The advent of effective antiretroviral therapy over the past 10 years has revolutionised the management of HIV infection in the western world, leading to increased life expectancy among patients with HIV.
Most HIV positive (HIV+) patients are looked after in specialist units.
Treatment of HIV with antiretroviral drugs is a complex area and there is no sign of drug initiation moving into primary care in the near future.
Nevertheless GPs have an increasingly important role in the care of HIV+ patients.
Primary infection phase
When someone is exposed to HIV, the virus enters CD4+ T-cells and, to a lesser extent, macrophages. A few weeks after infection an initial burst of viral replication occurs in these immune cells. This corresponds to a high viral load and a dramatic fall in CD4 count.
This primary HIV infection phase is often associated with fever, sore throat, rash and lymphadenopathy. This is the time of peak infectivity to others and opportunistic infection can occur.
This is followed by an antiviral immune response. The viral load falls to a 'set point' that is maintained for several years. The CD4 count rises again in the peripheral blood but by now much of the total body CD4+ T-cell population, which resides in the gut and lymph nodes, has been destroyed.
A person in this 'latent' stage of infection still has active viral replication and increased susceptibility to infection.
HIV has a predilection for activated and HIV-specific CD4+ T-cells so, over time, the anti-HIV immune response wanes and the viral load gradually starts to rise. The CD4 count falls and the patient becomes increasingly susceptible to infection.
At a CD4 count of about 200 x 106 cells/mm3 (a normal count is 500-1,500 x 106 cells/mm3) infections that are not seen in immunocompetent people start to emerge. HIV itself can also cause a variety of symptoms and clinical manifestations at variable points of the disease.
This course of events can be interrupted at any time by antiretroviral therapy. Although the peripheral blood CD4 count often normalises on treatment, the total body CD4+ T-cell population probably remains low and the immune system remains suboptimal.
So although antiretroviral therapy dramatically improves the prognosis for patients with HIV, they can never regain full immune competence.
HIV+ patients can experience a vast array of symptoms such as malaise, myalgia, sweats, fever, lymphadenopathy, weight loss and skin changes.
These are all much more common with uncontrolled viral replication and can be similar to the symptoms of primary HIV infection. Some can be difficult to differentiate from common community illnesses. In general, if symptoms are due to HIV, they will persist.
HIV is a multi-system disease. Bone marrow, heart, lungs, skin and kidneys may be involved and infection can have devastating neurological consequences.
The advent of therapy has seen a dramatic reduction in complications although GPs should be aware of these conditions, particularly in patients not yet being treated.
Bacterial infection is more common in HIV+ patients at any CD4 count.
Respiratory tract infections are common, especially acute bronchitis and bacterial and viral URTI. Diarrhoea is another frequent presentation and stool cultures should always be sent.
The threshold for antibiotic treatment should be lower in HIV+ patients.
Oral candidiasis can be safely treated with single-dose oral fluconazole in the community.
HIV is associated with skin complaints including acne, folliculitis and molluscum contagiosum. Frequently, these conditions accompany other HIV-related symptoms and antiretroviral therapy is required. Psoriasis gets notably worse with HIV infection as the CD4 count falls.
Anaemia is common and may be caused by HIV directly, by infection or by drugs such as zidovudine and co-trimoxazole. Abnormal liver function warrants investigation for viral hepatitis, although drugs are often the culprit. Renal failure is also often caused by drugs but HIV can be associated with a nephropathy (mostly in Africans) related to a high viral load.
Newly diagnosed patients
Newly diagnosed patients should be referred for a specialist opinion and consideration of treatment. A full history and thorough physical examination should be performed, partly to uncover any signs of infection.
Patients should be evaluated with regard to the effect of the diagnosis on their mental health and may need a period of psychological support.
At this time health screening should be performed, and risk stratification for conditions that may affect the projected long-term management of HIV, particularly cardiovascular disease. The patient should also be screened for other STIs.
Indications for emergency hospital admission are based on clinical judgment, as for any patient group. HIV+ patients are also at increased risk for conditions such as pulmonary embolism, MI, and liver and kidney disease.
Pneumocystis pneumonia (PCP) classically presents insidiously with a dry cough, shortness of breath and oxygen desaturation on exertion (useful only on the first episode).
Neurological problems are much more common in HIV+ patients than in the general population, especially in young people. They are commonly due to toxoplasmosis, lymphoma, TB or viruses. Any new neurological symptom or sign should be referred as an emergency.
Tests usually done at baseline are: full blood count; U&Es and creatinine; LFTs; glucose; lipid profile; serological tests for cytomegalovirus (CMV), toxoplasmosis, hepatitis A, B and C; chest X-ray and ECG.
Investigations specific to HIV are CD4 count and plasma HIV-1 RNA viral load. In certain specialist settings, a baseline antiretroviral drug resistance test will be made.
An HIV+ patient with a CD4 count of less than 200 should be commenced on chemoprophylaxis against opportunistic infection. The regimen will vary according to how low the CD4 count is and what infections the patient has had in the past.
The first drug is usually co-trimoxazole - 960mg once daily is given for prophylaxis against PCP, which is also effective at preventing toxoplasmosis.
When the CD4 count drops to 50 or below, clarithromycin (500mg twice daily) or azithromycin (1250mg weekly) is started to prevent Mycobacterium avium infection.
If the patient has a history of CMV infection, ganciclovir prophylaxis is continued after a course of treatment. Aciclovir prophylaxis is sometimes given if the patient experiences particularly troublesome herpes reactivation or shingles. Fluconazole prophylaxis is given if the patient has had cryptococcal meningitis.
All of these drugs can safely be stopped once the CD4 count has risen adequately on antiretroviral treatment.
Patients with an AIDS-defining diagnosis or a CD4 count of less than 200-250 benefit from antiretroviral therapy.
In addition, patients with constitutional symptoms of HIV usually feel better on treatment, whatever the CD4 count (although it is usually low).
When to treat patients with a CD4 count over 250 is the subject of debate.[QQ/] The original suggestion was that treatment should be delayed until drug toxicity was outweighed by the risk of opportunistic infection.
However, the SMART study, a large randomised controlled trial, has shown that interrupting treatment when the CD4 count is high (over 350 in this case) led to lower average CD4 counts, more infections and higher mortality.
Also, interrupting treatment was associated with higher rates of liver, kidney and heart disease. Modern first-line antiretroviral therapy is generally well tolerated and non-toxic and, if adhered to correctly, can provide durable viral suppression for long periods of time.
Dr Turtle is specialist registrar in infectious diseases and tropical medicine at Royal Liverpool University Hospital, and Dr Thakkar is a GP in Wooburn Green, Buckinghamshire
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- Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr W M, Lundgre J D et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355: 2,283-96.