Methods of nonspecific and specific diagnosis of HIV infection. Terms of pretest counseling and testing for HIV. Post-test counseling. Psychological bases of communication with such patients. Principles and approaches to treatment for HIV infection. General characteristics of medicines groups used in treatment of HIV infection. General and specific prevention of HIV infection. Universal precautions and organization of medical prevention of HIV infection among medical personal. Safety during invasive manipulation. Measures in case of contamination by infectious material in the workplace
AQUIRED IMMUNODEFICIENCY SYNDROME
http://www.medicinenet.com/acquired_immunodeficiency_syndrome_aids/article.htm
AIDS stands for acquired immune deficiency syndrome and is the final stage of the infection caused by the virus called HIV or Human Immunodeficiency Virus. The virus causes severe damage to the immune system.
A retrovirus, the Human Immunodeficiency Virus (HIV) was identified in 1983 as the pathogen responsible for the Acquired Immunodeficiency Syndrome (AIDS). AIDS is characterized by changes in the population of T-cell lymphocytes that play a key role in the immune defense system. In the infected individual, the virus causes a depletion of T-cells, called “T-helper cells”, which leaves these patients susceptible to opportunistic infections, and certain malignancies. Credit: CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus.
AIDS is the sixth leading cause of death among people aged 25 – 44 in the United States. This is an improvement since it was the number one killer in 1995.
At the end of 2010, an estimated 91,500 people in the UK were living with HIV. Of these, around 1 in 4 (22,000 in total) did not know they were infected.
The World Health Organization (WHO) estimates that around 34 million people in the world are living with HIV. The virus is particularly widespread in sub-Saharan African countries, such as South Africa, Zimbabwe and Mozambique.
Those at highest risk include injection drug users who share needles, babies born to mothers with HIV (especially if the mother had not received anti- HIV therapy during pregnancy), those engaging in unprotected vaginal or anal sex with HIV positive individuals, and those who received blood transfusions or clotting products between 1977 and 1985 (before screening for HIV became standard practice).
HIV infection may cause no symptoms for a decade or longer. At this stage carriers may transmit the infection to others unknowingly. If the infection is not detected and treated, the immune system gradually weakens and AIDS develops.
Acute HIV infection takes a few weeks to months to become a non-symptomatic HIV infection. Then it becomes early symptomatic HIV infection and later it progresses to AIDS.
With advancing HIV infection the blood shows higher viral load and CD4 T-cell count drops below 200 cells/mm3. CD4 cells are a type of T cell. T cells are cells of the immune system. They are also called “helper cells.”
There is a small group of patients who develop AIDS very slowly, or never at all. These patients are called nonprogressors, and many seem to have a genetic difference that prevents the virus from significantly damaging their immune system.
These are infections that normally do not affect an individual with a healthy immune system but AIDS patients are susceptible to these infections. These include viral infections like:
herpes zoster infection
cancers like Kaposi sarcoma, non-Hodgkin’s lymphoma
fungal infections like candidiasis
bacterial infections like tuberculosis
Other infections include Bacillary angiomatosis, Candida esophagitis, Pneumocystic jiroveci pneumonia, AIDS dementia, Cryptosporidium diarrhea, cryptococcal meningigits and Toxoplasma encephalitis.
Diagnosis
HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women. Additionally testing is recommended for all those at high risk, which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.
A generalized graph of the relationship between HIV copies (viral load) and CD4+ T cell counts over the average course of untreated HIV infection. CD4+ T Lymphocyte count (cells/mm³) HIV RNA copies per mL of plasma
HIV testing
Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.
Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population was aware of their HIV status. In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested which represented a significant increase compared to previous years.
Classifications of HIV infection
Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease, and the CDC classification system for HIV infection. The CDC’s classification system is more frequently adopted in developed countries. Since the WHO’s staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.
The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses the following categories:
· Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.
Stage I: HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater than 500 per microlitre (µl or cubic mm) of blood. May include generalized lymph node enlargement.
Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.
Stage III: Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl.
Stage IV or AIDS: severe symptoms which include toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi’s sarcoma. A CD4 count of less than 200/µl.
The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in three stages:
Stage 1: CD4 count ≥ 500 cells/µl and no AIDS defining conditions
Stage 2: CD4 count 200 to 500 cells/µl and no AIDS defining conditions
Stage 3: CD4 count ≤ 200 cells/µl or AIDS defining conditions
Unknown: if insufficient information is available to make any of the above classifications
For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.
Prevention
Sexual contact
Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term. When condoms are used consistently by a couple in which one person is infected, the rate of HIV infection is less than 1% per year. There is some evidence to suggest that female condoms may provide an equivalent level of protection. Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection rates by approximately 40% among African women. By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation.[84] Circumcision in Sub-Saharan Africa “reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months”. Based on these studies, the World Health Organization and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007. Whether it protects against male-to-female transmission is disputed[87][88] and whether it is of benefit in developed countries and among men who have sex with men is undetermined. Some experts fear that a lower perception of vulnerability among circumcised men may cause more sexual risk-taking behavior, thus negating its preventive effects.
Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence for a benefit from peer education is equally poor. Comprehensive sexual education provided at school may decrease high risk behavior. A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV. It is not known whether treating other sexually transmitted infections is effective in preventing HIV.
Pre-exposure
Treating people with HIV whose CD4 count ≥ 350cells/µL with antiretrovirals protects 96% of their partners from infection. This is about a 10 to 20 fold reduction in transmission risk. Pre-exposure prophylaxis (PrEP) with a daily dose of the medications tenofovir, with or without emtricitabine, is effective in a number of groups including men who have sex with men, couples where one is HIV positive, and young heterosexuals in Africa. It may also be effective in intravenous drug users with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years.
Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV. Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapy appear effective in decreasing this risk.
Post-exposure
A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis (PEP). The use of the single agent zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury. As of 2013, the prevention regime recommended in the United States consists of three medications—tenofovir, emtricitabine and raltegravir—as this may reduce the risk further.
PEP treatment is recommended after a sexual assault when the perpetrator is known to be HIV positive, but is controversial when their HIV status is unknown. The duration of treatment is usually four weeks and is frequently associated with adverse effects—where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%).
Mother-to-child
Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%. This primarily involves the use of a combination of antiviral medications during pregnancy and after birth in the infant and potentially includes bottle feeding rather than breastfeeding. If replacement feeding is acceptable, feasible, affordable, sustainable, and safe, mothers should avoid breastfeeding their infants; however exclusive breastfeeding is recommended during the first months of life if this is not the case. If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.
Vaccination
As of 2012 there is no effective vaccine for HIV or AIDS. A single trial of the vaccine RV 144 published in 2009 found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the research community of developing a truly effective vaccine. Further trials of the RV 144 vaccine are ongoing.
Management
There is currently no cure or effective HIV vaccine. Treatment consists of high active antiretroviral therapy (HAART) which slows progression of the disease and as of 2010 more than 6.6 million people were taking them in low and middle income countries. Treatment also includes preventive and active treatment of opportunistic infections.
Antiviral therapy
Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)
Current HAART options are combinations (or “cocktails”) consisting of at least three medications belonging to at least two types, or “classes,” of antiretroviral agents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include a protease inhibitors (PI) are used if the above regime loses effectiveness.
When to start antiretroviral therapy is subject to debate. The World Health Organization recommends antiretrovirals in all adolescents, adults and pregnant women with a CD4 count less than 500/µl with this being especially important in those with counts less than 350/µl or those with symptoms regardless of CD4 count. This is supported by the fact that beginning treatment at this level reduces the risk of death. The United States in addition recommends them for all HIV-infected people regardless of CD4 count or symptoms; however it makes this recommendation with less confidence for those with higher counts. While the WHO also recommends treatment in those who are co-infected with tuberculosis and those with chronic active hepatitis B. Once treatment is begun it is recommended that it is continued without breaks or “holidays”. Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria treatment is effective in more than 95% of people during the first year.
Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death. In the developing world treatment also improves physical and mental health. With treatment there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include poor access to medical care, inadequate social supports, mental illness and drug abuse. The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence. Even though cost is an important issue with some medications, 47% of those who needed them were taking them in low and middle income countries as of 2010 and the rate of adherence is similar in low-income and high-income countries.
Specific adverse events are related to the antiretroviral agent taken. Some relatively common adverse events include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus, especially with protease inhibitors. Other common symptoms include diarrhea, and an increased risk of cardiovascular disease. Newer recommended treatments are associated with fewer adverse effects. Certain medications may be associated with birth defects and therefore may be unsuitable for women hoping to have children.
Treatment recommendations for children are slightly different from those for adults. In the developing world, as of 2010, 23% of children who were ieed of treatment had access. Both the World Health Organization and the United States recommend treatment for all children less than twelve months of age. The United States recommends in those between one year and five years of age treatment in those with HIV RNA counts of greater than 100,000 copies/mL, and in those more than five years treatments when CD4 counts are less than 500/µl.
Opportunistic infections
Measures to prevent opportunistic infections are effective in many people with HIV/AIDS. In addition to improving current disease, treatment with antiretrovirals reduces the risk of developing additional opportunistic infections. Vaccination against hepatitis A and B is advised for all people at risk of HIV before they become infected; however it may also be given after infection. Trimethoprim/sulfamethoxazole prophylaxis between four and six weeks of age and ceasing breastfeeding in infants born to HIV positive mothers is recommended in resource limited settings. It is also recommended to prevent PCP when a person’s CD4 count is below 200 cells/uL and in those who have or have previously had PCP. People with substantial immunosuppression are also advised to receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis. Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.
Alternative medicine
In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. With respect to dietary advice and AIDS some evidence has shown a benefit from micronutrient supplements. Evidence for supplementation with selenium is mixed with some tentative evidence of benefit. There is some evidence that vitamin A supplementation in children reduces mortality and improves growth. In Africa in nutritionally compromised pregnant and lactating women a multivitamin supplementation has improved outcomes for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization. The WHO further states that several studies indicate that supplementation of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults. There is not enough evidence to support the use of herbal medicines.
Prognosis
HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the world. Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months. HAART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young adult to 20–50 years. This is between two thirds and nearly that of the general population. If treatment is started late in the infection, prognosis is not as good: for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years. Half of infants born with HIV die before two years of age without treatment.
The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are frequently the result of the progressive failure of the immune system. Risk of cancer appears to increase once the CD4 count is below 500/μL. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person’s susceptibility and immune function; their access to health care, the presence of co-infections; and the particular strain (or strains) of the virus involved.
Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS being present in a third of all HIV infected people and causing 25% of HIV related deaths. HIV is also one of the most important risk factors for tuberculosis. Hepatitis C is another very common co-infection where each disease increases the progression of the other. The two most common cancers associated with HIV/AIDS are Kaposi’s sarcoma and AIDS-related non-Hodgkin’s lymphoma.
Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders, osteoporosis, neuropathy, cancers, nephropathy, and cardiovascular disease. It is not clear whether these conditions result from the HIV infection itself or are adverse effects of treatment.
Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants as of 2004.
|
no data ≤ 10 10–25 25–50 50–100 100–500 500–1000 |
1000–2500 2500–5000 5000–7500 7500-10000 10000-50000 ≥ 50000 |
Religion and AIDS
The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because some religious authorities have publicly declared their opposition to the use of condoms. The religious approach to prevent the spread of AIDS according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global AIDS Crisis argues that cultural changes are needed including a re-emphasis on fidelity within marriage and sexual abstinence outside of it.
Some religious organisations have claimed that prayer can cure HIV/AIDS. In 2011, the BBC reported that some churches in London were claiming that prayer would cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV reported that several people stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of deaths. The Synagogue Church Of All Nations advertise an “anointing water” to promote God’s healing, although the group deny advising people to stop taking medication.
Media portrayal
One of the first high-profile cases of AIDS was the American Rock Hudson, a gay actor who had been married and divorced earlier in life, who died on 2 October 1985 having announced that he was suffering from the virus on 25 July that year. He had been diagnosed during 1984. A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony Eden
On November 24, 1991, the virus claimed the life of British rock star Freddie Mercury, lead singer of the band Queen, who died from an AIDS related illness having only revealed the diagnosis on the previous day. However he had been diagnosed as HIV positive during 1987. One of the first high-profile heterosexual cases of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992. He died, aged 49, as a result on 6 February 1993.
Therese Frare’s photograph of gay activist David Kirby, as he lay dying from AIDS while surrounded by family, was taken in April 1990. LIFE magazine said the photo became the one image “most powerfully identified with the HIV/AIDS epidemic.” The photo was displayed in LIFE magazine, was the winner of the World Press Photo, and acquired worldwide notoriety after being used in a United Colors of Benetton advertising campaign in 1992. In 1996, Johnson Aziga a Ugandan-born Canadian was diagnosed with HIV, but subsequently had unprotected sex with 11 women without disclosing his diagnosis. By 2003 seven had contracted HIV, and two died from complications related to AIDS. Aziga was convicted of first-degree murder and is liable to a life sentence.
Denial, conspiracies, and misconceptions
A small group of individuals continue to dispute the connection between HIV and AIDS, the existence of HIV itself, or the validity of HIV testing and treatment methods. These claims, known as AIDS denialism, have been examined and rejected by the scientific community. However, they have had a significant political impact, particularly in South Africa, where the government’s official embrace of AIDS denialism (1999–2005) was responsible for its ineffective response to that country’s AIDS epidemic, and has been blamed for hundreds of thousands of avoidable deaths and HIV infections. Operation INFEKTION was a worldwide Soviet active measures operation to spread information that the United States had created HIV/AIDS. Surveys show that a significant number of people believed – and continue to believe – in such claims.
There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS, and that HIV can infect only homosexual men and drug users. Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.
Clinical manifestations
http://www.ucsfhealth.org/conditions/aids/signs_and_symptoms.html
The time from exposure to HIV until the onset of the acute clinical illness is typically 2 to 4 weeks, although longer incubation period have been reported. The clinical illness is acute in onset and lasts from 1 to 2 weeks. It can be associated with an appreciable degree of morbidity and patient may require hospitalization. The main clinical features of primary HIV infection reflected both the lymphocytopatic and neurologic tropism of HIV. Patients report fever, lethargy, fatigue, headaches, retro-orbital pain, sore throat, muscular pain, occasional diarrhea, maculopustular rash and the onset of swollen lymph nodes (swollen glands). Meningoencephalitis may also occur. Lethargy and malaise are frequent, often severe and may persist for several months after resolution of the other clinical manifestations of primary HIV infection. Lymphoadenopathy develops in approximately 70 % of persons, generally in the second week of the illness and usually concomitant with the development of peripheral lymphocytosis, reflects the fact that HIV has activated B-lymphocytes to become plasma cells and secrete HIV antibodies.
