Andy Jones is a 30-year-old IT worker who has been suffering from increasingly severe diarrhoea for about 3 months. Taking loperamide (Imodium) has had little effect. Andy looks unwell and has lost weight since the last consultation, and though the previous microbiology results of stool cultures were negative, the GP decides to repeat the investigation and request a full blood count.
Full blood count: haemoglobin, 10.5g/dl [normal range (for males): 13.0-17.0 g/dl]; total white blood cells count was normal but there was a reduced number of lymphocytes. The Microbiology laboratory reported Cryptosporidium detected in the stools.
She asked him if it were possible that he could have been in contact with HIV, and after much hesitation, he finally admitted that although he was married with two children, unknown to his wife, he had had a number of homosexual encounters.
The GP asked permission to test him for HIV and AIDS, explaining what the consequences were. The results showed a positive result for antibodies to HIV proteins and a CD4 count which was very low (110 /mm3; normal range 500-1500/mm3).
He was referred to a consultant in AIDS/HIV medicine who prescribed HAART (Highly Active Anti-Retroviral Therapy). Andy was reassured that his life expectancy was excellent, if his treatment compliance was good.
Diarrhoea: Frequent bowel evacuation or the passage of abnormally soft or liquid faeces. It may be caused by intestinal infections, other forms of intestinal inflammation, malabsorption, anxiety, and the irritable bowel syndrome. Severe or prolonged diarrhoea may lead to excess losses of fluid, salts, and nutrients in the faeces.
(Oxford Medical Dictionary)
Loperamide: A drug used in the treatment of diarrhoea. It acts by reducing peristalsis of the digestive tract and is administered by mouth: side effects are rare, but include abdominal distension, drowsiness, and skin rash.
(Oxford Medical Dictionary)
Cryptosporidium: A protozoan pathogen which is most commonly isolated in HIV positive patients presenting with diarrhoea, causing an illness known as Cryptosporidiosis. Most patients recover in 7-14 days but the disease persists in the immunocompromised (including AIDS patients).
(Oxford Medical Dictionary, Wikipedia and Kumar & Clark)
CD4 cells- T-helper cells which have molecules called CD4 on its surface. These "helper" cells initiate the body's response to invading micro-organisms such as viruses. HIV is a retrovirus, meaning it needs cells from a "host" in order to make more copies of itself (replication). In the case of HIV, CD4 cells are the host cells that aid HIV in replication. HIV attaches to the CD4 cells, allowing the virus to enter and infect the CD4 cells, damaging them in the process. The fewer functioning CD4 cells, the weaker the immune system and therefore the more vulnerable a person is to infections and illnesses. Knowing how many functioning CD4 cells are circulating in the blood gives the HIV doctor an idea of how strong the HIV+ person's immune system really is. A simple blood test called the CD4 count measures the number of functioning CD4 cells in the body and therefore measures the health of the immune system. The CD4 blood test results can vary a great deal. In a healthy adult, a normal CD4 count can vary a great deal but is typically 600 to 1200 cells per cubic millimetre of blood.
(http://aids.about.com/od/newlydiagnosed/qt/cd4.htm)
HIV: The Human Immunodeficiency Virus (HIV) is a sexually transmitted virus (STI) that attacks the body's immune system, which provides a natural defence system against disease and infection. HIV infects special cells, called CD4 cells, which are found in your blood, and are responsible for fighting infection. After becoming infected, the CD4 cells are destroyed by HIV. Although the body will attempt to produce more CD4 cells, their numbers will eventually decline and the immune system will stop working. This leaves a person who is infected with HIV with a high risk of developing a serious infection, or disease, such as cancer.
(http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=196)
AIDS: Acquired Immune Deficiency Syndrome (AIDS) is a term that is used to describe the latter stages of HIV, when the immune system has stopped working and the person develops a life-threatening condition, such as pneumonia (infection of the lungs). The term 'AIDS' was first used by doctors when the exact nature of the HIV virus was not fully understood. However, the term is no longer widely used because it is too general to describe the many different conditions that can affect somebody with HIV. Specialists now prefer use the terms 'advanced', or 'late stage' HIV infection.
