Complications of HIV Infection

Most complications of HIV/AIDS are as a result of suppression of T-cell mediated immunity. Antiretroviral therapy (ART) is available to inhibit the replication of the human immunodeficiency virus.^[1] ART is increasingly replacing the term HAART (highly active antiretroviral therapy) in common usage. ART helps to prolong life, restore the patient's immune system to something approaching normal activity and reduce the chances of opportunistic infection. Indeed, early use of ART has increased survival to near-normal duration and dramatically reduced the risk of developing AIDS (or late-stage HIV disease, as it is increasingly being called). Combinations of three or more drugs are given to lessen the possibility of resistance.

For more information see separate articles Acquired Immune Deficiency Syndrome (AIDS) and Human Imunodeficiency Virus (HIV).

Pulmonary complications

Pneumocystis jirovecii pneumonia^[2]

Pneumocystis carinii is now known as Pneumocystis jirovecii. It has been one of the hallmarks of late-stage HIV disease but is now less common because of antiretroviral therapy (ART) and primary prophylaxis.^[3] Nevertheless, it remains a significant cause of pathology and is increasing in non-AIDS immunosuppressed patients (mainly transplant recipients) in whom a reservoir of infection is maintained. Most late-stage HIV disease cases occur with a CD4 count <200/mm³ and mainly at <100/mm³.

• Presentation: typically, develops over a few weeks and includes shortness of breath, dry cough and fever. There may also be malaise, fatigue, weight loss and chest pain. Diagnosing pneumocystis pneumonia may pose a real challenge for GPs. There may be surprisingly few signs in the chest apart from a few minor crepitations, and radiology may be unhelpful.^[4]
• Investigations:
  • Lactate dehydrogenase (LDH) level reflects lung damage and is often higher in AIDS than in other pneumocystis-related pathology.
  • CXR may show bilateral perihilar interstitial shadowing (but may be normal).^[2]
  • Oxygen saturation <95% at rest or falls after exercise.
  • Microscopy of sputum may show P. jirovecii cysts and trophozoites with staining.
  • CT scanning and gallium ⁶⁷ Ga scanning are occasionally used in equivocal cases.
  • Bronchoscopy may be needed - additional findings may be tuberculosis (TB),fungal infections and Kaposi's sarcoma.
• Treatment:
  • High-dose co-trimoxazole is recommended for three weeks first-line.
  • Intravenous (IV) co-trimoxazole should be given in moderate-to-severe cases but there is a high level of side-effects. Other options include IV clindamycin andprimaquine. This combination is considered to be more effective than IVpentamidine. Studies suggest that low-dose co-trimoxazole is as effective as higher doses for HIV patients and causes fewer side-effects; however, further research is needed.
  • IV steroids may be helpful in moderate-to-severe pneumonia, eg IVmethylprednisolone or oral prednisolone for 5-10 days.
  • Oxygen may also be beneficial.
  • The survival of HIV-related pneumocystis pneumonia patients given ART is improved by admission to intensive care units.^[5]

  Bacterial pneumonia^[6]

  The most common causes are Streptococcus pneumoniae, Haemophilus influenzaeand Moraxella catarrhalis. In advanced cases, causative organisms may includeStaphylococcus aureus, Klebsiella spp. and other Gram-negative rods. The presentation may be atypical, with diffuse infiltrates appearing on the X-ray.

  Fungal infections

  These may include Cryptococcus spp. In disseminated infection other fungi may be involved. The first-line treatment for most fungal lung infections is IV amphotericin.^[7]

  TB^[8]

  This is very common in areas where TB is endemic. Many cases represent reactivation of previous infection. HIV-positive patients with TB are less likely to be sputum-positive with X-rays that show less cavitation and more involvement of lower lobes. They are more likely to relapse after completion of treatment and die prematurely. Treatment is the standard 3-4 drug regimen but multidrug-resistant TB strains are becoming more frequent.^[9] One study found that TB preventative therapy (eg isoniazid, co-trimoxazole) was useful in reducing the incidence of infection and death in children with HIV, irrespective of whether they also received ART.^[10]
  
   

  Mycobacterium avium complex

  This is seen In late-stage HIV disease. Patients with CD4 <50/mm³ are at high risk. In industrialised countries, it is reported in 40% of patients with AIDS:
  • Presentation: infection is disseminated and presents with fever, night sweats, weight loss, diarrhoea, abdominal pain, anaemia or hepatic dysfunction.
  • Diagnosis: this is by culture from blood or bone marrow or may be recognised in tissue biopsy.
  • Treatment: studies suggest the best regime for most strains is rifamycin, ethambutol and a macrolide. However, for M. simiae a combination of macrolide, moxifloxacin and an additional drug such as IV amikacin is beneficial.^[11] Recently, trials have shown benefit from the use of aerolised rather than IV amikacin.^[12]

  Central nervous system complications^[13]

  Cerebral toxoplasmosis

  Toxoplasmosis is less common than it was, since the advent of ART, although is still prevalent in resource-poor countries. Cerebral toxoplasmosis is the most frequent central nervous system (CNS) infection when CD4 <200/mm³. It usually occurs due to reactivation of cysts in the brain, causing local lesions, typically multiple.
  • Presentation: subacute symptoms include focal neurological disturbances, headache, confusion, fever and seizures.
  • Investigations:
    • CT scan: the appearance is of a mass with a ring of contrast enhancement and associated oedema.
    • MRI: this may show lesions not visible on CT.
    • Polymerase chain reaction (PCR) test: may be helpful.
  • Treatment: the usual practice is to treat these symptoms as toxoplasmosis and consider biopsy if there is no improvement in 7-10 days. Treatment is sulfadiazineand pyrimethamine plus folinic acid (high level of side-effects and clindamycin can be used instead of sulfadiazine). Trimethoprim-sulfamethoxazole is no more effective but may be better tolerated.^[14] Steroids may be used for cerebral oedema.

