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Diagnosis & Management:

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HIV infection


Risk assessment 

Patients presenting for HIV serology should  be assessed by a medical officer for STD and HIV risk, which requires taking a detailed sexual and blood exposure history. In addition to routine risk assessment (see Chapter 1), it is useful to determine if the patient has had a previous HIV test, and ask why the patient believes they need a test. Infection with an STD at the time of exposure increases the risk of HIV acquisition.

Therefore, all patients who are at risk of HIV should be advised of the risk of other STDs and be offered testing.

Clinical presentation

 Clinical presentations of HIV vary depending on the stage of infection, which includes the following.

Acute infection (seroconversion)

50-70% of patients experience a mononucleosis-like illness including  fever, lethargy, myalgia, arthralgia, headache, maculopapular rash, lymphadenopathy, splenomegaly  3-6 weeks after infection.

Asymptomatic infection

Following seroconversion patients may remain asymptomatic for many years.

Symptomatic infection

Persistent generalised lymphadenopathy (nodes ³ 1 cm diameter, at 2 extrainguinal sites for 3 months) occurs commonly but is not of prognostic significance.

The degree of immune suppression ( measured as the CD4 cell count) predisposes to the development of certain illnesses.

CD4 Cell Count

Common Clinical Features

150-500/mL

Oral and vaginal candidiasis, oral hairy leukoplakia, sinusitis, gingivitis, seborrheic dermatitis, psoriasis, warts, molluscum contagiosum, recurrent varicella-zoster and herpes simplex infection, cervical dysplasia, tuberculosis, fever, sweats, weight loss

< 150/mL

Pneumocystis  jiroveci pneumonia, Kaposi’s sarcoma, oesophageal candidiasis, cerebral toxoplasmosis, lymphoma, HIV dementia, cryptococcal meningitis

< 50/mL

Cytomegalovirus retinitis, cerebral lymphoma, Mycobacterium avium complex infection

Diagnosis

Pre test counselling should be performed and informed consent obtained prior to testing.  HIV testing is performed by a screening ELISA which detects both HIV p24 antigen and HIV antibodies.  A positive screening ELISA is confirmed on a Western Blot assay  If the Western Blot is negative, the ELISA result is considered to be a false positive, indicating the patient is not infected with HIV. Repeat testing is only indicated if the patient has been at risk in the three month period prior to the test.

If the Western Blot yields an indeterminate result, the patient may have been recently infected with HIV and may be in the process of seroconverting.  HIV  screening ELISA testing should be repeated at 2 weekly intervals to determine whether the Western Blot assay becomes positive .

If the Western Blot is positive, a report is returned with a “confirmed positive” statement.  These patients require specific post test counselling and appropriate medical assessment. Further  assessment should be conducted at 3-6 monthly intervals.

 

The  following table outlines the clinical features of the above infections   

Infectious agent

Diagnosis 

Clinical features

Pneumocystis jiroveci

Pneumocystis  jiroveci pneumonia 

Dry cough

Dyspnoea

Fever

Night sweats

Candida species

Oral candidiasis (thrush)

White mucosal plaques or erythema in oral cavity

 

Oesophageal candidiasis

Dysphagia 

+/- chest pain

 

Vaginal candidiasis

Vaginal discharge, erythema, itching

Herpes simplex virus (HSV)

Oral, genital and anal HSV genital and anal vesicular dermatitis

Clusters of painful vesicular lesions or shallow ulcers

Varicella zoster virus (VZV)

Shingles/Herpes zoster

Dermatomal pain

Vesicular lesions in dermatomal distribution

Mycobacterium tuberculosis

Pulmonary tuberculosis

Cough

Fever

Weight loss

Fatigue

 

Extrapulmonary tuberculosis

Enlarged lymph nodes or spleen

Cryptococcus neoformans

Cryptococcal meningitis

Headaches

Neurologic abnormalities 

+/- meningism 

+/- fever

Cytomegalovirus (CMV)

Retinitis

Visual disturbance

 

Enterocolitis

Diarrhoea

Abdominal tenderness

Bloating

Mycobacterium avium complex (MAC)

MAC bacteraemia, wasting 

Chronic or recurrent fever

Weight loss

Fatigue

Toxoplasma gondii

Toxoplasma encephalitis

Headache

Drowsiness

Fever

Focal neurologic abnormality

Seizures

Cryptosporidium

Cryptosporidial enteritis 
+/- cholangitis

Chronic diarrhoea —may resolve spontaneously in early HIV infection

Right upper quadrant pain

Microsporidia (several organisms)

