SIDE EFFECTS ARVLike most medicines, antiretroviral drugs can cause side effects. These unwanted effects are often mild, but sometimes they are more serious and can have a major impact on health or quality of life. On rare occasions, side effects can be life threatening.

Once started, antiretroviral treatment must be taken every day for life. Every missed dose increases the risk that the drugs will stop working. It is therefore vital that people receiving antiretroviral treatment get all the help they need to minimise the impact of side effects. Often there are several ways to lessen the harm, either byOther side effectsAbacavir hypersensitivity reactionVariation in side effectsAntiretroviral drugs differ in how commonly they cause particular side effects. For example, efavirenz is the drug most associated with psychiatric symptoms, while protease inhibitors are more likely to raise levels of cholesterol and triglycerides. This should be considered when deciding which drugs to take.

Side effects vary from person to person and it is impossible to predict exactly how each individual will be affected. Some people take antiretroviral treatment for years with few problems, while others find the same drugs intolerable. Nevertheless some characteristics and pre-existing conditions (such as high blood pressure or hepatitis infection) are known to increase the risk from certain side effects. Doctors should assess these factors before advising patients on which drugs to choose.

Duration of side effectsSome side effects appear shortly after starting an antiretroviral drug and disappear within a few weeks as the body gets used to the new chemicals. This is often the case with nausea, diarrhoea and headache, for example.

Unfortunately other side effects such as peripheral neuropathy (nerve damage) and lipodystrophy (fat redistribution) tend to worsen over time and may never go away. Also some problems may not emerge until months or even years after treatment is started.

Preparing to start treatmentThose preparing to take antiretroviral treatment for the first time, or about to switch drugs, are well advised to learn a little about the most commonly associated side effects. This should help them deal with problems as soon as they arise.

Patients should also know how to spot the warning signs of more serious side effects that may require immediate intervention.Reporting side effectsBecause side effects are unpredictable, may occur at any time, and can be very serious, it is essential that all symptoms be reported during appointments with a doctor. Severe or unexpected events should be reported immediately.

Keeping a side effects diary is a good way to keep track of when symptoms occur, how often and how severely. If side effects are affecting quality of life or treatment adherence then this too should be reported.

Identifying the causeMost side effects are not uniquely associated with a particular drug, and sometimes it can be difficult to identify the cause. HIV itself is capable of producing many of the symptoms that also occur as drug side effects. Other possible causes include opportunistic infections, stress, diet, and non-HIV drugs.

Patients should make sure their doctors are aware of all drugs they are taking. This means not only pharmaceuticals but also recreational drugs and complementary and alternative therapies. It may be that a side effect is due to one of these other substances, either directly or because of an interaction with the antiretroviral medication. The more information is shared with a doctor, the better equipped they will be to help.

Older people living with HIV may experience signs of ageing that could resemble certain side effects. For example, when people get older they might be more susceptible to increased fat in the abdomen, which could look similar to the changes that are caused by lipodystrophy.

Dealing with side effects

There may be several options for dealing with a particular side effect:Wait for things to improve especially if in the first few weeks of treatment.Address other possible contributing factors, such as diet, smoking or exercise. Change how the drug is taken (e.g. time of day, dosage, with or without food)

Try treating the side effectChange one or more antiretroviral drugs

Switching drugs is often an effective way to reduce or eliminate a side effect when all other approaches have failed. If the viral load is undetectable then it is usually possible to switch only one drug without affecting treatment effectiveness or future treatment options. Otherwise, the entire combination may have to be changed.

Switching drugs is not without risks. As already mentioned, it can be difficult to identify the cause of a particular set of symptoms, and it may turn out that the rejected drug or drugs werent to blame after all. There is also a chance that the new medication may cause even worse side effects, perhaps forcing another switch. Changing drugs repeatedly will narrow future treatment options. It is important to weigh the possible risks and benefits before deciding on this course of action.

It is never a good idea to stop treatment without first consulting a doctor, as this may cause HIV to develop drug resistance.

Overview of antiretroviral drug side effectsSome of the side effects of antiretroviral drugs are described below, beginning with five of the most notable. This is not a complete list.

