Health Topics: /HIV

What is HIV?Image result for hiv virus life cycle

HIV is a virus that gradually attacks the immune system, which is our body’s natural defence against illness. If a person becomes infected with HIV, they will find it harder to fight off infections and diseases. The virus destroys a type of white blood cell called a T-helper cell and makes copies of itself inside them. T-helper cells are also referred to as CD4 cells.1

There are many different strains of HIV – someone who is infected may carry various different strains in their body. These are classified into types, with lots of groups and subtypes. The two main types are:

  • HIV-1: the most common type found worldwide
  • HIV-2: this is found mainly in Western Africa, with some cases in India and Europe.

Basic facts about HIV

  • HIV stands for human immunodeficiency virus.
  • If left untreated, it can take around 10 to 15 years for AIDS to develop, which is when HIV has severely damaged the immune system.
  • With early diagnosis and effective antiretroviral treatment, people with HIV can live a normal, healthy life.
  • HIV is found in the following body fluids of an infected person: semen, blood, vaginal and anal fluids and breast milk.
  • HIV cannot be transmitted through sweat, saliva or urine.
  • According to UK statistics, the most common way for someone to become infected with HIV is by having anal or vaginal sex without a condom.2
  • You can also risk infection by using infected needles, syringes or other drug-taking equipment (blood transmission), or from mother-to-child during pregnancy, birth or breastfeeding.3

What is AIDS?

AIDS is a syndrome caused by the HIV virus.4 It is when a person’s immune system is too weak to fight off many infections, and develops when the HIV infection is very advanced. This is the last stage of HIV infection where the body can no longer defend itself and may develop various diseases, infections and if left untreated, death.

There is currently no cure for HIV or AIDS. However, with the right treatment and support, people can live long and healthy lives with HIV. To do this, it is especially important to take treatment correctly and deal with any possible side-effects.

Basic facts about AIDS

  • AIDS stands for acquired immune deficiency syndrome.
  • AIDS is also referred to as advanced HIV infection or late-stage HIV.
  • Someone with AIDS may develop a wide range of other health conditionsincluding: pneumonia, thrush, fungal infections, TB, toxoplasmosis and cytomegalovirus. 
  • There is also an increased risk of developing other life-limiting conditions, including cancer and brain illnesses. 
  • CD4 count refers to the number of T-helper cells in a cubic millilitre of blood. When a person’s CD4 count drops below 200 cells per millilitre of blood, they are said to have AIDS

    Human Immunodeficiency Virus (HIV) InfectionHuman immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain infections and cancers. Initial infection may cause nonspecific febrile illness. Risk of subsequent manifestations—related to immunodeficiency—is proportional to the level of CD4+ lymphocytes. HIV can directly damage the brain, gonads, kidneys, and heart, causing cognitive impairment, hypogonadism, renal insufficiency, and cardiomyopathy. Manifestations range from asymptomatic carriage to AIDS, which is defined by serious opportunistic infections or cancers or a CD4 count of < 200/?L. HIV infection can be diagnosed by antibody, nucleic acid (HIV RNA), or antigen (p24) testing. Screening should be routinely offered to all adults and adolescents. Treatment aims to suppress HIV replication by using combinations of ? 3 drugs that inhibit HIV enzymes; treatment can restore immune function in most patients if suppression of replication is sustained.

  • Retroviruses are enveloped RNA viruses defined by their mechanism of replication via reverse transcription to produce DNA copies that integrate in the host cell genome. Several retroviruses, including 2 types of HIV and 2 types of human T-lymphotropic virus (HTLV—see HTLV Infections), cause serious disorders in people.

    HIV-1 causes most HIV infections worldwide, but HIV-2 causes a substantial proportion of infections in parts of West Africa. In some areas of West Africa, both viruses are prevalent and may coinfect patients. HIV-2 appears to be less virulent than HIV-1.