Microsporidial enteritis 
+/- cholangitis

Chronic diarrhoea

May be asymptomatic

 

Malignancies

Clinical features

Kaposi’s sarcoma

Red/purple skin and mucosal lesions

Bleeding oral lesions

Gastrointestinal obstruction causing nausea/vomiting

Pulmonary disease—dyspnoea

Lymphatic system involvement—swelling of extremities

Non-Hodgkins lymphoma

Splenomegaly

Focal neurologic abnormality

Increasing asymmetrical lymphadenopathy

Primary lymphoma brain

Headache

Focal neurologic abnormality

Cervical dysplasia/cancer

Post-coital bleeding, intermenstrual bleeding

Abnormal Pap smear

Anogenital cancer

Mucosal lesion—non-healing

Abnormal biopsy

The case definition of AIDS-defining illnesses used in Australia and the United States is shown in Appendix 3.

 

Management

 Medical history 

At the first appointment after diagnosis complete assessment includes a full medical and sexual history, including current state of health and systems review.

Examination

A complete medical examination  including:

  • the patient’s weight and vital signs

  • lymphadenopathy: cervical, axillary and inguinal

  • skin lesions or rashes

  • oral lesions

  • hepatosplenomegaly

  • genital, including anorectal, lesions

  • any neurologic abnormalities

  • inspection of fundi (in patients with CD4 < 50/mL review by an ophthalmologist should be performed 3 to 6 monthly)

 Investigations

The following investigations are conducted:

 at first visit  after diagnosis

  • repeat HIV ELISA  for confirmation

  • HIV viral load

  • liver function tests (LFTs), electrolytes, renal function tests

  • amylase, CK

  • full blood examination (FBE)

  • CD4, CD8 lymphocyte markers

  • serologic tests for syphilis

  • Hepatitis A serology

  • Hepatitis B serology

  • Hepatitis C serology

  • HSV type 2, EBV, CMV, toxoplasmosis serology

  • G6PD in case future use of sulphonamides is required.

 Subsequent routine 3-6 monthly follow up 

  • FBE, CD4/CD8 lymphocyte surface markers, HIV viral load, LFTs, electrolytes, renal function tests. 

  • amylase, CK, lipase,to check for medication side effects if on HAART

  • when the CD4 count falls below 100, regular screening for MAC should be performed (Mycolytic F)

  • Pap smear should be performed 6-12 monthly, more frequently as CD4 count declines 

  • STD check should be included if relevant symptoms exist or if exposure has occurred.

Antiretroviral therapy

Combination antiretroviral therapy has been demonstrated to significantly increase life expectancy and delay the progression to AIDS in individuals with a CD4 cell count below 500/mL. As yet, there are no published data on the effect of combination therapy in individuals with early infection and a normal CD4 cell count.  

Patients are usually prescribed a minimum of three drugs to include drugs from at least two of the following categories.

Treatment recommendations are constantly changing and a detailed description of specific treatment of HIV infection is beyond the scope of these guidelines . Antiretroviral therapy should only be initiated by practitioners experienced in their use.

Currently, the main antiretroviral agents for the management of HIV infection in Australia include:

Nucleoside analogue reverse transcriptase inhibitors 

  • abacavir (Ziagen)

  • didanosine (ddI, dideoxyinosine, Videx)

  • didanosine enteric coated (ddI EC, dideoxyinosine EC, Videx EC)

  • lamivudine (3TC;)

  • stavudine (d4T, Zerit)

  • zalcitabine (ddC, dideoxycytidine, Hivid)

  • zidovudine (ZDV, AZT, Retrovir;)

  • combine formulations

  • abacavir, lamivudine, zidovudine (Tizivir) 

  • lamivudine, zidovudine (Combivir)

 

Nucleotide analogue reverse transcriptase inhibitors

  • tenofivir (Viread)

 Non-nucleoside analogue reverse transcriptase inhibitors

  • delavirdine (Rescriptor)

  • efavirenz (Stocrin)

  • nevirapine (Viramune)

 Protease inhibitors

  • atazanavir (Reyataz)

  • indinavir (Crixivan)

  • lopinavir (combined formulation with ritonavir, Kaletra)