DiarrhoeaDiarrhoea is a common side effect of many antiretroviral drugs especially protease inhibitors. Other possible causes include HIV, other infections and antibiotics. Sometimes an antiretroviral drug causes diarrhoea for only the first few weeks; in other cases this side effect lasts for as long as the drug is taken.The severity of diarrhoea also varies. While even occasional attacks may be inconvenient and embarrassing, persistent diarrhoea can also lead to dehydration, poor absorption of nutrients and drugs, weight loss and fatigue.

Drinking plenty of fluids and replacing electrolytes will reduce the risk of dehydration. Electrolytes such as potassium, sodium and magnesium ions are essential to health and are depleted by diarrhoea. Ways of replacing electrolytes include oral rehydration salts (available from pharmacies), sports rehydration drinks (such as Gatorade or Powerade, though the high sugar may worsen diarrhoea), diluted fruit juices, soups, and homemade rehydration mixtures (8 level teaspoons of sugar and 1 level teaspoon of table salt per litre of water). Eating bananas, potatoes, fish or chicken will help to replace potassium.

Although it may not be enough to solve the problem, changing diet may reduce the severity of diarrhoea. Good advice includes:1. Eat less insoluble fibre (raw vegetables, fruit skins, wholegrain bread or cereal, seeds and nuts)2. Eat more soluble fibre (white rice, pasta, oat bran tablets, psyllium/isphagula)3. Cut down on caffeine, alcohol and the sweetener sorbitol.

4. Avoid greasy, fatty, spicy and sugary foods5. Consider reducing dairy products in case of lactose intolerance6. Consult a dietician

Over-the-counter medicines such as Imodium (loperamide), Lomotil (diphenoxylate and atropine) and calcium supplements are sometimes all that is needed to control diarrhoea. If these fail then doctors can prescribe stronger treatments, which may have to be injected. Sometimes nothing works, and changing drugs may be the best option.Nausea and vomitingAlmost all antiretroviral drugs, as well as many other medications, can cause nausea (feeling sick) and vomiting, especially during the first few weeks of treatment. Although this side effect can reduce appetite, it is important to keep eating when possible, and to replace lost fluids and electrolytes (as with diarrhoea). The following measures may help:1. Eat several small meals instead of a few large meals2. Avoid spicy, greasy and rich foods; choose bland foods.

3. Eat cold rather than hot meals.

4. Dont drink with a meal or soon after.

5. Avoid alcohol, aspirin and smoking.

6. Avoid cooking smells

Some antiretroviral drugs can be taken with food, and doing so may lessen their harmful effects. It may also be possible to alter drug dosage or frequency.

Various treatments, known as anti-emetics, are available for nausea and vomiting, some of which do not require a prescription. There is some evidence that ginger and peppermint may help against nausea.

If nausea and vomiting are severe, or occur with other symptoms such as dizziness, thirst, fever, muscle pain, diarrhoea, headache or jaundice, then this may indicate a more serious problem such as lactic acidiosis or pancreatitis. In this case medical attention should be sought as soon as possible.

RashRashes often appear as a side effect of antiretroviral treatment. These may be itchy but are usually harmless and short-lived. However, severe rashes can occur with nevirapine, and more rarely with some other drugs. Any rash occurring during the first few weeks of treatment should be reported to a doctor immediately, as should any rash accompanied by fever, blistering, facial swelling or aches. A rash occurring with abacavir may indicate a very dangerous hypersensitivity reaction, as described later in this page.

Tips for coping with rashes include:1. Avoiding hot showers or baths.

2. Using milder toiletries and laundry detergents.

3. Wearing cool fibres such as cotton, and avoiding wool.

4. Humidifying the air.

5. Trying moisturisers/emollients or calamine lotion

Antihistamine tablets can sooth rashes and are generally available without a prescription. However, because these may interact with antiretroviral medications, patients should check with their doctors before using them. More severe skin problems may be treated with steroids.LipodystrophyLipodystrophy involves losing or gaining body fat, often in ways that can be disfiguring and stigmatising. Three main patterns are seen:1. Losing fat on the face, arms, legs and buttocks, resulting in sunken cheeks, prominent veins on the limbs, and shrunken buttocks.2. Gaining fat deep within the abdomen, between the shoulder blades, or on the breasts.3. A mixture of fat gain and fat loss.