AIDS lymphoadenopathy
The lymphoadenopathy may be generalized, but the occipital, axillary and cervical nodes are most commonly involved. The lymph node enlargement persist after the acute illness bat tend to decrease with time. Splenomegaly has also been reported. The mechanism for this splenomegaly is not apparent; it may be related to increased clearance of virally infected lymphocytes. The most frequently reported dermatologic evidence of primary. HIV infection is an erythematous, nonpruritic maculopapular rash. This rash is generally simmetric, with lesions 5 to 10 mm in diameter, and affects the face or trunk, but it can also affect the extremities including the palms and soles, or can be generalized. Other skin lesions noted during primary HIV infection include a roseola-like rash, diffuse urticaria, vesicular, pustular exanthema and enanthema, desquamation of the palms and soles and alopecia. Mucocutaneous ulceration is a distinctive feature of primary HIV infection. Ulcer have been reported on the buceal mucosa, gingiva, or palate, esophagus, anus, and penis. They are generally round or oval and sharply demarcated, with surrounding mucosa that appears normal. The tongue of patient showing the characteristic symptoms of thrush. Note the milk-white flakes of C. albicans on the tongue surface. An unexplained incident of thrush is often considered an early sign that HIV infection is present. Patients also experience weight loss of as much as 10 % of baseline body weight or more. Constant low-grade fever and diarrhea extending over several weeks. In addition, the fatigue may be so overwhelming that patients cannot lift their heads from the pillow on waking in the morning. One of the most troublesome aspects is the night sweats. Individuals perspire so heavily at night that the bed linens and nightwear become drenched with sweat. Saturation can be extensive enough to require linen changes, and sleep is fitful at best. Few other microbial diseases are accompanied by such heavy sweating.
The isolation of HIV from cerebrospinal fluid (CSF) during primary HIV infection indicates that infection of the central nervous system (CNS) occurs soon after exposure. Elevated neopterin and β2-microglobulin levels have also been found in CSF during primary HIV infection both in individuals with and without clinical meningitis, suggesting that the cellular immune system in the CNS may be activated during this stage even without the development of overt neurologic symptoms or signs. The most commoeurologic symptoms are headaches, retro-orbital pain (particularly during eye movement) and photophobia. Several cases of aseptic meningoencephalitis during primary HIV infection have been reported.
Prolonged infection with HIV is often completely asymptomatic; however, a minority of patients complain of nonspecific constitutional symptoms in the month or years after primary infection. Patients commonly complain of being easily fatigued and report the need to reduce their normal activities somewhat. In patients with more advanced HIV disease and severe de pletion of CD4 cells, constitutional disease may primarily reflect immunosupression or may herald the onset of opportunistic infections or malignancies. Patients with progressive constitutional symptoms should be evaluated carefully for opportunistic pathogens. A history of respiratory, neurologic, gastrointestinal and dermatological symptoms should be elicited and a thorough physical examination completed.
In the late stages of HIV infection when immune defenses have been severely compromised and systemic complications have begun to accumulate, the nervous system becomes highly susceptible to a wide array of disorders involving all levels of the neuraxis, including meninges, brain, spinal cord, peripheral nerve, and muscle.
Systemic lymphoma complicating HIV infection may secondarily to the central nervous system involving the meninges, clinical manifestation may be cryptic but usually include cranial nerve palsies, head aches, or increased intracranial pressure.
From an early stage it become clear that the nervous system was frequently involved in HIV infected patients. Among the severe and life-threatening infections experienced by those with immune deficiency were brain abscesses due to toxoplasmosis. As other neurologic manifestations emerged without signs of recognizable opportunistic infection it became clear that HIV was probably directly neurotropic as well as lymphotropic.
Toxoplasma gondii is an obligate intracellular parasite for which the primary host is the cat. Humans may acquire it from the cat by the fecal-oral route. in man primary infection is usually asymptomatic unless congenitally acquired. The organism forms cysts in all tissues which persist for life and are the source of recrudescent infection in the compromised host. Infection in the brain is usually multifocal as old encysted parasites become actively pathogenic again. The clinical presentation may be focal or diffuse but is a cerebrovascular accident, but is more usually progressive aver a few days or a week or two.
Peripheral neuropathies of several types can complicate the various stages of HIV infection. Early in the course of HIV infection a Guillain-Barre type of neuropathy may be seen. The clinical picture is the same as the familiar acute inflammatory or postinfectious neuropathy, with weakness of limb and facial muscles, minor sensory symptoms and loss of tendon reflexes. The weakness tends to be both proximal and distal. There bay be backache and limb pains. There is evidence that the axonal neuropathy in the late stages of the disease correlated with the presence of dementia. Its ethnology is unknown, but it has been suggested that it may be a direct effect of HIV.
The most prevalent opportunistic disease among persons with HIV in late stage is Pneumocystis carinii pneumonia. Recently, however, studies of ribosomal RNA of P. carinii have shown that phylogenetically the organism is most closely related to the Ascomycetes (yeasts): thus P. carinii should probably be considered a fungus rather than a parasite. This reclassification has little clinical relevance but may suggest new therapeutic approaches and culture techniques. P. carinii is thought to have a life cycle consisting of three stages: cyst, whish are spherical or crescent-shaped form 5 to 8 mm in diameter; sporozoites or intracystic bodies, found only within the cyst; and tropozoites, found outside the cyst and believed intermediate between the sporozoite and the cyst. The Giemsa stain is taken up by both the intracystic sporozoites and extracystic tropozoites; cyst are not pozitively stained and cannot be seen except as negative images within the matrix of a clump of tropozoites. Infection with P. carinii is common early in the life and dose not generally results in symptomatic disease in immunocompetent hosts. Until the occurrence of the epidemic of infection with the HIV P. carinii pneumonia was an uncommon, sporadic disorders that occurred primary in patient with leukemia or other recognized causes of impairment of host defences and in patients who were given immunosuppressive therapy. Several studies in the United States have shown that circulating antibodies to P. carinii develop in mot children by age 2 to 3 years, leading to the conclusion that asymtomatic infection with P. carinii is nearly universal at least in the areas where these studies were conducted. Patients with P. carinii pneumonia usually have had non-specific symptoms such as fever, fatigue, and weight loss for weeks to months before developing respiratory symptoms and often have other HIV-related disorders that indicate severe immunosupression. The most common presenting symptoms of P. carinii pneumonia are fever, non-productive cough, and progressive shortness of breath. IN patient with P. carinii pneumonia chest radiographs most often show diffuse interstitial infiltration involving all portion of the lungs. Several variations may be seen. The infiltration may be heterogenously distributed throughout the lung, or it may be miliary in appearance. Diffuse or local air-space consolidation may also be noted. In patients who are being given aerosol pentamidine prophylaxis, focal upper lobe infiltration are relatively common. Cystic changes or pneumatoceles may occur, especially during the healing process, and cavitation withing pre-existing nodular lesions has been described. Probably as a result of the cystic or cavitary processes, spontaneous pneumothorax may occur. Pleural effusion and intrathoracic adenopathy are very uncommon with P. carinii pneumonia.
Since the beginning of the HIV epidemic an increasing association of Mucobacterium tuberculosis infection with HIV infection has beeoted. Between 1978 and 1985 the yearly rate of tuberculosis more than doubled at one New York City hospital. Although the pathogenesis of most HIV associated tuberculosis appears to involve reactivation of latent M. tuberculosis infection, the clinical presentation is generally typical of reactivation tuberculosis only for those patients whose immune function is still relatively intact, whereas that of patients with HIV is much more typical of progressive primary tuberculosis. Only one-third to one halt of HIV-associated tuberculosis is confined to the lungs. The most frequent radiographic manifestations of pulmonary tuberculosis in patients with HIV are hilar or mediastinal adenopathy or both and localized infiltrates limited to the middle or lower lung fields. Pulmonary cavitation is rarely seen. The classic radiographic picture of apical infiltrates in the absence of hilar or mediastinal adenopathy has been reported in less than 10 % of HIV-associated cases. One half to two thirds of HIV-related tuberculosis involves extrapulmonary sites (with or withoutpulmonary involvement). Perioheral lymph nodes and bone marrow are the extrapulmonary biopsies but rarely in pulmonary biopsies. Other extrapulmonary sites that have revealed M. tuberculosis include urine, blood, bone, joint, cerebrospinal fluid, liver, spleen, skin, gastrointestinal mucosa and ascites fluid. Two extrapulmonary tuberculosis syndromes described in HIV patients are of particular interest: M. tuberculosis bacteremia and central nervous system mass lesions. On the other hand, tuberculosis in patients with otherwise asymptomatic HIV infection usually is clinically similar to tuberculosis in immunocompetent hosts.