(http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=196)
Retrovirus: HIV is a special type of virus known as a retrovirus. Retroviruses spread by breaking down the DNA in our cells and then reassembling it to make copies of itself. Retroviruses are challenging to treat as they can rapidly alter (mutate) into new strains of virus.
(http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=196)
ARC: AIDS related complex. A term used to describe people with HIV infection who have only mild symptoms of illness such as swollen lymph glands. The term is rarely used today.
(http://www.medterms.com/script/main/art.asp?articlekey=10924)
The relationship between Cryptosporidium and Diarrhoea and its link with HIV and how it is an ARC:
Cryptosporidiosis is an uncommon infection to patients who are HIV positive. It is the chief AIDS-determining infection in no more than 2% of reported cases but is seen with considerably greater frequency in patients living with AIDS. Some studies have shown a higher incidence of cryptosporidiosis in patients with sexually-acquired HIV infection than in those with IV drug-related HIV infection, most likely due to contact with faeces during anal-oral sex.
Although cryptosporidiosis can be acquired at any time during the course of HIV infection, including primary infection, major morbidity and mortality occur almost exclusively in patients with CD4 counts below 180 cells/mm3; above this level, spontaneous recovery generally occurs. Patients with CD4 counts below 50 cells/mm3 usually experience progressive diarrhoea that results in death.
The most common clinical presentation of cryptosporidiosis in HIV-infected patients is an acute onset of non-bloody, watery diarrhoea without fever. In patients with CD4 counts greater than 180 cells/mm3, as in immunocompetent HIV-negative individuals, cryptosporidiosis is a self-limiting condition that lasts from 5 to 14 days, although transient relapses may occur in up to 30% of cases. In patients with AIDS, cryptosporidiosis is, commonly, a permanent diarrhoeal illness that leads to chronic malabsorption of fluids, nutrients, vitamins, and electrolytes -- with resulting wasting and hypokalemic metabolic acidosis. In patients who fail to respond to therapy, death usually occurs in three to six months.
Multiple pathogens may be present. A single stool specimen, treated with modified acid-fast (Kinyoun) stain, is usually adequate for diagnosis, but occasionally a repeat specimen, or even a duodenal aspirate or biopsy, is necessary.
(http://www.thebody.com/content/art12553.html)
What is the HIV test, and what is the significance of the CD4 count?
HIV tests are used to detect the presence of the human immunodeficiency virus in serum, saliva, or urine. Such tests may detect HIV antibodies, antigens, or RNA. HIV antibody tests are specifically designed for routine diagnostic testing of adults; these tests are inexpensive and extremely accurate.
The ELISA test, or the enzyme immunoassay (EIA), was the first screening test commonly employed for HIV. It has a high sensitivity. In an ELISA test, a person's serum is diluted 400-fold and applied to a plate to which HIV antigens have been attached. If antibodies to HIV are present in the serum, they may bind to these HIV antigens. The plate is then washed to remove all other components of the serum. A specially prepared "secondary antibody" â€" an antibody that binds to human antibodies â€" is then applied to the plate, followed by another wash. This secondary antibody is chemically linked in advance to an enzyme. Thus the plate will contain enzyme in proportion to the amount of secondary antibody bound to the plate. A substrate for the enzyme is applied, and catalysis by the enzyme leads to a change in colour or fluorescence. ELISA results are reported as a number; the most controversial aspect of this test is determining the "cut-off" point between a positive and negative result.
In the Western blot procedure, cells that may be HIV-infected are opened and the proteins within are placed into a slab of gel, to which an electrical current is applied. Different proteins will move with different velocities in this field, depending on their size, while their electrical charge is levelled by a surfactant called sodium lauryl sulphate. Once the proteins are well-separated, they are transferred to a membrane and the procedure continues similar to an ELISA: the person's diluted serum is applied to the membrane and antibodies in the serum may attach to some of the HIV proteins. Antibodies which do not attach are washed away, and enzyme-linked antibodies with the capability to attach to the person's antibodies determine to which HIV proteins the person has antibodies.