Although lipodystrophy sometimes affects people with HIV who have not taken any antiretroviral drugs, it occurs more often among those receiving treatment. The condition is among the most common long-term side effects of combinations of drugs from the NRTI and protease inhibitor classes. It is particularly associated with stavudine, and to a lesser extent zidovudine. The precise causes of lipodystrophy remain unknown.

The treatments for lipodystrophy are sadly limited. Changing diet seems to make no significant difference, though resistance exercise (such as weight lifting) may improve the appearance of limbs by building muscle to compensate for lost fat. Any form of exercise will burn fat, which may make some parts of the body look better and others worse, depending on how fat has been redistributed. Aerobic exercise (such as running or swimming) tends to have more effect on the fat just below the skin than on the deep fat gained through lipodystrophy.

Doctors have tried using various medications, including human growth hormone, to treat lipodystrophy, but few have proved effective, and most have significant side effects. For people who have lost fat from the face, one option is injections of polylactic acid. This chemical (also known as New Fill or Sculptra) improves facial appearance by thickening the skin.

Switching antiretroviral treatment should stop the symptoms getting worse, but is unlikely to lead to much improvement once the condition has advanced.

Lipid abnormalities and the heartLipid abnormalities are another common side effect of some antiretroviral drugs particularly protease inhibitors and are often seen in people who also have lipodystrophy. Lipids are molecules of fat, cholesterol and related chemicals that have important roles in the body. Many factors including diet, smoking and exercise can affect the balance of these chemicals in the blood. Abnormal lipid levels can be harmful to health.

HIV positive people taking antiretroviral treatment commonly have high levels of a lipid called LDL cholesterol, low levels of HDL cholesterol, and high levels of triglyceride in the blood. Among HIV negative people such lipid abnormalities have been linked to greater risks of heart disease, stroke and diabetes.The first steps in treating lipid abnormalities should be related to diet and lifestyle. General recommendations include giving up smoking, taking more exercise, cutting calories, eating less fat, and consuming more fibre and omega-3 fatty acids (found in oily fish and flaxseed). However, people living with HIV should seek expert advice on applying these guidelines. For example, cutting calories may jeopardise attempts to build muscle, while eating less fat is not necessarily a good idea for people taking certain protease inhibitors that require fatty foods to aid absorption.

Yet although diet and lifestyle changes should always be part of the strategy, they are often inadequate to correct the problem. Doctors may prescribe medications such as statins and fibrates to improve lipid levels, or they may advise switching treatment.

September 24th, 2009 Posted by purwa | Uncategorized | no comments

Previous | Next HIV Related opportunistic infection : prevention and treatmentWhat are opportunistic infections?

People with advanced HIV infection are vulnerable to infections and malignancies that are called opportunistic infections because they take advantage of the opportunity offered by a weakened immune system.

A partial list of the worlds most common HIV-related opportunistic infections and diseases includes: Bacterial diseases such as tuberculosis, MAC, bacterial pneumonia and septicaemia (blood poisoning) Protozoal diseases such as toxoplasmosis, microsporidiosis, cryptosporidiosis, isopsoriasis and leishmaniasis Fungal diseases such as PCP, candidiasis, cryptococcosis and penicilliosis Viral diseases such as those caused by cytomegalovirus, herpes simplex and herpes zoster virus HIV-associated malignancies such as Kaposis sarcoma, lymphoma and squamous cell carcinoma.

Different conditions typically occur at different stages of HIV infection. In early HIV disease people can develop tuberculosis, malaria, bacterial pneumonia, herpes zoster, staphylococcal skin infections and septicaemia. These are diseases that people with normal immune systems can also get, but with HIV they occur at a much higher rate. It also takes longer for a person with HIV to recover than it takes for someone with a healthy immune system.

When the immune system is very weak due to advanced HIV disease or AIDS, opportunistic infections such as PCP, toxoplasmosis and cryptococcosis develop. Some infections can spread to a number of different organs, which is known as disseminated or systemic disease. Many of the opportunistic infections that occur at this late stage can be fatal.Why is there still a need to prevent and treat opportunistic infections?

Highly Active Antiretroviral Therapy (HAART) can reduce the amount of HIV in someones body and restore their immune system. The introduction of HAART has dramatically reduced the incidence of opportunistic infections among HIV-positive people who have received the drugs. Yet the prevention and treatment of opportunistic infections remains essential.