  Cryptococcal meningitis^[15]

  • Presentation: this is usually subacute with nonspecific symptoms such as headache, vomiting and a slight fever. Neurological signs are not a major feature. Less commonly, patients present with psychiatric symptoms, convulsions, cranial nerve palsies or truncal ataxia.
  • Investigations: these reveal focal neurological lesions. Diagnosis is by identifying organisms in the cerebrospinal fluid (CSF).
  • Treatment: amphotericin plus 5-flucytosine are first-line therapy; however,fluconazole may be used in milder cases. The level of side-effects may be high.
  • Prognosis: the condition is responsive to treatment in 70-75% of patients capable of a good immune response but relapses are more frequent in the immunosupressed.

  Progressive multifocal leukoencephalopathy (PML)^[16]

  PML is a progressive demyelinating condition of advanced disease caused by the John Cunningham virus (JCV) and presents with focal neurological signs, changes in personality and ataxia. The diagnosis is by MRI. There is no specific treatment and the patient usually dies within six months unless effective ART is used. Some patients develop PML during combined ART in the setting of immune reconstitution. Steroids may be useful in such cases.

  HIV encephalopathy^[17][18]

  • Presentation: HIV directly infects the nervous system and most patients dying of late-stage HIV disease have histological evidence of brain damage. Up to 10% develop cognitive, behavioural and mental abnormalities of dementia.This has been given the umbrella term HIV-associated neurocognitive disorder (HAND). In the early stages, the concentration or memory is affected, with apparentdepression and a gradual diminution of intellect. There may be increasing motor problems affecting activities of daily living. Movements may be slow. Examination may reveal inco-ordination, motor weakness, hyperreflexia and extensor plantar responses.
  • Investigations: MRI shows reduced grey matter volume in the cortex and basal ganglia. In the late stages, there is a need to differentiate from cytomegalovirus(CMV) encephalitis, which usually presents with rapidly progressive convulsion and dementia.
  • Treatment: ART has considerably improved the prognosis if given early enough. However, the virus may continue to remain, at low levels, in the body and continue to replicate, so prognosis must be guarded.

  Peripheral neuropathy and myelopathy^[13]

  This can occur at any stage of HIV infection but is more common in advanced disease. At this point, 10-15% of cases show distal symmetrical neuropathy affecting both sensory and motor systems. The condition may be exacerbated by antiretrovirals.^[19] It can cause postural hypotension, diarrhoea, impotence, impaired sweating and bladder dysfunction. HIV may directly involve the spinal cord, usually presenting with bilateral leg weakness and sensory symptoms. CMV infection presents with lumbosacral polyradiculopathy resulting in sacral paraesthesias and numbness, weakness of lower limbs and urinary retention. Treatment is mainly symptomatic with analgesics and anticonvulsants. One study in 2001 suggested the use of recombinant human nerve growth factor showed promise, although there is little subsequent supportive evidence in the literature.^[20] Another study found that capsaicin patches may be useful.^[21]

  Ocular disease

  Cytomegalovirus (CMV) retinitis^[22]

  In the absence of antiretroviral therapy, up to 30% cases of AIDS with CD4 <50/mm³show reactivation of CMV with destructive blinding retinitis. It usually presents with blurred vision, partial loss of vision in one eye, floaters or flashing lights. Typical retinal changes include irregular retinal pallor with haemorrhages in a perivascular distribution. These usually start peripherally and rapidly progress to involve the macula and whole retina, causing blindness. The main treatment is IV ganciclovirwhich is dose-limited in approximately 10% of patients by severe neutropenia andthrombocytopenia. Foscarnet is used in ganciclovir-resistant cases. The search continues for drugs which are more effective but less toxic than the current options.

  Tumours^[4]

  The incidence of both Kaposi's sarcoma and non-Hodgkin's lymphoma have been markedly reduced since the introduction of ART, although the incidence of other cancers in HIV patients has not changed.^[23][24]

  Kaposi's sarcoma

  • Presentation: this characteristically presents as multiple ecchymotic skin nodules, macules or papules. It occurs in about 15% of patients despite the advent of ART. It often affects the face early in HIV. It is also found on mucosal surfaces, usually on the hard palate. Visceral disease commonly affects the lungs and gastrointestinal tract, causing dyspnoea, cough, haemoptysis, abdominal pain or bleeding.
  • Treatment: the treatment of localised disease has been with radiotherapy, cryotherapy or intralesional vinblastine but is being superseded by pegylated liposomal doxorubicin^[25] or liposomal daunorubicin.^[26] The drugs are given intravenously and have been found to produce shrinkage of the tumour in the majority of patients.^[27]

  Non-Hodgkin's lymphoma^[28]

  This develops in 3-10% of people living with HIV, with most tumours being extranodal. Around half of these are associated with Epstein-Barr virus (EBV) infection and these are more aggressive with lower survival rates. CNS sites are common, presenting with symptoms and signs of space-occupying cerebral tumours and this carries very poor prognosis with three months' survival without ART. Tumours outside the CNS can respond to standard chemotherapy regimens.^[29] Opportunistic infections may cause death during chemotherapy.

This presents with retrosternal pain on swallowing and is usually caused by Candida albicans. This is a common complication of late-stage HIV disease. The first line of treatment is fluconazole. Other antifungal drugs tried in refractory cases include micafungin and posaconazole.

SOURCE:http://www.patient.co.uk/doctor/Complications-of-HIV-Infection.htm#