    HIV-1 originated in Central Africa in the first half of the 20th century, when a closely related chimpanzee virus first infected humans. Epidemic global spread began in the late 1970s, and AIDS was recognized in 1981.

    In 2015, about 36.9 million people, including 2.6 million children, were living with HIV worldwide, according to the World Health Organization (WHO [ 1]). Almost half do not know they are infected. In 2014, 1.2 million died, and 2 million were newly infected. Most new infections (95%) occur in the developing world, > 1/2 are in women, and 1/7 are in children <15 yr. In many sub-Saharan African countries, incidence is declining markedly from the very high rates of a decade before.

    In the US in 2012, 1.2 million people aged ? 13 yr were estimated to be living with HIV infection; HIV was undiagnosed in about 12.8% of them. About 50,000 new cases are estimated to occur each year in the US. In 2010 (the most recent year for these data), there were 47,500 new cases. Almost two thirds of new infections occurred in gay and bisexual men, and 8 times as many cases occurred in black/African Americans as in whites 

    Symptoms and Signs

    Initial HIV infection

    Initially, primary HIV infection may be asymptomatic or cause transient nonspecific symptoms (acute retroviral syndrome).

    Acute retroviral syndrome usually begins within 1 to 4 wk of infection and usually lasts 3 to 14 days. Symptoms and signs are often mistaken for infectious mononucleosis or benign, nonspecific viral syndromes and may include fever, malaise, fatigue, several types of dermatitis, sore throat, arthralgias, generalized lymphadenopathy, and septic meningitis.

    After the first symptoms disappear, most patients, even without treatment, have no symptoms or only a few mild, intermittent, nonspecific symptoms for a highly variable time period (2 to 15 yr).

    Symptoms during this relatively asymptomatic period may result from HIV directly or from opportunistic infections. The following are most common:

    • Lymphadenopathy

    • White plaques due to oral candidiasis

    • Herpes zoster

    • Diarrhea

    • Fatigue

    • Fever with intermittent sweats

    Asymptomatic, mild-to-moderate cytopenias (eg, leukopenia, anemia, thrombocytopenia) are also common. Some patients experience progressive wasting (which may be related to anorexia and increased catabolism due to infections) and low-grade fevers or diarrhea.

    Worsening HIV infection

    When the CD4 count drops to < 200/?L, nonspecific symptoms may worsen and a succession of AIDS-defining illnesses develop (see AIDS-Defining Illnesses).

    Evaluation may detect infections that do not typically occur in the general population, such as Mycobacterium sp, P. jirovecii, Cryptococcus neoformans, or other fungal infections.

    Infections that also occur in the general population but suggest AIDS if they are unusually severe or frequently recur include herpes zoster, herpes simplex, vaginal candidiasis, and Salmonella septicemia.

    In patients with HIV infection, certain syndromes are common and may require different considerations (see Table: Common Manifestations of HIV Infection by Organ System). Some patients present with cancers (eg, Kaposi sarcoma, B-cell lymphomas) that occur more frequently, are unusually severe, or have unique features in patients with HIV infection (see Cancers Common in HIV-Infected Patients). In other patients, neurologic dysfunction may occur.


    • HIV antibody testing

    • Nucleic acid amplification assays to determine HIV RNA level (viral load)

    HIV infection is suspected in patients with persistent, unexplained, generalized adenopathy or any of the AIDS-defining illnesses (see AIDS-Defining Illnesses). It may also be suspected in high-risk patients with symptoms that could represent acute primary HIV infection.

    Diagnostic tests

    Detection of antibodies to HIV is sensitive and specific except during the first few weeks after infection. Enzyme-linked immunosorbent assay (ELISA) to detect HIV antibodies is highly sensitive, but rarely, results are false-positive. Positive ELISA results are therefore confirmed with a more specific test such as Western blot. However, these tests have drawbacks:

    • ELISA requires complex equipment.

    • Western blot requires well-trained technicians and is expensive.

    • The full testing sequence takes at least a day.