Around the world, millions of people living with HIV in resource-poor communities have no access to HAART. And even where the drugs are available, they do not entirely remove the need for preventing and treating opportunistic infections. Sometimes it is advisable for people with acute opportunistic infections to begin HAART right away, especially if the infection is difficult to treat. However in certain cases it may be better to delay beginning HAART and instead only to administer treatment for the opportunistic infection, especially if there are concerns about drug interactions or overlapping drug toxicities.

Those who have already started taking antiretrovirals may require other drugs in certain circumstances. In particular, some opportunistic infections may be unmasked shortly after the beginning of HAART as the immune system starts to recover, and these may require specific treatment. Measures to prevent and treat opportunistic infections become essential if antiretrovirals stop working because of poor adherence, drug resistance or other factors.

Providing prevention and treatment of opportunistic infections not only helps HIV-positive people to live longer, healthier lives, but can also help prevent TB and other transmissible opportunistic infections from spreading to others.Prevention of HIV-related opportunistic infections

HIV-positive people can reduce their exposure to some of the germs that threaten their health. They should be especially careful around uncooked meat, domestic animals, human excrement and lake or river water. However there is no practical way to reduce exposure to the germs that cause candidiasis, MAC, bacterial pneumonia and other diseases because they are generally common in the environment.

Several HIV-related infections (including tuberculosis, bacterial pneumonia, malaria, septicaemia and PCP) can be prevented using drugs. This is known as drug prophylaxis. One particular drug called cotrimoxazole (also known as septra, bactrim and TMP-SMX) is effective at preventing a number of opportunistic infections. This drug is both cheap and widely available. The World Health Organisation (WHO) recommends that, in resource-limited settings, the following groups of people should begin taking cotrimoxazole:

HIV-exposed infants and children, starting at 4-6 weeks after birth or at first contact with health care, and continued until HIV infection is excluded

HIV-positive children less than 1 year old

HIV-positive children aged 1-4 years who have mild, advanced or severe symptoms of HIV disease, or a CD4 count below 25%

HIV-positive adults and adolescents who have mild, advanced or severe symptoms of HIV disease, or a CD4 count below 350 cells per ml

HIV-positive people with a history of treated PCP.

According to WHO guidelines, treatment of HIV-positive children should continue until at least age five. In general treatment of adults and children should continue indefinitely, though it may sometimes be stopped following successful antiretroviral treatment.

Some of the worst affected countries may choose to treat all infants and children born to mothers confirmed or suspected of living with HIV, until HIV infection is excluded. They may also choose to treat everyone who is diagnosed with HIV, regardless of symptoms or CD4 count.

Drug prophylaxis is sometimes recommended even for those who have started HAART if they have very weak immune systems or are otherwise considered to be especially vulnerable. They may be advised to stop taking the drugs if their immune system recovers.

For people who have already contracted an opportunistic infection and undergone successful treatment, secondary prophylaxis may be advisable to prevent recurrence. This applies to diseases such as tuberculosis, salmonella, cryptococcosis and PCP.Treatment of HIV-related opportunistic infections

Some opportunistic infections are easier to treat than others. Effective treatment depends on health services being able to procure, store, select and administer the necessary drugs and to provide related treatment, care and diagnostic services to monitor health status and treatment response.

A few opportunistic infections and symptoms such as candidiasis of the mouth, throat or vagina (thrush), herpes zoster (shingles) and herpes simplex can be managed effectively through home-based care. In a home-based care setting diagnosis is made by observing symptoms.

Some opportunistic infections may be diagnosed by observation or using a microscope, and treated where there is minimal health infrastructure. Such infections include pulmonary tuberculosis and cryptococcal meningitis.

In a medium infrastructure setting, the facilities available include X-ray equipment and culture facilities. Using these, opportunistic infections such as extra-pulmonary tuberculosis, cryptosporidiosis, isopsoriasis, PCP and Kaposis sarcoma can be diagnosed and treated.

Opportunistic infections such as toxoplasmosis, MAC and cytomegalovirus infection can be diagnosed and treated in places with advanced infrastructure. Treating these infections is often impossible in resource poor countries. Many developing countries lack the advanced equipment and infrastructure (such as CT scanning) needed to treat these more complex infections.