The association of disseminated Mycobacterium avium complex (MAC) infection with HIV was recognized early in the HIV epidemic. Disseminated MAC infection has been reported only rarely in patients without HIV. Disseminated MAC infection occurs exclusively in patients with very advanced HIV disease essentially only in patients with CD4 lymphocyte counts<100/ml. MAC is a ubiquitous soil and water saprophyte. The source of MAC invasion in HIV patients may be gastrointestinal or respiratory. The presence of large clusters of mycobacterium within macrophagas of the small bowell lamina propria suggests the bowel wight be the portal of entry. However, respiratory isolation of the MAC also frequently precedes disseminated infection, suggesting MAC infection may begin in the lungs as well. Since most HIV patients with disseminated MAC infection have other concomitant infections or neaplasms and since MAC appears to cause little histopathologic evidence of inflammatory response or tissue destruction, the relationship between constitutional symptoms, organ dysfunction, and MAC infection has been uncertain.
Four clinical syndromes often over lapping, have been associated with disseminated MAC infection.
– Systemic symptoms. Fever, malaise, weight loss often associated with anemia, neutropenia.
– Gastrointestinal symptoms.
– Chronic diarrhoea and abdominal pain (MAC infection of colon often observed at autopsy)
– Chronic malabsorbtion (histopatologic changes in small intestine similar to those with Whipple’s disease often observed at autopsy)
– Extrabiliary obstructive jaundice secondary to periportal lymphadenopathy.
Cryptococcus neaformans and tuberculosis are the major opportunistic infection complicating the HIV epidemic world-wide. Although other pathogens may dominate on individual continents or in specific regions, no other major pathogen poses as great a global threat to those immunocompromised by HIV infection. The high mortality and morbidity rates associated with cryptococcal infection and the toxicity of traditional therapy have sparred intense interest iew treatment alternatives. A better understanding of the natural history of HIV-mediated immunodepression has seen the emergence of debate about the use and advisability of fungal prophylactic. This organism a common resident of the lung, is often inhaled from the air. It grows actively in the droppings of pigeons and enters the air in wind borne particles. The fungus is generally noninfectious, but in patients with HIV it multiplies in the lungs, spreads to the blood and localized on the brain and its coverings. The clinical presentation of cryptococcal disease in HIV patient is often subtle and nonspecific. A prolonged febrile prodrome, indistinguishable from that accompanying other opportunistic infections is common. Frequently no localizing signs or symptoms are present to guide the physician toward the diagnosis of cryptococcal disease. Although the portal of entry for C. neoformans is the lung. Pulmonary cryptococcosis is usually clinically. Most cases of pulmonary cryptococcal infection are discovered serendipitously, not because of organ specific signs or symptoms. Occasionally, however, pulmonary symptoms dominate the clinical presentation and progression to respiratory failure and death are not unknown. However, among those HIV-infected patients with cryptococcal disease and without CHS involvement, fully two thirds had cough and shortness of breath. In contrast only 18% of those patients with culture-proven CNS disease had respiratory symptoms. These numbers add weight to the argument that all patients with CNS involvement have or have had antecedent pulmonary infection. Blood-borne spread to any organ, but the organism has a predilection for the CNS. It causes a granulomatous meningitis with or without clinically evident pulmonary or disseminated infection. In addition, there may be small cysts in the cerebral cortex. The clinical presentation is usually with headache, fever, and constitutional upset; neck stiffness, photophobia and focal neurologic signs are present.
Skin disease is an extremely common complication of HIV infection, affecting up to 90% of persons. Some of the skin conditions also are commonly seen in uninfected persons (e.g. seborrheic dermatitis) but are of increased severity in the HIV infected person. Other skin diseases are relatively unique to HIV infection (Kaposi’s sarcoma).
Elements of Kaposi’s sarcoma
The average HIV infected patient has at least two and often more different skin conditions simultaneously. It is useful to classify the cutaneous disorder seen with HIV disease as either infectious disorder, hypersensitivity disorders and drug reactions, or neoplasms.
Oral lesions have been recognized as prominent features of HIV infection since the beginning of the epidemic. Some of these changes are reflections of reduced immune function manifested as oral opportunistic conditions, which are often the earliest clinical features of HIV infection. Some, in the presence of known HIV infection are highly predictive of the ultimate development of the full syndrome, whereas others represent the oral features of AIDS itself.
Oral lesions in AIDS
They include oral infections in patients with primary immunodeficiency, leukemia, and diabetes, and those resulting from radiation therapy, cancer chemotherapy and bone marrow supression. In the prospective cohorts of HIV infected homosexual and bisexual men hairy leukoplakia pseudomembranous candidiasis are the most common oral lesions.
Oral Kaposi’s sarcoma in AIDS
Kaposi’s sarcoma (KS) in patients with AIDS produces oral lesions in many cases.
The lesions occur as red or purple macules, papules, or nodules. Occasionally the lesions are the same color as the adjoining normal mucosa. Although frequently asymptomatic, pain may occur because of traumatic ulcerisation with inflammation and infection. Bulky lessions may be visible or may interfere with speech and mastication. Diagnosis involves biopsy. Lesions at the gingival margin frequently become inflamed and painful because of plaque accumulation.
From the outset of the HIV epidemic, clinicians everywhere noted a high prevalence of the gastrointestinal (GI) signs and symptoms. Some of these manifestation such as weight loss, dysphagia, anorexia, and diarrhoea are almost universally among patients with HIV. Early and complete invasive and noninvasive evulation of these patients should be undertaken with particular attention to treatable non-HIV-associated biliary tract disease. Hepatic parenchymal disease likewise is common in patient with HIV infection.
Cramping paraumbilical abdominal pain, weight loss and large-volume diarrhea are common in patient with HIV disease.
Loss of weight in AIDS
The majority of HIV patients with these complaints has specific small bowel infection. Certainly routine colonic bacterial pathogens such us Salmonella, Shigella and Campylobacter, which may be persistent and mimic chronic inflammatory bowel disease, should be excluded by the adequate culture techniques. Likewise, routine and atypical parasitic infestation including that caused by Giardia lamblia, E. histolytica, Criptosporidium and I. belli must be excluded. Colonic diarrhea usually is associated with frequent small volume stools, left lower quadrant or suprapubic cramping, rectal urgency (tenesmus), and proctalgia and dyskenesia (painful defecation). On occasion a small amount of bright red blood may be noted. Once again, in the majority of these patient with diarrhea of colonic origin, specific bacterial and parasitic pathogens can and should be easily isolated by careful analysis of the stool. In addition some patient may have classic herpetic perianal ulceration which can be diagnosed by specific viral culture of swabs taken directly from the perianal area. CMV proctocolitis has been described as having sigmoidoscopic features suggestive of focal ishemic colitis that is submucosal hemorrhages and discrete shallow ulceration of distal colonic mucosa. Once again, obtaining specific biopsy specimens for histology and viral culture is indicated. Even in the absence of focal or diffuse colonic mucosal changes, biopsy specimens should be taken for histologic evaluation to look for the occasional patient with Cryptosporidium whose stools have been negative for this organism.
On occasion, patients with HIV may suddenly develop ascites. Since some HIV-infected patient may have underlying cirrhosis (caused by either alcohol consumption or viral hepatitis), a sizeable percentage of them will have transudative ascites related to their chronic liver disease. Careful evaluation of the ascites fluid, including performing cytology, and acid-fast stains should be done early to exclude patients with malignancy and tuberculosis peritonitis.