    Newer point-of-care tests using blood or saliva (eg, particle agglutination, immunoconcentration, immunochromatography) can be done quickly (in 15 min) and simply, allowing testing in a variety of settings and immediate reporting to patients. Positive results of these rapid tests should be confirmed by standard blood tests (eg, ELISA with or without Western blot) in developed countries and repetition with one or more other rapid tests in developing countries. Negative tests need not be confirmed.

    If HIV infection is suspected despite negative antibody test results (eg, during the first few weeks after infection), the plasma HIV RNA level may be measured. The nucleic acid amplification assays used are highly sensitive and specific. HIV RNA assays require advanced technology, such as reverse transcription–PCR (RT-PCR), which is sensitive to extremely low HIV RNA levels. Measuring p24 HIV antigen (p24 is a core protein of the virus) by ELISA is less sensitive and less specific than directly detecting HIV RNA in blood.


    When HIV is diagnosed, the following should be determined:

    • CD4 count

    • Plasma HIV RNA level

    Both are useful for determining prognosis and monitoring treatment.

    The CD4 count is calculated as the product of the following:

    • WBC count (eg, 4000 cells/mL)

    • Percentage of WBCs that are lymphocytes (eg, 30%)

    • Percentage of lymphocytes that are CD4+ (eg, 20%)

    Using the numbers above, the CD4 count (4000 x 0.3 x 0.2) is 240 cells/mL, or about 1/3 of the normal CD4 count in adults, which is about 750 ±250/?L.

    Plasma HIV RNA level (viral load) reflects HIV replication rates. The higher the set point (the relatively stable virus levels that occur after primary infection), the more quickly the CD4 count decreases and the greater the risk of opportunistic infection, even in patients without symptoms.


    HIV infection can be staged based on the CD4 count. In patients ? 6 yr, stages are as follows:

    • Stage 1: ? 500 cells/?L

    • Stage 2: 200 to 499 cells/?L

    • Stage 3: < 200 cells/?L

    The CD4 count after 1 to 2 yr of treatment provides an indication of ultimate immune recovery; CD4 counts may not return to the normal range despite prolonged suppression of HIV.

    HIV-related conditions

    Diagnosis of the various opportunistic infections, cancers, and other syndromes that occur in HIV-infected patients is discussed elsewhere in TheManual. Many have aspects unique to HIV infection.

    Hematologic disorders (eg, cytopenias, lymphomas, cancers) are common and may be usefully evaluated with bone marrow aspiration and biopsy. This procedure can also help diagnose disseminated infections with MAC, M. tuberculosis, Cryptococcus, Histoplasma, human parvovirus B19, P. jirovecii, and Leishmania. Most patients have normocellular or hypercellular marrow despite peripheral cytopenia, reflecting peripheral destruction. Iron stores are usually normal or increased, reflecting anemia of chronic disease (an iron-reutilization defect). Mild to moderate plasmacytosis, lymphoid aggregates, increased numbers of histiocytes, and dysplastic changes in hematopoietic cells are common.

    HIV-associated neurologic syndromes can be differentiated via lumbar puncture with CSF analysis and contrast-enhanced CT or MRI (see Table:Common Manifestations of HIV Infection by Organ System and elsewhere in The Manual).

    Screening for HIV

    Screening antibody tests should be offered routinely to adults and adolescents, particularly pregnant women, regardless of their perceived risk. For people at highest risk, especially sexually active people who have multiple partners and who do not practice safe sex, testing should be repeated every 6 to 12 mo. Such testing is confidential and available, often free of charge, in many public and private facilities throughout the world.

    Prognosis-Risk of AIDS, death, or both is predicted by the

    • CD4 count in the short term

    • Plasma HIV RNA level in the longer term

    For every 3-fold (0.5 log10) increase in viral load, mortality over the next 2 to 3 yr increases about 50%. HIV-associated morbidity and mortality vary by the CD4 count, with the most deaths from HIV-related causes occurring at counts of < 50/?L. However, with effective treatment, the HIV RNA level decreases to undetectable levels, CD4 counts often increase dramatically, and risk of illness and death falls but remains higher than that for age-matched populations not infected with HIV.

