A Systematic Approach To The Patient With Multidrug Resistant Virus
First, the physician needs to identify where the patient is in the spectrum of HIV disease. This will include a full medical history and physical examination to identify past and present HIV-related symptoms and AIDS-defining conditions. A thorough review of all available laboratory results, particularly CD4 cell counts, since the time of HIV diagnosis is also needed to assess the rate of CD4 decline and the individual’s CD4 nadir. This information is essential to assess the urgency of treatment. Immediate switch to a salvage regimen is warranted in patients with a prior AIDS defining illness, or CD4 nadir below 200/mm3 for the absolute count or 15% for the CD4 fraction. Asymptomatic individuals without a history of AIDS-defining illness and with a CD4 nadir in excess of 200 cells/mm3 do not have an immediate risk for disease progression or death and therefore they may be encouraged to defer salvage therapy as long as they tolerate a drug free interval with very close monitoring, even in the presence of a high viral load.37 Such patients should be offered treatment if symptoms develop, or the CD4 cell count decreases below 200/mm3 or if the CD4 fraction decreases below 15%. However, CD4-guided treatment interruptions remain controversial pending results of further studies.
Erik De Clercq, in, 2013
Pretreatment Hiv Drug Resistance
Drug resistance can be found in some people before they begin treatment. This resistance can either be transmitted at the time of infection or acquired during previous treatments, for example in women given antiretroviral medicine to prevent mother-to-child transmission of HIV.
WHO recommends surveillance of HIV drug resistance in adults initiating or reinitiating ART and in treatment naive infants initiating ART to inform optimal selection of first-line regimens.
Up to 10% of adults starting HIV treatment can have drug resistance to the NNRTI drug class. Pretreatment NNRTI resistance is up to 3 times more common in people with previous exposure to antiretroviral drugs. The prevalence of drug-resistant HIV is high in children under 18 months of age and newly diagnosed with HIV. Based on surveys conducted in 10 countries in sub-Saharan Africa , nearly one half of infants newly diagnosed with HIV have NNRTI resistant virus before initiating treatment.
The global prevalence of NNRTI resistance in adults and infants emphasizes the need to fast-track the transition to WHO-recommended dolutegravir-based treatments.
Hiv Medication Side Effects Are Most Common In The First Few Weeks
With today’s medications, most people don’t notice much of anything when they start treatment. Others have a minor side effect or two that will dissipate over the first few weeks. Still others have severe side effects that can make daily life harder or become a health risk they may go away after a few weeks, or they may persist.
If you get a new symptom after starting treatment that becomes worse or doesn’t go away, it’s important to bring it to your HIV care providers attention quickly. There might be blood tests to run or further discussions you can have that will help determine whether its definitely the HIV meds causing the problem, and what you can do about it.
If the symptoms are related to one of your medications, switching to a different medication will likely alleviate the side effect and any health risks.
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Potential Limited Effects Of Current Drugs
In 2004, one study estimated the percentage of the American HIV positive population with some form of drug resistance to be 76.3%. A more recent study in South Korea estimated that 50% of their HIV positive population had multi-drug resistant strains of HIV, while 10% had multi-class resistant strains. Multi-class resistant strains pose a larger problem because each class includes many drugs, and eliminating use of an entire class of drugs severely limits treatment options. These studies indicate that the incidence of resistance varies greatly based on geographic location.
In their 2017 HIV Drug Resistance Report, the World Health Organization conducted surveys in 14 countries to estimate the prevalence of resistance to HIV medications. One subgroup included only HIV-positive patients who had just initiated antiretroviral therapy in order to assess the prevalence of HIV drug resistance in treatment-naive patients, deemed “pretreatment drug resistance.” Resistance to NNRTIs in this patient population ranged from 2.7% to 15.9% . Resistance to NRTIs ranged from 0.3% to 6.8% . Resistance to protease inhibitors ranged from 0.3% to 2.6% . Resistance to NNRTI + NRTI combination therapy ranged from 0.2% to 4.6% .
How To Know If Your Hiv Treatment Is Working
HIV treatment can become ineffective for a number of reasons. Here’s what you need to know about HIV treatment failure and how you can help prevent it.
Current treatments available for the human immunodeficiency virus are very effective, allowing people with the virus to live long and relatively healthy lives. However, sometimes your specific treatment can start to fail, which can raise your viral load and trigger symptoms. Its important to know the signs of treatment failure and what you can do to help prevent it.
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Alarming Surge In Drug
Antiretroviral drugs stop HIV from replicating in the body.Credit: Siphiwe Sibeko/Reuters
Health authorities have uncovered an alarming surge in resistance to crucial HIV drugs.
Surveys by the World Health Organization reveal that, in the past 4 years, 12 countries in Africa, Asia and the Americas have surpassed acceptable levels of drug resistance against two drugs that constitute the backbone of HIV treatment: efavirenz and nevirapine.
People living with HIV are routinely treated with a cocktail of drugs, known as antiretroviral therapy, but the virus can mutate into a resistant form.
The WHO conducted surveys from 2014 to 2018 in randomly selected clinics in 18 countries, and examined the levels of resistance in people who had started HIV treatment during that period.