Malignancies as a complication of immunodeficiency have been well described in the literature, being recognized long before the advent of the HIV epidemic. The incidence of both Kaposis sarcoma (KS) and non-Hodgkin’s lymphoma (NHL) are marked by increased in immunosuppressed allograft recipients. It is therefore not suprising that patients with HIV infection, who also have proformed defects in cell-mediated immunity also develop these two malignancies. KS once a rarely reported malignancy is the most commoeoplasm affecting HIV-infected individuals. IT is seen primarily in homosexual men and has only rarely been reported in intravenous drug users or other risk groups. The pathogenesis of KS and HIV-infected patients remain uncertain. The natural history of KS associated with HIV infection more closely resembles that observed in immunosuppressed allograft patients. The disease tends to progress with time and is associated with the appearance of larger and more numerous cutaneous lesions.
Cutaneous lesions in AIDS
However, the course of the disease is unpredictable. A patient may have relatively few lesions that remain stable over time. New cutaneous lesions may not appear for many months but may be followed by a sudden and rapid increase in disease activity. Visceral involvement with KS is extremely common and can involve almost any visceral site. Careful endoscopic examination will reveal gastrointestinal sites of disease in most patient. Athough KS is usually not a direct cause of death in HIV-infected, the morbidity associated with more advanced disease with more advanced disease can be significient.
Cutaneous lesions may become painful and if large cutaneous surfaces are involved can restrict movement. Lymphatic obstruction is common and can result in severe edema, most commonly involving the extremities or the face. visceral spread of KS is rarely symptomatic, particularly when it involves the gastrointestinal tract. Careful examination of the skin and oral cavity at each clinic visit is the key to early diagnosis. Once lesions are identified, histologic confirmation should be obtained.
The non Hodgkin’s lymphomas are a heterogenous group of malignancies. Their biologic behavior ranges from indolent requiring no therapy, to aggressive malignancies with few long-term survivors. In the most commonly used classification system for the NHL, these malignancies are divided into three major categories: low grade, intermediate grade, and high grade, according to pathologic characteristics of involved lymph nodes and morphologic criteria of the lymphoma cells.
Infection with the HIV is associated with a wide spectrum of hematologic abnormalities. These abnormalities are found in all stages of HIV disease and involve the bone marrow, cellular elements of the peripheral blood and coagulation pathways. The cause of these abnormalities is multifactorial. A direct suppressive effect of HIV infection, ineffective hematopoiesis, infiltrative disease of the bone marrow, nutritional deficiencies, peripheral consumption secondary to splenomegaly or immune dysregulation, and drug effect all contribute to the variety of hematologic findings in these patients. Many of these abnormalities are clinically significant, whereas others are more of academic interest.
Peripheral cytopenias are common in HIV-infected individuals and are due to either decreased production in the bone marrow or accelerated destruction in the peripheral circulation. In general the cytopenias increase in frequency as HIV-disease progresses. Anemia is the most common hematologic abnormality noted in patients with HIV disease. The largest HIV infection affects the lymphocyte, neutrophil and macrophage monocyte cell lines. Despite the hyperhammahlobulinemia noted in these patient, they suffer complications from both defective cellular immunity and dysregulated humoral immunity. The hallmark of HIV infection is progressive depletion of the CD-4 lymphocytes. This decrement presumably occurs through direct viral invasion of these cells. Early in HIV infection an initial increase in the CD-4 population occurs before a decline in the number of CD-4 cells is noted. Granulocytopenia independent of drug use is noted in approximately 50 % of patients with HIV. Drug-induced neuthropenia is in the HIV-infected individual. Medication used to treat infection such as P. carinii pneumonia, toxoplasmosis and cytomegalovirus retinitis or colitis cause neuthropenia. Similarly, ridovudine is implicated as a cause of neuthropenia, ofteecessitating dose reduction or cessation of therapy. As for the complication of neuthropenia, most documented infection involve gram-negative organisms. The most common platelet abnormality found in HIV-infected patients is thrombocytopenia have only minor submucosal bleeding. characterized by petechiae, echymoses and occasional epistaxis. Rare patients have gastrointestinal blood loss. Laboratory findings reveal that patients generally have isolated thrombocytopenia, which usually is not accompanied by anemia and leukopenia. Patients with HIV infection, including those being treated with antibodies for an AIDS-opportunistic infection and those being treated with cytotoxic chemotherapeutic agents for HIV-related malignancies, may also develop thrombocytopenia secondary to a therapeutic intervention. In these patients severe thrombocytopenia should be managed as it is in the non-HIV-infected individual. Medications causing thrombocytopenia should be discontinued and platelet transfusion should be administered when indicated.
Diagnostics
http://www.ucsfhealth.org/conditions/aids/diagnosis.html
The first test developed to detected HIV infection was isolation of the virus through tissue culture. Unfortunately although sensitive for viral isolation the tissue culture procedure is expensive, time consuming and labor intensive. As a result soon after the initial discovery of HIV several tests were developed using protein products of the newly discovered virus to detect antibodies produced by the infected host. The two antibodi tests used most commonly are the enzyme-linked immunosorbent assay (ELISA) and the western blot. In addition to being less expensive, faster and easier to perform than viral culture, the ELISA and the Western blot test do not require working with like virus and therefore are safer. Over the best some years several novel techniques have been developed. The radioimmunoprecipitation assay (RIPA) is a more time consuming, and labor intensive test the Western blot, yet it provides much finer resolution of the high-molecular-weight envelope proteins than the western blot test. The RIPA is considered more sensitive and specific than the Western blot test, however, the time, expense, and need for active cell lines and radioactive materials make the RIPA a poor choice for routine testing in commercial laboratories. Rather its use is best reserved for difficult-to-diagnose cases. Like the RIPA the indirect immunofluorescence assay (IFA) requires preparation of HIV antigens that are expressed on infected cells and are stained subsequently. Infected cells are placed on the glass slides in a fixed monolayer and are incubated with patient serum. Anti-HIV antibodies present within the serum bind to antigens expressed on the surface of cells, and these bound antibodies are then detected with anti-human antibody that has been labeled with fluorescein isothiocyanate an ultraviolet-activated dye compound. after appropriate processing, the slide is viewed under a fluorescent microscope and the number of cells the intensity of staining and the staining pattern are assessed. Polymerase chain reaction (PCR) technique, introduced in the late 1980s, represent a major advance in the diagnosis of many disorders, including HIV infection. This powerful technique can amplify DNA existing in very small quantities through a series of binary replicative cycles. The PCR procedure can also be applied to RNA.
The pool of human lymphocytes possesses specific glycoproteins of their surface that play an important role in the cells activity and function CD-4 positive lymphocytes are the primary target of HIV infection, and the CD-4 receptor is the primary binding site of HIV. Throughout the course of chronic HIV infection the number of CD-4 lymphocytes is depleted and the loss of these cells is associated with development of the characteristic opportunistic infection and malignancies of AIDS. Thus the measurement of CD-4 positive lymphocytes is one of the most impotent determinates for clinically staging the disease status of HIV infected patients. In uninfected controls normal values for the CD-4/CD-8 ratio are 2.0 to 1.0. Normal values for CD-4 counts are generally 500 to 1000 cells/ml3 in adults.
HIV is most commonly diagnosed by testing your blood or saliva for the presence of antibodies to the virus. Unfortunately, these types of HIV tests aren’t accurate immediately after infection because it takes time for your body to develop these antibodies — usually up to 12 weeks. In rare cases, it can take up to six months for an HIV antibody test to become positive.
A newer type of test checks for HIV antigen, a protein produced by the virus immediately after infection. This test can confirm a diagnosis within days of infection. An earlier diagnosis may prompt people to take extra precautions to prevent transmission of the virus to others. There is also increasing evidence that early treatment may be of benefit.