    Another, less well-understood prognostic factor is the level of immune activation as determined by evaluating the expression of activation markers on CD4 and CD8 lymphocytes. Activation, which may be caused by leakage of bacteria across the HIV-damaged colonic mucosa, is a strong prognostic predictor but is not used clinically because this test is not widely available and antiretroviral therapy changes the prognosis, making this test less important.

    A subgroup of HIV-infected people (termed long-term nonprogressors) remains asymptomatic with high CD4 counts and low HIV levels in the blood without antiretroviral treatment. These people usually have vigorous cellular and humoral immune responses to their infecting HIV strain as measured by assays in vitro. The specificity of this effective response is shown by the following: When these people acquire a superinfection with a second strain of HIV to which their immune response is not as effective, they convert to a more typical pattern of progression. Thus, their unusually effective response to the first strain does not apply to the second strain. These cases provide a rationale for counseling HIV-infected people that they still need to avoid exposure to possible HIV superinfection through unsafe sex or needle sharing.

    Cure of HIV infection has not been thought possible, and thus lifelong drug treatment is considered necessary. However, several recent cases of HIV-infected infants who were treated briefly with antiretroviral therapy after diagnosis and who have remained HIV-negative for many months after stopping treatment suggests that cure is possible in this setting.


Key Points

·         HIV infects CD4+ lymphocytes and thus interferes with cell-mediated and, to a lesser extent, humoral immunity.

·         HIV is spread mainly by sexual contact, parenteral exposure to contaminated blood, and prenatal and perinatal maternal transmission.

·         Frequent viral mutations combined with immune system damage significantly impair the body's ability to clear the HIV infection.

·         Various opportunistic infections and cancers can develop and are the usual cause of death in untreated patients.

·         Diagnose using antibody tests, and monitor by measuring viral load and CD4 count.

·         Treat with a combination of antiretroviral drugs, which can restore immune function to nearly normal in most patients if they take the drugs consistently.

·         Use postexposure and preexposure antiretroviral prophylaxis when indicated.

·         Give primary prophylaxis against opportunistic infections based on the CD4 count.



  • Combinations of antiretroviral drugs (antiretroviral therapy [ART], sometimes called highly active ART [HAART] or combined ART [cART])

  • Chemoprophylaxis for opportunistic infections in patients at high risk

Because disease-related complications can occur in untreated patients with high CD4 counts and because less toxic drugs have been developed, treatment with ART is now recommended for nearly all patients. A few exceptional patients can control their HIV strain without treatment, maintaining very low blood levels of HIV and normal CD4 counts for long periods. These patients may not require ART, but studies to determine whether treating them is helpful have not been done and would be difficult because there are few of these patients and they would likely do well not taking ART for long periods.

Antiretroviral therapy: General principles

ART aims to

  • Reduce the plasma HIV RNA level to undetectable (ie, < 20 to 50 copies/mL)

  • Restore the CD4 count to a normal level (immune restoration or reconstitution)

A poor CD4 count response is more likely if the CD4 count at initiation of treatment is low (especially if < 50/?L) and/or the HIV RNA level is high. However, marked improvement is likely even in patients with advanced immunosuppression. An increased CD4 count correlates with markedly decreased risk of opportunistic infections, other complications, and death. With immune restoration, patients, even those with complications that have no specific treatment (eg, HIV-induced cognitive dysfunction) or that were previously considered untreatable (eg, progressive multifocal leukoencephalopathy), may improve. Outcomes are also improved for patients with cancers (eg, lymphoma, Kaposi sarcoma) and most opportunistic infections.

ART can usually achieve its goals if patients take their drugs > 95% of the time. However, maintaining this degree of adherence is difficult. Partial suppression (failure to lower plasma levels to undetectable levels) may select for single or multiple accumulated mutations in HIV that make viruses partially or completely resistant to a single drug or entire classes of drugs. Unless subsequent treatment uses drugs of other classes to which HIV remains sensitive, treatment is more likely to fail.