More than 10% of adults with the virus have developed resistance to these drugs in 12 nations . Above this threshold, its not considered safe to prescribe the same HIV medicines to the rest of the population, because resistance could increase. Researchers published the findings this month in WHO report.
I think we have kind of crossed the line, says Massimo Ghidinelli, an infectious-disease specialist at the Pan American Health Organization in Washington DC.
Overall, 12% of women surveyed had a drug-resistant form of HIV, compared with 8% of men.
doi: https://doi.org/10.1038/d41586-019-02316-x
How To Reduce The Risk Of Resistance
- Take your HIV treatment exactly as prescribed.
- Maintain an undetectable viral load. If you have an undetectable viral load, your HIV cannot become resistant to the anti-HIV drugs that you are taking.
- Take a resistance test before starting HIV treatment for the first time, or before changing treatment. The results will help you and your doctor to choose the combination of medications that is likely to be most effective against your HIV. Theres more information on resistance tests below.
- Be honest with yourself and your doctor about the way you live your life. If its likely that you wont take your HIV treatment properly, then its important that your doctor knows this. This will allow your doctor to prescribe a combination of anti-HIV medications that has a lower risk of resistance. For example, HIV treatment that includes an integrase inhibitor or a boosted protease inhibitor has a lower risk of resistance than treatment that is based on an NNRTI.
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Poor Adherence Gives The Virus A Survival Edge
HIV therapy is taken daily to ensure that you have enough of the drugs in your system to suppress the virus to undetectable levels. They do not kill the virus but rather prevent it from replicating.
If you don’t take your drugs regularly, the levels in the bloodstream will begin to drop and allow the virus to replicate anew. While newer drugs are more “forgiving” and allow for the occasional missed dose, poor adherence still remains the primary cause of treatment failure.
In fact, according to research from John Hopkins University, fewer than 60 percent of Americans on antiretroviral therapy are able to achieve or sustain an undetectable viral load.
What Can Be Done If I Develop Resistance
If you have developed resistance to your antiretrovirals, your doctor will need to look at your treatment history and the results of a drug resistance test to decide the most suitable combination of drugs for you to take.
There are now a number of anti-HIV drugs that work against a version of the virus that is resistant to other drugs.
The recommended options for people who are resistant to the three main classes of drugs NRTIs, NNRTIs and protease inhibitors are as follows:
- the protease inhibitors darunavir and tipranavir
- the NNRTI etravirine
- the integrase inhibitors raltegravir , elvitegravir and dolutegravir
- the entry inhibitor maraviroc
- the fusion inhibitor enfuvirtide .
These drugs are most effective when used in combination with another drug that is active against HIV. Your doctor will look at your previous drug history and do a resistance test to find out which would work best for you.
It’s very important that your new combination of drugs is taken properly. If not, you may develop resistance to those too, and this could mean that your HIV becomes very hard to treat.
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Will I Get Drug Resistance If I Miss A Dose
In general, if you forget to take a dose, take your medications as soon as you realize youve missed the dose. However, if its almost time for your next dose, just wait until your next dose and continue your regular routine. Most important, do not take a double dose you cannot make up for a missed dose that way. Although its important to take your HIV medications every day, you likely will not develop drug resistance from missing just one medication dose.
Hiv Drug Resistance Transmission Surveillance
Studies assessing the prevalence of HIV drug resistance among untreated patients show large discrepancies. Geographical differences, differences in study population, duration of HIV infection, transmission mode, gender or race make comparison between these studies often very difficult. Also, the use of different resistance assays and different interpretation methods give variable results. In addition, most performed studies are retrospective in design and study small numbers. Worldwide, several efforts have been made to standardize these studies. Within the SPREAD project, for instance, clinicians, virologists, and epidemiologists from European countries work together to implement a structured and quality controlled European surveillance program. The aim of the program is to determine the prevalence of resistance transmission within the different risk groups and to identify risk factors enhancing the risk of transmission in a prospective and representative way.
Susan L. Gillespie, … William T. Shearer, in, 2013
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How Bad Is Drug Resistance Is It Something I Should Worry About
Mostly no major harm is done if someone develops or even acquires drug resistant HIV. Usually there are other meds that will work, said David Alain Wohl, MD, a professor in the Division of Infectious Diseases at the University of North Carolina at Chapel Hill. But with more resistance comes fewer second chances and less flexibility. That means we may have to use drugs that are harder to take or have more side effects. In rare but not unheard-of cases, people run out of options.
Fortunately, newer HIV medications are less likely to produce drug resistance mutations than older HIV medications.
Todays HIV treatments work, really well. Once common, HIV drug resistance has become a quite uncommon thing for patients taking modern medications, even among those with less than perfect adherence, Benjamin Young, MD, PhD, senior vice president and chief medical officer of the International Association of Providers in AIDS Care , told BETA.
In addition, some of the newer drugs today are particularly resistant to resistance.
Drug resistance is particularly uncommon among people taking first-line HIV integrase inhibitors. This appears to be especially true for dolutegravir , where only a single case of treatment-emergent resistance has been reported during initial treatment. With todays treatment options, dealing with drug resistant virus is easier, with potent and well-tolerated second-line options, said Young.