Individual opportunistic infections

The following are just a few of the conditions that particularly affect people living with HIV.

Bacterial pneumoniaPneumonia can be caused by various bacteria. Symptoms among HIV-positive people are much the same as in those without HIV infection, and include chills, rigours, chest pain and pus in the sputum. The vaccine PPV can protect people against some of the more common pneumonia-causing bacteria, and is recommended in the US.

Because other forms of respiratory infection including PCP are common among HIV-infected people, doctors must be certain of diagnosis before administering antibiotics. This may require a chest radiograph, blood cultures, a white blood cell count and tests to eliminate other infections. Treatment is usually aimed at the most commonly identified disease-causing bacteria.

CandidiasisThere are two main types of candidiasis: localised disease (of the mouth and throat or of the vagina) and systemic disease (of the oesophagus, and disseminated disease). The mouth and throat variant (commonly known as thrush or OPC) is believed to occur at least once in the lifetime of all HIV-infected patients. Occurence of the vaginal variant is common among healthy women and is unrelated to HIV status.

While OPC is not a cause of death, it can cause oral pain and make swallowing difficult. The main symptom is creamy white legions in the mouth that can be scraped away. Oesophageal (gullet) candidiasis is a more serious condition which can cause pain in the chest that increases with swallowing. Disseminated candidiasis causes fever and symptoms in the organs affected by the disease (for example, blindness when it affects the eyes), and can be life threatening.

Localised disease may be treated at first with relatively inexpensive drugs such as nystatin, miconazole or clotrimazole. Systemic candidiasis requires treatment with systemic antifungal agents such as fluconazole, ketoconazole, itraconazole or amphotericin.

CryptococcosisCryptococcosis is caused by a fungus that primarily infects the brain. It most often appears as meningitis and occasionally as pulmonary or disseminated disease. Untreated cryptococcal meningitis is fatal.

Cryptococcosis is relatively easy to diagnose. However, its treatment (either amphotericin B with or without flucytosine or in mild cases with oral fluconazole) and secondary chemoprophylaxis are often impossible in developing countries because of high cost and limited availability of the drugs required.

Cryptosporidiosis and isosporiasisCryptosporidiosis (crypto) and isosporiasis are both caused by protozoan parasites. These diseases are easily spread by contaminated food or water, or by direct contact with an infected person or animal. Both crypto and isosporiasis cause diarrhoea, nausea, vomiting and stomach cramps. In people with healthy immune systems, these symptoms do not last more than about a week. However, if the immune system is damaged then they can continue for a long time. Diarrhoea can interfere with the absorption of nutrients and this can lead to serious weight loss.

To confirm diagnosis of either disease, the stool is normally checked for parasites and their eggs. There is no cure for crypto, but antiretroviral therapy to restore immunity can effectively clear up the infection. For isosporiasis, TMP-SMX (trimethoprim-sulfamethoxazole) is often the preferred treatment.

CytomegalovirusCytomegalovirus (CMV) is a virus that infects the whole body. It most commonly appears as retinitis, which causes blurred vision and can lead to blindness. CMV can also affect other organs, and is capable of causing fever, diarrhoea, nausea, pneumonia-like symptoms and dementia.

CMV infection may be treated with drugs such as ganciclovir, valganciclovir and forscarnet.

Herpes simplex and Herpes zosterThe usual symptoms of herpes simplex virus infection (HSV, which causes sores around the mouth and genitals) and herpes zoster virus infection (zonal herpes or shingles) are not life-threatening but can be extremely painful. Both viruses are also capable of causing retinitis and encephalitis (which can be life-threatening).

Both herpes simplex and herpes zoster are usually diagnosed by simple examination of the affected area, and may be treated with drugs such as acyclovir, famciclovir and valacyclovir.

Histoplasmosis is a fungal infection that primarily affects the lungs but may also affect other organs. Symptoms can include fever, fatigue, weight loss and difficulty in breathing.

Disseminated histoplasmosis infection may be diagnosed using an antigen test, and can be fatal if left untreated. Treatment usually involves amphotericin B or itraconazole.

Kaposis sarcomaHIV-associated Kaposis sarcoma causes dark blue lesions, which can occur in a variety of locations including the skin, mucous membranes, gastrointestinal tract, lungs or lymph nodes. The lesions usually appear early in the course of HIV infection.