Patients with most acute opportunistic infections benefit from early ART (initiated during the management of the opportunistic infection). However, for some opportunistic infections, such as tuberculous meningitis or cryptococcal meningitis, the evidence suggests that ART should be delayed until the first phase of antimicrobial therapy for these infections is finished.

The success of ART is assessed by measuring plasma HIV RNA levels every 8 to 12 wk for the first 4 to 6 mo or until HIV levels are undetectable and every 3 to 6 mo thereafter. Increasing HIV levels are the earliest evidence of treatment failure and may precede a decreasing CD4 count by months. Maintaining patients on failing drug regimens selects for HIV mutants that are more drug-resistant. However, compared with wild-type HIV, these mutants appear less able to reduce the CD4 count, and failing drug regimens are often continued when no fully suppressive regimen can be found.

If treatment fails, drug susceptibility (resistance) assays can determine the susceptibility of the dominant HIV strain to all available drugs. Genotypic and phenotypic assays are available and can help clinicians select a new regimen that should contain at least 2 and preferably 3 drugs to which the HIV strain is more susceptible. The dominant HIV strain in the blood of patients who are taken off antiretroviral therapy may revert over months to years to the wild-type (ie, susceptible) strain because the resistant mutants replicate more slowly and are replaced by the wild type. Thus, if patients have not been treated recently, the full extent of resistance may not be apparent through resistance testing, but when treatment resumes, strains with resistance mutations often reemerge from latency and again replace the wild-type HIV strain.

Classes of antiretrovirals

Multiple classes of antiretrovirals are used in ART (see Table: Antiretroviral Drugs). One class inhibits HIV entry, and the others inhibit one of the 3 HIV enzymes needed to replicate inside human cells; 3 classes inhibit reverse transcriptase by blocking its RNA-dependent and DNA-dependent DNA polymerase activity.

  • Nucleoside reverse transcriptase inhibitors (NRTIs) are phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and terminate synthesis of DNA chains.

  • Nucleotide reverse transcriptase inhibitors (nRTIs) competitively inhibit the HIV reverse transcriptase enzyme, as do NRTIs, but do not require initial phosphorylation.

  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind directly to the reverse transcriptase enzyme.

  • Protease inhibitors (PIs) inhibit the viral protease enzyme that is crucial to maturation of immature HIV virions after they bud from host cells.

  • Entry inhibitors (EIs), sometimes called fusion inhibitors, interfere with the binding of HIV to CD4+ receptors and chemokine co-receptors; this binding is required for HIV to enter cells. For example, CCR-5 inhibitors block the CCR-5 receptor.

  • Integrase inhibitors prevent HIV DNA from being integrated into human DNA.

Some Adverse Effectsb

Entry (fusion) inhibitors



90 mg sc bid

Hypersensitivity reactions, local injection site reactions, peripheral neuropathy, risk of bacterial pneumonia, insomnia, loss of appetite

Maraviroc(CCR5 inhibitor)

150–600 mg bid, depending on other drugs used

Myocardial ischemia or infarction

Integrase inhibitors


50 mg once/day

Headache, insomnia


150 mg once/day

Antiretroviral regimens

Combinations of 3 or 4 drugs from different classes are usually necessary to fully suppress replication of wild-type HIV. The specific drugs are chosen based on the following:

  • Anticipated adverse effects

  • Simplicity of regimen

  • Concomitant conditions (eg, hepatic or renal dysfunction)

  • Other drugs being taken (to avoid drug interactions)

To maximize adherence, clinicians should choose an affordable, well-tolerated regimen that uses once/day (preferable) or bid dosing. Guidelines from expert panels for initiating, selecting, switching, and interrupting therapy and special issues concerning treatment of women and children change regularly and are updated at www.aidsinfo. .