Tests to tailor treatment
If you receive a diagnosis of HIV/AIDS, several types of tests can help your doctor determine what stage of the disease you have. These tests include:
· CD4 count. CD4 cells are a type of white blood cell that’s specifically targeted and destroyed by HIV. A healthy person’s CD4 count can vary from 500 to more than 1,000. Even if a person has no symptoms, HIV infection progresses to AIDS when his or her CD4 count becomes less than 200.
· Viral load. This test measures the amount of virus in your blood. Studies have shown that people with higher viral loads generally fare more poorly than do those with a lower viral load.
· Drug resistance. This blood test determines whether the strain of HIV you have will be resistant to certain anti-HIV medications and the ones that may work better.
Tests for complications
Your doctor might also order lab tests to check for other infections or complications, including:
· Tuberculosis
· Hepatitis
· Toxoplasmosis
· Sexually transmitted infections
· Liver or kidney damage
· Urinary tract infection
Treatment
http://www.ucsfhealth.org/conditions/aids/treatment.html
Photo of a variety of different drug treatments.
In the early 1980s when the HIV/AIDS epidemic began, people with AIDS were not likely to live longer than a few years.
Today, there are 31 antiretroviral drugs (ARVs) approved by the Food and Drug Administration to treat HIV infection. These treatments do not cure people of HIV or AIDS. Rather, they suppress the virus, even to undetectable levels, but they do not completely eliminate HIV from the body. By suppressing the amount of virus in the body, people infected with HIV caow lead longer and healthier lives. However, they can still transmit the virus and must continuously take antiretroviral drugs in order to maintain their health quality.
HIV/AIDS Treatment Research
NIAID is focused on finding new and more effective therapies, drug classes, and antiretroviral drug combinations that can extend and improve the quality of life for people living with HIV/AIDS. NIAID supports research that advances our understanding of HIV and how it causes disease, thereby unlocking new targets for drug development. Promising medicines are then tested in human clinical trials to determine whether they are safe and effective. This process usually takes several years to complete before a new therapy is available to the public.
At present, HIV positive patients are managed with antiretroviral drugs that prevent the replication of the virus within the body and delay the onset of AIDS. In addition, opportunistic infections in AIDS may be prevented by using drugs targeted against the organisms and the cancers.
Initially in the late 1980s, monotherapy with zidovudine was the only anti-retroviral therapy (ARV). By 1996 more drugs emerged against HIV and combination therapies became more widely used. This highly active combination therapy is now known as highly active anti-retroviral therapy (HAART).
Drug classes
The ARVs mainly act on an enzyme called reverse transcriptase. This enzyme helps in multiplication of the viral particles. The drugs inhibit this enzyme and prevent the viral replication. There are four main classes of drugs that are used as anti-retroviral agents:
1. Nucleoside reverse transcriptase inhibitors (NRTIs)
2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
3. Protease inhibitors
4. Ribonucleotide reductase inhibitor
The drugs, along with their possible side effects, are shown in the table below:
|
Drug Category |
Drug Hame |
Toxicity |
|
Nucleoside reverse transcriptase inhibitors (NRTI) |
Zidovudine (AZT) |
Hepatic steatosis, lactic acidosis, myopathy,cardiomyopathy, dyshaemopoiesis (anaemia, macrocytosis, neutropaenia) |
|
Didanosien (ddI), Stavudine (d4T) |
Hepatic steatosis, lactic acidosi, pancreatitis, myopathy, peripheral neuropathy, dyshaemopoiesis, gynaecomastia |
|
|
Lamivudine (3TC) |
Dyshaemopoiesis |
|
|
Non-Nucleoside reverse transcriptase inhibitors (NNRTI) |
Nevaripine, Efavirenz |
Skin rashes, Stevens-Johnson syndrome, hepatitis |
|
Protease inhibitors (PI) |
Saquinavir, Ritonavir, Indinavir, Nefinavir |
Lipodystrophy, hyperglycaemia,hyperlipidaemia, hepatitis |
|
Ribonucleotide reductase inhibitor (RNR) |
Hydroxyurea |
Bone marrow suppression, mouth ulcers, hepatitis |
Management of HIV positive patients
Management of HIV positive patients according to the British HIV Association (BHIVA) guidelines:
· All patients with HIV infectioeed antiretroviral therapy if they have a CD4 cell count of below 350 cells/mm3 or signs of nervous system involvement. If an AIDS defining condition is present therapy may be indicated despite normal CD4 levels.
· If CD4 cell counts are 351-500 cells/mm3 patients require treatment if they haveHepatitis B or C infection, low percentage of CD4 cells (less than 14%) and have a high risk of heart disease.
· Those with late-stage HIV need ARV except in presence of tuberculosis when CD4 cell counts are more than 350 cells/mm3
How is therapy begun and maintained?
Initial therapy is with three drugs: efavirenz plus tenofovir or abacavir, pluslamivudine or emtricitabine
Patients need vaccination against hepatitis B, pneumococcal disease and Haemophilus influenzae type b (and possibly influenza and hepatitis A). Live viral or organismvaccines like BCG, yellow fever, oral typhoid or live oral polio immunisations should not be administered to these patients.
Those with a risk of opportunistic infections need preventive antifungal or antibiotic agents.
How to manage accidental exposure to HIV infection?
This scenario is common among healthcare workers and those who take care of HIV positive patients. There may be an accidental needle stick injury or exposure to HIV contaminated blood or body fluids of the patients.
Those who have been exposed to the virus within the last 72 hours (three days) need to take anti-HIV medication to possibly prevent the infection.
This is called post-exposure prophylaxis or PEP. PEP must be started within 72 hours of coming into contact with the virus. The quicker PEP is started the better – ideally within hours of coming into contact with HIV.
PEP is a month-long treatment with a combination of antiretroviral drugs, which has serious side effects and does not guarantee absolute protection.
Basic therapy consists of indication of antiviral agents. Use preparations, that inhibit the return transcriptasa of the virus: Azydotymidin (АzТ), Didanosin (ddi), Zalcytobyn (ddc), Stavodin (d4T), Lamivudin , Abacavir (АВС), Nevirapapin (NVP).
Till now monotherapy AZT (Retrovir, Zidovudin) was used. The preparation are prescribed (P.O.) 0,2 gm 3 times per day constantly or courses, duration is not less than 3 months. Treatment will be carried out under the control of the general analysis of a blood with 2 times per one month during the first 2 months and subsequently once per month. In a stage preAIDS (secondary diseases) AZT is necessary to indicate till disappearance of a clinical symptomatology. If the clinical picture is not better Zidovidin is indicated only for that patient in which blood concentration are less than 500 cells in 1 mkl. With such treatment it is possible to prolong patients life, the number of resistant viruses to a preparation however is marked. So, monotherapy AZT is recommended only for prophylaxis of infection of fetus from mother.
Among new means with other mechanism of action use a specific inhibitor of proteases Krixivan, which is effective concerning resistant to AZT populations of a virus 0,8 gm every 8 h. Preparations of a choice may be Rotonavir, Nelfinavir, Sacvinar-SGC, Amprenavir.
Recently it is proved, that efficiency of treatment essentially can be increased using a combination of two or three antiviral preparations. Therefore monotherapy was changed for polytherapy. The most frequently combination of two inhibitors of virus return transcriptasa (stavudin + didanosin, stavudin + lamivudin, zidovudin+didanosin, zidovudin + lamivudin, zidovudin+abacavir) and one inhibitor of a protease is used. At patients with high risk of disease progress (viraemia over 1 000 000 copies / ml.), and also in urgent cases use the two inhibitors of proteases and 1 -2 inhibitors of virus return transcriptasa.
