drugs to be used in PEP for children.

Method

To prepare this report two different systemic reviews were conducted. In one of the works, published data was searched for studies which reported safety and completion rates of PEP in children. In the second review work, published data was searched for to find available evidence on the safety and efficacy of drugs used for antiretroviral medication therapy. The age group selected for the study were children at age 10 or younger – this age range was selected because children above 10 years old are usually given the same treatment as adults.

Results

Completion Rates
For the first part of the study, out of total 97 studies screened initially, 3 prospective cohort studies were selected as per the selection criteria of the study. According to the reports, children in these studies (following injuries from needles in Canada and South Africa as well as sexual assault in Malawi) were given zidovudine and lamuvidine as part of a two-drug PEP therapy. This regimen had a completion rate of 64% in children receiving the medication for 28 days. The percentage of children who discontinued PEP due to adverse effects was 4.5%.

Efficacy and Risks
The second part of the study to evaluate the efficacy of drugs used as NRTI backbones, one randomized trial was identified to be included in the study. This paper compared abacavir with lamuvidine (3TC) and zidovidine with lamuvidine (3TC) and found that the regimen containing abacavir had better efficacy but the study reported one death and 1 treatment discontinuation due to hypersensitivity reaction.

3 studies were included to assess the choice of the third drug for children less than 3-year old. These studies compared lopinavir to nevirapine and found that there was a lesser risk of treatment discontinuation due to reactions when lopinavir was used. It was found that here was no difference in the efficacy of these drugs in children of age more than 3.

Conclusion

This paper concluded that a regimen of limuvidine, ziduvidine and lopinavir is recommended for a three-drug HIV PEP medication to be used on children. The medication should, however, be administered according to the weight of the children.

The alarming thing pointed out in the report is that there is very little published research related to drug efficacy, toxicity and usage in children affected or exposed to HIV. More studies are urgently required in this field so that better recommendations for the PEP of HIV in children can be formulated and tested.

Source:

Penazzato M et al., Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Children: A Systemic Review. Clinical Infectious Diseases, 2015.

 

HIV Pre-exposure Prophylaxis, Post-Exposure Prophylaxis and Early Treatment: An Integration

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.

Adherence to HIV post-exposure Prophylaxis and its Side Effects: A study from Ghana

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.

Post-exposure Starter Pack versus Full 28 Day Prescription for HIV

HIV PEP medication has been helping to greatly reduce the possibility of infection after exposure to HIV. PEP is prescribed for 28 days as a two or a three-drug regimen. It is recommended that PEP therapy starts within 72 hours after HIV exposure. A recently published report compared the efficacy of the 28 day full prescription of PEP versus the practice in which a 3-5 day PEP Starter Pack course is handed over to patients and they are provided with rest of the PEP course at the next visit.

The Starter Pack

PEP Starter Packs are prescribed by some instead of the whole 28-day PEP to

  • help new users get used to the regimen
  • facilitate and encourage adherence
  • evaluate potential toxicity
  • reduce anxiety for worried patients while providing counseling at the same time

About The Paper

This paper is basically a compilation of data available on PEP practices and the outcomes will help inform future World Health Organization (WHO) PEP guidelines.

Two different authors of the paper simultaneously searched online databases for articles, abstracts and conferences available on PEP practices. In case of any disagreement among the two authors a third author helped. Only randomized trials and prospective observational studies were included in the formulation of the results. The reports which did not report PEP duration and had less than 10 individuals with PEP were not included in the study.

The type of HIV exposure, the study population, the number of drugs for PEP and the use of zidovudine / tenofovir along with attendance in follow-up visits were evaluated in the study.

Results

Although the overall result quality of this systemic review were marked to be very low, the results showed that out of the total 3259 titles which were initially selected only 54 studies passed the inclusive criteria. Out of these, 37 studies were about the Starter pack while 17 studies reported results of the full 28 day PEP prescription.

According to the report, Starter packs were usually given for a period of one to 14 days. 47% of the studies done on the Starter pack showed that most were given a 3-day Starter pack.

It is interesting to note that the prescription of a full 28 day PEP was more common among occupational exposure. It was reported that 22.4% of  individuals who were started on the Starter pack PEP refused to complete treatment as compared to the 11.4% receiving full PEP. 6.8% of the subjects receiving Starter pack stopped the medication due to toxicity while failure was 4.2% in people receiving full PEP.  The overall completion rate of PEP was 70% among the people who were prescribed full PEP versus the Starter Pack which was only 53.2%.

Conclusion

In conclusion, it can be inferred that the Starter packs might have some benefits but the overall compliance and adherence is not ideal. Therefore, an early start of full 28 day PEP is recommended.

Source:

Ford N et al., Starter Packs Versus Full Prescription of Antiretroviral Drugs for Postexposure Prophylaxis: A systemic Review. Clinical Infectious Diseases, 2015.