The Findings Revealed That Hiv Can Be Resistant To Many Different Drugs Simultaneously
Written by Agencies | Published : December 2, 2016 1:13 PM IST
Patients whose human immunodeficiency virus strains developed a resistance to older generation drugs are also resistant to modern drugs, a new study led by an Indian-origin scientist has found. Resistance to a drug typically occurs when patients doesn’t take their medication regularly enough, and for first-line treatments to work, patients generally need to take their medication 85-90 per cent of the time. The findings revealed that HIV can be resistant to many different drugs simultaneously. In the study, the researchers found that 16 per cent of people who stopped responding to modern first-line treatments had HIV mutations associated with resistance to an older generation of drugs called thymidine analogues. Among patients with a thymidine analogue mutation, 80 per cent were also resistant to tenofovir — the main drug in most modern HIV treatment and prevention strategies. We were very surprised to see that so many people were resistant to both drugs, as we didn’t think this was possible, said lead author Ravi Gupta, Professor at University College London.
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Hiv Replicates Quickly But Is Prone To Mistakes
If left untreated, HIV replicates prolifically, producing as many as 10 billion new viruses each day. But, at the same time, HIV is prone to coding errors when replicating. The viruses produced by these mistakes are called “mutations.”
“Mutation” does not inherently mean “resistant.” The vast majority of these are so distorted they are unable to infect or even survive.
However, on occasion, a mutation will emerge that is able to infect host cells and survive in the presence of antiretroviral drugs. These mutations are drug-resistant.
While they are less “fit” than wild-type viruses, their ability to escape the effects of the HIV treatment give them a better chance of not only surviving but predominating.
Ethics Approval And Consent To Participate
This project is not within the scope of the Belgian Law regarding research on human subjects of 7/5/2004 . This study did not involve patients and the interview did not contain personal questions, but rather involved questions about expert opinions on an international scientific problem, therefore, ethics approval was not required. Before the interviews began, all experts were informed about studys aim and methods and provided informed verbal consent for participation in the study. Participation was voluntary and the experts were free to terminate the interview at any time. Data was collected between October 2018 and February 2020. Face to face interviews were done in Italy and South Africa. We obtained a statement of a local ethical committee confirming that ethical approval in Italy was not necessary. We also refer to the Italian law of 5 June 2019 garante per la protezione dei dati personali. None of the four experts interviewed during a conference in South Africa, had the South African nationality. Ethical approval was not needed for this research as the South African Health Act of 2003 covers only research done on South African citizens. The interviewees were not study subjects but rather provided their professional opinion about a complex public health problem. Moreover, both the researcher who conducted the interviews and the principal investigator followed a South African good clinical practice course.
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Why Is Hiv Treatment Important
If taken as prescribed, HIV medicine reduces the amount of HIV in your blood to a very low level, which keeps your immune system working and prevents illness. This is called viral suppression, defined as having less than 200 copies of HIV per milliliter of blood.
HIV medicine can also make your viral load so low that a standard lab test cant detect it. This is called having an undetectable level viral load. Almost everyone who takes HIV medicine as prescribed can achieve an undetectable viral load, usually within 6 months after starting treatment. Many will bring their viral load to an undetectable level quickly, but it could take more time for a small portion of people just starting HIV medicine.
There are important health benefits to getting the viral load as low as possible. People with HIV who know their status, take HIV medicine as prescribed, and get and keep an undetectable viral load can live long and healthy lives.
There is also a major prevention benefit. People with HIV who take HIV medicine as prescribed and get and keep an undetectable viral load will not transmit HIV to their HIV-negative partners through sex. Learn more about the prevention benefits of having an undetectable viral load.
HIV treatment is most likely to be successful when you know what to expect and are committed to taking your medicines exactly as prescribed. Working with your health care provider to develop a treatment plan will help you learn more about HIV and manage it effectively.
When To Contact A Doctor
Schizophrenia causes a person to believe things that are not true or sense things that are not there. Consequently, it may be difficult for them to realize they have the condition or that it does not respond to treatment.
Aside from the typical schizophrenia symptoms, such as delusions and hallucinations, some signs that treatment may not be working include:
- A person feels anxious or upset about things others do not believe or see.
- Friends or loved ones continue to express concern about a persons emotions or behavior.
- A person feels that their life has not improved with medication.
- An individual feels like they think or live very differently from others.
Additionally, a person may benefit from extra support if:
- the side effects of medications are intense or feel intolerable
- they have difficulties remembering to take their medication
- they feel that treatment has stopped working
Managing treatment-resistant schizophrenia is difficult, and a person may continue to experience issues with treatment. A 2022 study of 63 people with treatment-resistant schizophrenia found that 25% responded to clozapine, the first-line treatment.
Certain factors correlated with a higher likelihood of treatment response, including:
- better social functioning in childhood and adolescence before diagnosis
- having the paranoid subtype of schizophrenia
- not waiting longer than 7 years to try clozapine
- trying at least one atypical antipsychotic schizophrenia drug
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