Efficiency of specific treatment is controlled by monitoring with following criteria: 1) level HIV RNA in plasma; 2) quantity of T-lymphocytes CD4; 3) a clinical condition of the patient; 4) morphology and biochemistry of a blood (for detection of undersirable effects of an organism). Level HIV RNA in plasma is researched after 4-8 and 12-16 weeks from the beginning of treatment and subsequently each 3-4 months. The major condition of successful antiretrovirus therapy is its usage during all life of the patient, however it is interfered by a high toxicity of preparations and the complications connected with them. Complete treatment of patients with AIDS remains an unsolved problem. Last combination is considered the most effective, but also it does not cure patients with AIDS.
It is not less important preventive treatment of secondary diseases at AIDS. Against pneumocystic pneumonias the basic agent is Bactrimum. For initial prophylaxis of this disease Bactrimum is indicated 1 tablet duaring 3 days each week. At occurrence of pneumonia daily reception of preparation is prescribed. In case of an intolerance of Bactrim it is possible to indicate Dapsone or Primachin in a combination with Clindamicin. At presence of herpetic infections indicate Acyclovir.
Against criptococus and other funguses use Amphotericinum, against bacteria – the appropriate antibiotic. At sarcoma Kaposhi freezing elements of an eruption by liquid nitrogen, irradiation, chemotherapy are indicated. The immunotherapy of AIDS is at developing stage.
There’s no cure for HIV/AIDS, but a variety of drugs can be used in combination to control the virus. Each of the classes of anti-HIV drugs blocks the virus in different ways. It’s best to combine at least three drugs from two different classes to avoid creating strains of HIV that are immune to single drugs. The classes of anti-HIV drugs include:
· Non-nucleoside reverse transcriptase inhibitors (NNRTIs).NNRTIs disable a proteieeded by HIV to make copies of itself. Examples include efavirenz (Sustiva), etravirine (Intelence) and nevirapine (Viramune).
· Nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs are faulty versions of building blocks that HIV needs to make copies of itself. Examples include Abacavir (Ziagen), and the combination drugs emtricitabine and tenofovir (Truvada), and lamivudine and zidovudine (Combivir).
· Protease inhibitors (PIs). PIs disable protease, another protein that HIV needs to make copies of itself. Examples include atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva) and ritonavir (Norvir).
· Entry or fusion inhibitors. These drugs block HIV’s entry into CD4 cells. Examples include enfuvirtide (Fuzeon) and maraviroc (Selzentry).
· Integrase inhibitors. Raltegravir (Isentress) works by disabling integrase, a protein that HIV uses to insert its genetic material into CD4 cells.
When to start treatment
Current guidelines indicate that treatment should begin if:
· You have severe symptoms
· Your CD4 count is under 500
· You’re pregnant
· You have HIV-related kidney disease
· You’re being treated for hepatitis B
Treatment can be difficult
HIV treatment regimens may involve taking multiple pills at specific times every day for the rest of your life. Side effects can include:
· Nausea, vomiting or diarrhea
· Abnormal heartbeats
· Shortness of breath
· Skin rash
· Weakened bones
· Bone death, particularly in the hip joints
Co-diseases and co-treatments
Some health issues that are a natural part of aging may be more difficult to manage if you have HIV. Some medications that are common for age-related cardiovascular, metabolic and bone conditions, for example, may not interact well with anti-HIV medications. Talk to your doctor about other conditions you’re receiving medication for. There are also known interactions between anti-HIV drugs and:
· Contraceptives and hormones for women
· Medications for the treatment of tuberculosis
· Drugs to treat hepatitis C
Treatment response
Your response to any treatment is measured by your viral load and CD4 counts. Viral load should be tested at the start of treatment and then every three to four months during therapy. CD4 counts should be checked every three to six months.
HIV treatment should reduce your viral load to the point that it’s undetectable. That doesn’t mean your HIV is gone. It just means that the test isn’t sensitive enough to detect it. You can still transmit HIV to others when your viral load is undetectable.
Lifestyle and home remedies
Although it’s important to receive medical treatment for HIV/AIDS, it’s also essential to take an active role in your own care. The following suggestions may help you stay healthy longer:
· Eat healthy foods. Emphasize fresh fruits and vegetables, whole grains and lean protein. Healthy foods help keep you strong, give you more energy and support your immune system.
· Avoid certain foods. Foodborne illnesses can be especially severe in people who are infected with HIV. Avoid unpasteurized dairy products, raw eggs and raw seafood such as oysters, sushi or sashimi. Cook meat until it’s well-done or until there’s no trace of pink color.
· Get immunizations. These may prevent infections such as pneumonia and the flu. Make sure the vaccines don’t contain live viruses, which can be dangerous for people with weakened immune systems.
· Take care with companion animals. Some animals may carry parasites that can cause infections in people who are HIV-positive. Cat feces can cause toxoplasmosis, while pet reptiles can carry salmonella.
Alternative medicine
People who are infected with HIV sometimes try dietary supplements that claim to boost the immune system or counteract side effects of anti-HIV drugs.
Supplements that may be helpful
· Fish oil. Some anti-HIV drugs can cause increases in cholesterol levels. Studies indicate that fish oil supplements can help bring those numbers down.
· Whey protein. Preliminary evidence indicates that whey protein, a cheese by-product, can help some people with HIV gain weight. Whey protein also appears to reduce diarrhea and increase CD4 counts.
Supplements that may be dangerous
· St. John’s wort. Commonly used to combat depression, St. John’s wort can reduce the effectiveness of several types of anti-HIV drugs by more than 50 percent.
· Garlic supplements. Although garlic may help strengthen the immune system, it also interacts with several anti-HIV drugs — reducing their effectiveness by 50 percent. Occasionally eating garlic in food appears to be safe.
Coping and support
Receiving a diagnosis of any life-threatening illness is devastating. But the emotional, social and financial consequences of HIV/AIDS can make coping with this illness especially difficult — not only for you but also for those closest to you.
Fortunately, a wide range of services and resources are available to people with HIV. Most HIV/AIDS clinics have social workers, counselors or nurses who can help you with problems directly or put you in touch with people who can. They can arrange for transportation to and from doctor appointments, help with housing and child care, deal with employment and legal issues, and see you through financial emergencies.
Coming to terms with your illness may be the hardest thing you’ve ever done. For some people, having a strong faith or a sense of something greater than themselves makes this process easier. Others seek counseling from someone who understands HIV/AIDS. Still others make a conscious decision to experience their lives as fully and intensely as they can or to help other people who have the disease.
Prevention
There’s no vaccine to prevent HIV infection and no cure for AIDS. But it’s possible to protect yourself and others from infection. That means educating yourself about HIV and avoiding any behavior that allows HIV-infected fluids — blood, semen, vaginal secretions and breast milk — into your body.
To help prevent the spread of HIV:
· Use a new condom every time you have sex. If you don’t know the HIV status of your partner, use a new condom every time you have anal or vaginal sex. Women can use a female condom. Use only water-based lubricants. Oil-based lubricants can weaken condoms and cause them to break. During oral sex use a condom, dental dam — a piece of medical-grade latex — or plastic wrap.
· Consider the drug Truvada. In July 2012, the Food and Drug Administration (FDA) approved the use of the drug Truvada to reduce the risk of sexually transmitted HIV infection in those who are at high risk. Truvada is also used as an HIV treatment along with other medications.
When used to help prevent HIV infection, Truvada is only appropriate if your doctor is certain you don’t already have an HIV or hepatitis B infection. The drug must also be taken daily, exactly as prescribed. And it should only be used along with other prevention strategies such as condom use every time you have sex.
Truvada isn’t for everyone. If you’re interested in Truvada, talk with your doctor about the potential risks and benefits and whether it’s right for you.
· Tell your sexual partners if you have HIV. It’s important to tell anyone with whom you’ve had sex that you’re HIV-positive. Your partners need to be tested and to receive medical care if they have the virus. They also need to know their HIV status so that they don’t infect others.