There are no universal criteria for interpreting the Western blot test: the number of viral bands which must be present may vary. If no viral bands are detected, the result is negative. If at least one viral band for each of the GAG, POL, and ENV gene-product groups is present, the result is positive. The three-gene-product approach to Western blot interpretation has not been adopted for public health or clinical practice. Tests in which less than the required number of viral bands is detected are reported as indeterminate: a person who has an indeterminate result should be retested, as later tests may be more conclusive. Almost all HIV-infected persons with indeterminate Western-Blot results will develop a positive result when tested in one month; persistently indeterminate results over a period of six months suggest the results are not due to HIV infection. In a generally healthy low-risk population, indeterminate results on Western blot occur on the order of 1 in 5,000 patients. The Western blot test is referred to as the 'Gold Standard', meaning it trumps any positive ELISA test.
The p24 antigen test detects the presence of the p24 protein of HIV (also known as CA), a major core protein of the virus. Monoclonal antibodies specific to the p24 protein are mixed with the person's blood. Any p24 protein in the person's blood will stick to the monoclonal antibody and enzyme-linked antibody to the monoclonal antibodies to p24 causes a colour change if p24 was present in the sample.
This test is no longer used routinely in the US or the EU to screen blood donations since the objective was to reduce the risk of false negatives in the window period. Nucleic acid testing (NAT) is more effective for this purpose, and p24 antigen testing is no longer indicated if a NAT test is performed. The p24 antigen test is not useful for general diagnostics, as it has very low sensitivity and only works during a certain time period after infection before the body produces antibodies to the p24 protein.
The CD4 T-cell count is not an HIV test, but rather a procedure where the number of CD4 T-cells in the blood is determined. It does not check for the presence of HIV. It is used to monitor immune system function in HIV-positive people. Declining CD4 T-cell counts are considered to be a marker of progression of HIV infection. In HIV-positive people, AIDS is officially diagnosed when the count drops below 200 cells/μL or when certain opportunistic infections occur. This use of a CD4 count as an AIDS criterion was introduced in 1992; the value of 200 was chosen because it corresponded with a greatly increased likelihood of opportunistic infection. Lower CD4 counts in people with AIDS are indicators that prophylaxis against certain types of opportunistic infections should be instituted.
Low CD4 T-cell counts are associated with a variety of conditions, including many viral infections, bacterial infections, parasitic infections, sepsis, tuberculosis, coccidioidomycosis, burns, trauma, intravenous injections of foreign proteins, malnutrition, over-exercising, pregnancy, normal daily variation, psychological stress, and social isolation.
This test is also used occasionally to estimate immune system function for people whose CD4 T cells are impaired for reasons other than HIV infection, which include several blood diseases, several genetic disorders, and the side effects of many chemotherapy drugs.
Generally speaking, the lower the number of T cells, the lower the immune system's function will be. Normal CD4 counts are between 500 and 1500 CD4+ T cells/microlitre, and the counts may fluctuate in healthy people depending on recent infection status, nutrition, exercise and other factors. Women tend to have somewhat lower counts than men.
Duo/combined tests are also available which combine antigen and antibody testing, thereby making earlier detection possible.
(http://en.wikipedia.org/wiki/HIV_test)
What is HAART and how does it work? What is the course of treatment and the prognosis?
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as highly active antiretroviral therapy, or HAART.
Antiretroviral drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits.
Nucleoside & nucleotide reverse transcriptase inhibitors (NRTI) inhibit reverse transcription by being incorporated into the newly synthesized viral DNA and preventing its further elongation.
Non-nucleoside reverse transcriptase inhibitors (nNRTI) inhibit reverse transcriptase directly by binding to the enzyme and interfering with its function.
Protease inhibitors (PIs) target viral assembly by inhibiting the activity of protease, an enzyme used by HIV to cleave nascent proteins for final assembly of new virons.
Integrase inhibitors inhibit the enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial, and raltegravir became the first to receive FDA approval in October 2007.
Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. Maraviroc and enfuvirtide are the two currently available agents in this class.