  • Fosamprenavir (Telzir)

  • nelfinavir (Viracept)

  • ritonavir (Norvir)

  • saquinavir (Invirase – hard-gel capsule, Fortovase – soft gel capsule)

 Fusion inhibitors

  • enfurvirtide (Fuzeon)

 

Management of Opportunistic Infections 

(less likely to occur because of the efficacy of antiretroviral and preventive therapy)

Infection

Management

Pneumocystis  jiroveci

Prophylaxis
CD4 < 200/
mL

Trimethoprim-sulfamethoxazole (TMP-SMX)      
1 DS tablet (160 mg/800 mg) daily

or

Dapsone 100 mg twice weekly

or

Pentamidine 300 mg by nebuliser once a month. Nebulised salbutamol may be used as a premedication to reduce bronchospasm.

Pneumocystis  jiroveci

Acute infection

  

Intravenous therapy

if acutely ill, unable to take oral medication, or pO2<60:

Trimethoprim 20 mg/kg/day and sulfamethoxazole 75-100 mg/kg/day in 4 divided doses for 21 days

or

Pentamidine 3 mg/kg once daily

plus

Hydrocortisone 100 mg iv qid for 7 days

Oral therapy

TMP-SMX 2 DS tablets  tid for 14-21 days

or

Trimethoprim 200 mg qid and dapsone 100 mg daily for 14-21 days

plus

Prednisolone 50 mg/day orally for 7-14 days. 

Candidiasis

 

Oral
(treat until symptoms resolve)

Fluconazole 200 mg orally daily for 7 days

           or

Nystatin 100,000 unit tablet dissolved in mouth 3-5 times daily

or

Amphotericin B 10 mg lozenges orally 3-5 times daily

Vulvovaginitis

See Vulvovaginal candidiasis diagnosis and management guidelines (Chapter 10 of this book)

 

 

Oesophagitis

  

Fluconazole 200 mg orally daily for 2 weeks, then 50-100 mg daily

Long term secondary prophylaxis is recommended to prevent relapse.

Cryptococcal meningitis

Acute infection

Amphotericin B 0.6-0.8 mg/kg/day iv plus
5-flucytosine 100 mg/kg/day orally qid for 2 weeks

followed by

Fluconazole 400 mg daily for 6-10 weeks

Maintenance

Fluconazole 200 mg once daily 

There is a 60% recurrence rate if maintenance therapy is not taken.

Toxoplasma encephalitis

Acute Infection

 

Pyrimethamine 200 mg orally as a single dose then 50 mg orally daily plus folinic acid 10 mg orally daily plus sulfadiazine 1 g orally qid for 6 weeks

or

Pyrimethamine, folinic acid as above plus clindamycin 900 mg iv qid for 3 weeks, then 450 mg orally qid for 3 weeks

Maintenance

 

 

Prophylaxis

Pyrimethamine, folinic acid plus sulfadiazine 500 mg orally qid

or

Pyrimethamine, folinic acid, plus clindamycin 300 mg orally qid

TMP-SMX 1 DS tablet daily

Mycobacterium avium 
complex

Treatment

Rifabutin 300 mg orally daily, plus
Ethambutol 400 mg orally bd, plus
Clarithromycin 500 mg orally bd.

The required duration of treatment is uncertain, but should be at least 12 weeks. Indefinite maintenance therapy (with 2 agents) should continue.

 

Prophylaxis:
CD4£
100/mL

Azithromycin 1.2 g orally weekly

Herpes simplex/zoster

Severe

Aciclovir 5 mg/kg iv tds for 7 days

Moderate

Valaciclovir 1 g orally tds  for 7 days

Suppression

Valaciclovir 500 mg orally bd

Cytomegalovirus retinitis

Initial treatment

Ganciclovir 5  mg/kg iv bd for 2 weeks

or

Foscarnet 90 mg/kg iv bd for 2 weeks

Maintenance

Ganciclovir 10 mg/kg iv 3 days/week

or

Foscarnet 90 mg/kg iv 5 days/week

Cryptosporidium enteritis

 

Anti retroviral therapy with immune reconstitution controls persistent cryptosporidiosis

Paromomycin 500 mg orally tds until resolution

Bacterial pneumonia

 

Ceftriaxone 1 g iv daily for 10-14 days

followed by

Augmentin Duo 850 mg orally bd until resolution

 Prophylactic therapy against opportunistic infections