· Use a cleaeedle. If you use a needle to inject drugs, make sure it’s sterile and don’t share it. Take advantage of needle-exchange programs in your community and consider seeking help for your drug use.
· If you’re pregnant, get medical care right away. If you’re HIV-positive, you may pass the infection to your baby. But if you receive treatment during pregnancy, you can cut your baby’s risk by as much as two-thirds.
· Consider male circumcision. There’s evidence that male circumcision can help reduce a man’s risk of acquiring HIV
AZT and AIDS
Although some people maintain that treatment with zidovudine (AZT) has compounded the AIDS epidemic (Duesberg, 1992), published reports of both placebo-controlled clinical trials and observational studies provide data to the contrary
In patients with symptomatic HIV disease, for whom a beneficial effect is measured in months, AZT appears to slow disease progression and prolong life, according to double-blind, placebo-controlled clinical studies (reviewed in Sande et al., 1993; McLeod and Hammer, 1992; Volberding and Graham, 1994). A clinical trial known as BW 002 compared AZT with placebo in 282 patients with AIDS or advanced signs or symptoms of HIV disease. In this study, which led to the approval of AZT by the Food and Drug Administration (FDA), only one of 145 patients treated with AZT died compared with 19 of 137 placebo recipients in a six month period. Opportunistic infections occurred in 24 AZT recipients and 45 placebo recipients. In addition to reducing mortality, AZT was shown to have reduced the frequency and severity of AIDS-associated opportunistic infections, improved body weight, prevented deterioration in Karnofsky performance score, and increased counts of CD4+ T lymphocytes in the peripheral blood (Fischl et al., 1987; Richman et al., 1987). Continued follow-up in 229 of these patients showed that the survival benefit of AZT extended to at least 21 months after the initiation of therapy; survival in the original treatment group was 57.6 percent at that time, whereas survival among members of the original placebo group was 51.5 percent at nine months (Richman and Andrews, 1988; Fischl et al., 1989).
In another placebo-controlled study known as ACTG 016, which enrolled 711 symptomatic HIV-infected patients with CD4+ T cell counts between 200 and 500 cells/mm3, those taking AZT were less likely to experience disease progression than those on placebo during a median study period of 11 months (Fischl et al., 1990). In this study, no difference in disease progression was noted among participants who began the trial with CD4+ T cell counts greater than 500/mm3.
A Veteran’s Administration study of 338 individuals with early symptoms of HIV disease and CD4+ T cell counts between 200 and 500 cells/mm3 found that immediate therapy significantly delayed disease progression compared with deferred therapy, but did not lengthen (or shorten) survival after an average study period of more than two years (Hamilton et al., 1992).
Among asymptomatic HIV-infected individuals, several placebo-controlled clinical trials suggest that AZT can delay disease progression for 12 to 24 months but ultimately does not increase survival. Significantly, long-term follow-up of persons participating in these trials, although not showing prolonged benefit of AZT, has never indicated that the drug increases disease progression or mortality (reviewed in McLeod and Hammer, 1992; Sande et al., 1993; Volberding and Graham, 1994). The lack of excess AIDS cases and death in the AZT arms of these large trials effectively rebuts the argument that AZT causes AIDS.
During a 4.5 year follow-up period (mean 2.6 years) of a trial known as ACTG 019, no differences were seen in overall survival between AZT and placebo groups among 1,565 asymptomatic patients entering the study with fewer than 500 CD4+ T cells/mm3 (Volberding et al., 1994). In that study, AZT was superior to placebo in delaying progression to AIDS or advanced ARC for approximately one year, and a more prolonged benefit was seen among a subset of patients.
The Concorde study in Europe enrolled 1,749 asymptomatic patients with CD4+ T cell counts less than 500/mm3. In that study, no statistically significant differences in progression to advanced disease were observed after three years between individuals taking AZT immediately and those who deferred AZT therapy or did not take the drug (Concorde Coordinating Committee, 1994). However, the rate of progression to death, AIDS or severe ARC was slower among the “immediate” AZT group during the first year of therapy. Although the Concorde study did not show a significant benefit over time with the early use of AZT, it clearly demonstrated that AZT was not harmful to the patients in the “immediate” AZT group as compared to the “deferred” AZT group.
A European-Australian study (EACG 020) of 993 patients with CD4+ T cell counts greater than 400/mm3 showed no differences between AZT and placebo arms of the trial during a median study period of 94 weeks, although AZT did delay progression to certain clinical and immunological endpoints for up to three years (Cooper et al., 1993). Both this study and the Concorde study reported little severe AZT-related hematologic toxicity at doses of 1,000 mg/day, which is twice the recommended daily dose in the United States.
Uncontrolled studies have found increased survival and/or reduced frequency of opportunistic infections in patients with HIV disease and AIDS who were treated with AZT or other anti-retrovirals (Creagh-Kirk et al., 1988; Moore et al., 1991a,b; Ragni et al., 1992; Schinaia et al., 1991; Koblin et al., 1992; Graham et al., 1991, 1992, 1993; Longini, 1993; Vella et al., 1992, 1994; Saah et al., 1994; Bacellar et al., 1994). In the Multicenter AIDS Cohort Study, for example, HIV-infected individuals treated with AZT had significantly reduced mortality and progression to AIDS for follow-up intervals of six, 12, 18, and 24 months compared to those not taking AZT, even after adjusting for health status, CD4+ T cell counts and PCP prophylaxis (Graham et al., 1991, 1992).
In addition, several cohort studies show that life expectancy of individuals with AIDS has increased since the use of AZT became common in 1986-87. Among 362 homosexual men in hepatitis B vaccine trial cohorts in New York City, San Francisco, and Amsterdam, the time from seroconversion to death, a period not influenced by variations in diagnosing AIDS, has lengthened slightly in recent years (Hessol et al., 1994). In a Dutch study of 975 males and females with HIV infection, median survival with AIDS increased from nine months in 1982-1985, to 26 months in 1990 (Bindels et al., 1994). Even taking into consideration the benefits of improved PCP prophylaxis and treatment, if AZT were contributing to or causing disease, one would expect a decrease in survival figures, rather than an increase that parallels the use of AZT.
In an analysis from the San Francisco Men’s Health Study, the investigators note that 169 (73 percent) of 233 AIDS patients had been treated with AZT at one time or another. However, 90 (53 percent of the 169) were diagnosed with clinical AIDS before beginning AZT treatment, and another 51 (30 percent of the 169) had CD4+ T cell counts lower than 200/mm3 before initiation of AZT treatment (Ascher et al., 1995). The authors conclude, “These data are not consistent with the hypothesis of a causal role for AZT in AIDS.”
Adherence and Drug Resistance
Photo of a weekly drug organizer.
People infected with HIV who take antiretroviral treatments sometimes find it difficult to adhere to their drug regimens. This may be because it can be hard to take several medicines each day and at different times or because of the unpleasant side effects caused by some medicines, such as nausea and vomiting.
However, when patients fail to take their medicines, HIV has an opportunity to create more variations of itself, including strains that are resistant to antiretroviral drugs. Therefore, it is important for patients to continue taking their medicines as prescribed by their healthcare providers.
Complications and Side Effects
Antiretroviral drugs can, in rare cases, cause serious medical complications, including metabolic changes such as abnormal fat distribution, abnormal lipid and glucose metabolism, and bone loss. Monitoring for these complications and side effects is the responsibility of patients and their healthcare providers.
NIAID supports research aimed at understanding antiretroviral drug-related complications and other side effects, as well as strategies to reduce patient exposure to potentially toxic drug regimens, such as different drug-dosing schedules or combinations, and comparing early versus delayed treatment. NIAID is working to develop simpler, less toxic, and more effective antiretroviral drug regimens.