Tablets containing fixed combinations of ? 2 drugs are now widely used to simplify regimens and improve adherence. Common combination tablets include

  • Stribild: Elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, plus tenofovir 300 mg, taken po once/day with food

  • Atripla: Efavirenz 600 mg, tenofovir 300 mg, plus emtricitabine 200 mg, taken po once/day on an empty stomach, preferably at bedtime

  • Complera: Rilpivirine 25 mg, emtricitabine 200 mg, plus tenofovir 300 mg, taken po once/day with food

  • Truvada: Emtricitabine 200 mg plus tenofovir 300 mg, taken once/day po with or without food

  • Triumeq: Dolutegravir 50 mg, lamivudine 300 mg, plus abacavir 600 mg, taken po once/day with or without food

Tablets containing fixed combinations of one drug with a pharmacokinetic enhancer devoid of anti-HIV activity to increase the amount of medicine with HIV activity in the blood can be used. These combinations include

  • Evotaz: Atazanavir 300 mg plus cobicistat 150 mg, taken po once/day with food

  • Prezcobix: Darunavir 800 mg plus cobicistat 150 mg, taken po once/day with food

Adverse effects with combination tablets are the same as those for the individual drugs included.

Drug interactions

Interactions between antiretrovirals may increase or decrease efficacy.

For example, efficacy can be increased by combining a subtherapeutic dose of ritonavir (100 mg once/day) with another PI (eg, lopinavir, amprenavir, indinaviratazanavirtipranavir). Ritonavir inhibits the hepatic enzyme that metabolizes the other PI. By slowing clearance of the therapeutically dosed PI, ritonavir increases the other drug’s levels, maintains the increased levels longer, decreases the dosing interval, and increases efficacy. Another example is lamivudine (3TC) plus zidovudine (ZDV). Use of either drug as monotherapy quickly results in resistance, but the mutation that produces resistance in response to 3TC increases the susceptibility of HIV to ZDV. Thus, when used together, they are synergistic.

Conversely, interactions between antiretrovirals may decrease the efficacy of each drug. One drug may increase elimination of another drug (eg, by inducing hepatic cytochrome P-450 enzymes responsible for elimination). Another, poorly understood effect of some NRTI combinations (eg, ZDV plus stavudine [d4T]) results in decreased antiretroviral activity without increasing drug elimination.

Combining drugs often increases the risk that either drug will have an adverse effect. Possible mechanisms include the following:

  • Hepatic metabolism of PIs by cytochrome P-450: The result is decreased metabolism (and increased levels) of other drugs.

  • Additive toxicities: For example, combining NRTIs, such as d4T and didanosine (ddI), increases the chance of adverse metabolic effects and peripheral neuropathy.

Many drugs may interfere with antiretrovirals (see Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions) ; thus, interactions should always be checked before any new drug is started.

In addition to drug interactions, the following influence activity of some antiretroviral drugs and should be avoided:

  • Grapefruit juice, which inhibits an enzyme in the GI tract that degrades the PI saquinavir and thus increases bioavailability of saquinavir

  • St. John's wort, which can enhance metabolism of PIs and NNRTIs and thus decrease plasma PI and NNRTI levels

Adverse effects of antiretrovirals

Antiretrovirals can have serious adverse effects (see Table: Antiretroviral Drugs). Some of these effects, notably anemia, hepatitis, renal insufficiency, pancreatitis, and glucose intolerance, can be detected by blood tests before they cause symptoms. Patients should be screened regularly, both clinically and with appropriate laboratory testing (CBC; blood tests for hyperglycemia, hyperlidemia, hepatic and pancreatic damage, and renal function; urinalysis), especially after new drugs are started or unexplained symptoms develop.

Metabolic effects consist of interrelated syndromes of fat redistribution, hyperlipidemia, and insulin resistance. Subcutaneous fat is commonly redistributed from the face and extremities to the trunk, neck, breasts, and abdomen—a cosmetic effect that can stigmatize and distress patients. Treating the resulting deep facial grooves with injected collagen or polylactic acid can be beneficial.