Treatment depends on the lesions symptoms and location. For local lesions, injection therapy with vinblastine has been used with some success. Radiotherapy can also be used, especially in hard-to reach sites such as the inner mouth, eyes, face and soles of the feet. For severe widespread disease, systemic chemotherapy is the preferred treatment.

LeishmaniasisLeishmaniasis is transmitted by sandflies and possibly through sharing needles. The most serious of its four forms is visceral leishmaniasis (also know as kala azar) which is characterised by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver and anaemia (occasionaly serious). In its more common forms, leishmaniasis can produce disfiguring lesions around the nose, mouth and throat, or skin ulcers leading to permanent scarring.

Treatment of leishmaniasis with pentavalent antimony is relatively expensive, partly because of the cost of drugs but also because hospital admission is recommended (in milder cases, trained health workers may administer the injections or infusions at a patients home). If left untreated, visceral leishmaniasis is usually fatal.

MACThe germs of the mycobacterium avium complex (MAC) are related to the germ that causes tuberculosis. MAC disease generally affects multiple organs, and symptoms include fever, night sweats, weight loss, fatigue, diarrhoea and abdominal pain.

MAC should be treated using at least two antimycobacterial drugs to prevent or delay the emergence of resistance. Such drugs include clarithromycin, azithromycin, ethambutol and rifabutin.

PCPPCP is caused by a fungus, which was formerly called pneumocystis carinii but has now been renamed pneumocystis jirovecii. PCP is a frequent HIV associated opportunistic infection in industrialised countries but appears to be less common in Africa. The symptoms are mainly pneumonia along with fever and respiratory symptoms such as dry cough, chest pain and dyspnoea (difficulty in breathing). Definitive diagnosis requires microscopy of bodily tissues or fluids.

Severe cases of PCP are initially treated with TMP-SMX or clindamycin and oral primaquine. Mild cases can be treated with oral TMP-SMX throughout. With both of these regimens, toxicity (notably allergic-type reactions) often requires changes in therapy.

Prevention of PCP is strongly recommended for HIV-infected persons with very weak immune systems wherever PCP is a significant health problem for HIV-infected persons, and also after their first episode of PCP. The preferred drug is usually TMP-SMX.

ToxoplasmosisToxoplasmosis (toxo) is caused by a protozoan found in uncooked meat and cat faeces. This microbe infects the brain and can cause headache, confusion, motor weakness and fever. In the absence of treatment, disease progression results in seizures, stupour and coma. Disseminated toxo is less common, but can affect the eyes and cause pneumonia.

Definitive diagnosis of toxo requires radiographic testing (usually a CT or MRI scan). The infection is treated with drugs such as pyrimethamine, sulfadiazine and clindamycin. Leucovorin may also be used to prevent the side-effects of pyrimethamine.

TuberculosisTuberculosis (TB) is a bacterial infection that primarily infects the lungs. Tuberculosis is the leading HIV-associated opportunistic disease in developing countries. For people who are dually infected with HIV and TB, the risk of developing active tuberculosis is 30-50 fold higher than for people infected with TB alone. And because mycobacterium can spread through the air, the increase in active TB cases among dually infected people means:

more transmission of the TB germ

more TB carriers

more TB in the whole population.

Tuberculosis is harder to diagnose in HIV-positive people than in those who are uninfected. The diagnosis of TB is important because TB progresses faster in HIV-infected people. Also, TB in HIV-positive people is more likely to be fatal if undiagnosed or left untreated. TB occurs earlier in the course of HIV infection than many other opportunistic infections.

A proper combination of anti-TB drugs achieves both prevention and cure. Effective treatment quickly makes the individual non-contagious, which prevents further spread of the TB germ. The DOTS (directly observed short course) treatment strategy recommended by WHO treats TB in HIV-infected persons as effectively as it treats those without the virus. A complete cure takes 6 to 8 months and uses a combination of antibiotics. In addition to curing the individual, it also prevents further spread of the disease to others. This is why treating infectious cases of TB has important benefits for society as a whole.

Isoniazid preventive therapy is recommended as a health-preserving measure for HIV-infected persons at risk of TB, as well as for those with latent TB infection.

September 29th, 2009 Posted by purwa | Uncategorized | no comments

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