Maturation inhibitors inhibit the last step in gag processing in which the viral capsid polyprotein is cleaved, thereby blocking the conversion of the polyprotein into the mature capsid protein (p24). Because these viral particles have a defective core, the virions released consist mainly of non-infectious particles. There are no drugs in this class currently available, though two are under investigation, bevirimat and Vivecon.
The life cycle of HIV can be as short as about 1.5 days from viral entry into a cell, through replication, assembly, and release of additional viruses, to infection of other cells. HIV lacks proofreading enzymes to correct errors made when it converts its RNA into DNA via reverse transcription. Its short life cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic variability of HIV. Most of the mutations either are inferior to the parent virus (often lacking the ability to reproduce at all) or convey no advantage, but some of them have a natural selection superiority to their parent and can enable them to slip past defences such as the human immune system and antiretroviral drugs. The more active copies of the virus, the greater the possibility that one resistant to antiretroviral drugs will be made, so antiretroviral combination therapy defends against resistance by suppressing HIV replication as much as possible.
Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation. If a mutation arises that conveys resistance to one of the drugs being taken, the other drugs continue to suppress reproduction of that mutation. With rare exceptions, no individual antiretroviral drug has been demonstrated to suppress an HIV infection for long; these agents must be taken in combinations in order to have a lasting effect. As a result, the standard of care is to use combinations of antiretroviral drugs. Combinations usually comprise two nucleoside-analogue RTIs and one non-nucleoside-analogue RTI or protease inhibitor. This three drug combination is commonly known as a triple cocktail.
The use of Highly Active Antiretroviral Therapy (HAART; drugs which slow down the rate at which HIV is able to reproduce) from the mid-1990s onwards, has led to dramatic improvements in the prognosis of people with HIV. For instance, AIDS deaths in the UK have fallen from a peak of over 1,500 in 1994 to approximately 400 a year at the moment. The AIDS deaths which still occur in this country commonly affect people who are diagnosed with HIV late in the disease process, when their immune system is already quite damaged.
Research into the prognosis of people starting HAART indicates that the risk of becoming very ill or dying because of HIV within the next three years is linked to five key factors: having a CD4 count below 200 or a viral load above 100,000 at the time of starting treatment; being aged over 50; being an injecting drug user; or having had a prior AIDS-defining illness.
In the UK it is recommended that anti-HIV treatment is started before your CD4 count falls below 200, an indication that HIV has damaged your immune system to such an extent that you are vulnerable to serious illness. It is also strongly recommended that you start anti-HIV drugs if you become ill because of HIV. Starting treatment in these circumstances has been shown to improve prognosis compared to delaying treatment until later.
(http://en.wikipedia.org/wiki/Antiretroviral_drug)
(http://www.aidsmap.com/en/docs/838DDDA5-614F-488A-BE41-BA4DBE1AA4EC.asp#b7158738-67b5-4bee-b527-0d8d28b38b56)
How should the doctor address social issues?
Rather than the doctor, social workers are responsible for addressing the social issues of an HIV patient. Counselling in HIV and AIDS has become a core element in a holistic model of health care, in which psychological issues are recognised as integral to patient management. HIV and AIDS counselling has two general aims: the prevention of HIV transmission and the support of those affected directly and indirectly by HIV. It is vital that HIV counselling should have these dual aims because the spread of HIV can be prevented by changes in behaviour. One to one prevention counselling has a particular contribution in that it enables frank discussion of sensitive aspects of a patient's life- such discussion may be hampered in other settings by the patient's concern for confidentiality or anxiety about a judgmental response. Also, when patients know that they have HIV infection or disease, they may suffer great psychosocial and psychological stresses through a fear of rejection, social stigma, disease progression, and the uncertainties associated with future management of HIV. Good clinical management requires that such issues be managed with consistency and professionalism, and counselling can both minimise morbidity and reduce its occurrence. All counsellors in this field should have formal counselling training and receive regular clinical supervision as part of adherence to good standards of clinical practice.
(http://www.bmj.com/cgi/content/full/322/7301/1533)