Central obesity, hyperlipidemia, and insulin resistance, which together constitute the metabolic syndrome, increase the risk of MI, stroke, and dementia.

Antivirals from all classes appear to contribute to these metabolic effects, but PIs are the most clearly involved. Some drugs, such as ritonavir or d4T, commonly have metabolic effects. Others, such as tenofoviretravirineatazanavir or darunavir (even when combined with low-dose ritonavir),raltegravir, and maraviroc, appear to have small to minimal effects on lipid levels.

Mechanisms for metabolic effects appear to be multiple; one is mitochondrial toxicity. Risk of metabolic effects (highest with PIs) and mitochondrial toxicity (highest with NRTIs) varies by drug class and within drug classes (eg, among NRTIs, highest with d4T).

Metabolic effects are dose-dependent and often begin in the first 1 to 2 yr of treatment. Nonalcoholic steatohepatitis and lactic acidosis are uncommon but can be lethal. Long-term effects and optimal management of metabolic effects are unclear. Lipid-lowering drugs (statins) andinsulin -sensitizing drugs (glitazones) may help. (See also the recommendations of the HIV Medicine Association of the Infectious Diseases Society of America and the Adult AIDS Clinical Trials Group: Guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiretroviral therapy .)

Bone complications of ART include asymptomatic osteopenia and osteoporosis, which are common. Uncommonly, osteonecrosis of large joints such as the hip and shoulder causes severe joint pain and dysfunction. Mechanisms of bone complications are poorly understood.

Immune reconstitution inflammatory syndrome (IRIS)

Patients beginning ART sometimes deteriorate clinically, even though HIV levels in their blood are suppressed and their CD4 count increases, because of an immune reaction to subclinical opportunistic infections or to residual microbial antigens after successful treatment of opportunistic infections. IRIS usually occurs in the first months of treatment but is occasionally delayed. IRIS can complicate virtually any opportunistic infection and even tumors (eg, Kaposi sarcoma) but is usually self-limited or responds to brief regimens of corticosteroids.

Determining whether clinical deterioration is caused by treatment failure, IRIS, or both requires assessment of the persistence of active infections with cultures and can be difficult.

Interruption of antiretroviral therapy

Interruption of ART is usually safe if all drugs are stopped simultaneously, but levels of slowly metabolized drugs (eg, nevirapine) may remain high and thus increase the risk of resistance. Interruption may be necessary if intervening illnesses require treatment or if drug toxicity is intolerable or needs to be evaluated. After interruption to determine which drug is responsible for toxicity, clinicians can safely restart most drugs as monotherapy for up to a few days. Note: The most important exception is abacavir; patients who had fever or rash during previous exposure toabacavir may develop severe, potentially fatal hypersensitivity reactions with reexposure.

End-of-life care

Although antiretroviral therapy has dramatically increased life expectancy for patients with AIDS, many patients still deteriorate and die. Death may result from the following:

  • Inability to take ART consistently, resulting in progressive immunosuppression

  • Occurrence of untreatable opportunistic infections and cancers

  • Liver failure due to hepatitis B or C

  • Accelerated aging and age-related disorders

Death is rarely sudden; thus, patients usually have time to make plans. Nonetheless, patients should record their plans for health care early, with clear instructions for end-of-life care. Other legal documents, including powers of attorney and wills, should be in place. These documents are particularly important for homosexual patients because protection of assets and rights (including visitation and decision-making) for their partners may be problems.

As patients near the end of life, clinicians may need to prescribe drugs to relieve pain, anorexia, agitation, and other distressing symptoms. The profound weight loss in many people during the last stages of AIDS makes good skin care difficult. The comprehensive support provided by hospice programs helps many patients because hospice providers are unusually skilled at symptom management, and they support caregivers and patient autonomy.

Medicinent/ /msdmanuals/Web md

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