INFECTIOUS DISEASES

HIV Infection – Opportunistic Infections

Fifth years

1
 Opportunistic infections
•Advances in the treatment of HIV infection with antiretroviral
therapy have led to dramatic reductions in opportunistic
infections(OIs) and death.
•Since the advent of the era of highly active antiretroviral
therapy (HAART) the incidence of ‘classic’ opportunistic
infections such as Pneumocystis jirovecii and Mycobacterium
avium complex has dramatically fallen.
 Fungal infections
P. jiroveci pneumonia
•Causative organism: Pneumocystis jiroveci
•Respiratory tract infection.
Clinical features
•Insidious onset of a non-productive cough
•Shortness of breath on exertion
•Inability to take a deep breath
•Fever
•Anorexia
•Weight loss
Diagnosis
•Demonstration of organism by immunofluorescence or silver
staining, or nucleic acid amplification techniques (NAAT)
• Diagnosis supported by:
• Presence of exercise-induced oxygen desaturation
• Typical chest radiographic appearance of bilateral interstitial
shadowing
Preferred treatment:
• Cotrimoxazole for 21 days, oral for mild, i.v for moderate to
severe (120mg/kg/day) for 3 days, then 90mg/kg/day for 18
days.
Alternative treatment:
• Mild: oral trimethoprim (10 -15mg/kg/day in 2 divided doses)
+ dapsone 100mg daily.
• Moderate – to severe: clindamycin 600mg qds po/iv for
21days + primaquine 15 - 30mg od po for 21days
• Pentamidine 4mg/kg od iv for 21days may be used
(nebulisation is necessary).
• Oxygen is essential for patients with reduced respiratory
function.
• Moderate to severe P. jiroveci pneumonia ( PaO2 < 9.3kPa or
SaO2 < 92%) needs use of adjunctive corticosteroid therapy
e.g. Prednisolone 75mg daily for 5days, 50mg for 5 days, and
then 25mg for 5 days
Oropharyngeal candidiasis
• Clinically, it is usually characterised by white plaques on the
oral mucosa.
• May present as erythematous patches or angular cheilitis.
• If swallowing is difficult (dysphagia) or painful (odynophagia),
oesophageal involvement may be suspected.
Preferred treatment:
• Fluconazole 50mg od po for 7 days
Alternative treatment:
• Itraconazole 200mg od po
 Oesophageal candidiasis
• Fluconazole 100mg od po for 2 weeks
Cryptococcal meningitis
Induction therapy
•i.v amphotericin B deoxycholate (0.7mg/kg/day) +/- flucytosine
(100mg/kg/day in divided doses) for 2 weeks.
Consolidation therapy
•Fluconazole 400mg od po for 10 weeks
Secondary prophylaxis
•Fluconazole 200mg od po for life or until immune function is
restored.
• A positive CSF cryptococcal antigen is the most sensitive
diagnostic test for cryptococcal meningitis.
• The principal diagnostic test for disseminated cryptococcal
disease is serum cryptococcal antigen.
False positive serum cryptococcal antigen in occur in the
presence of:
• Rheumatoid factor
• Heterophile antibodies
• Anti – idiotypic antibodies
• Trichosporon ashii (beigelii) infection.

• A positive CSF cryptococcal antigen, Indian ink stain of CSF

or CSF cryptococcus culture confirms meningitis.
 Protozoal infections
Toxoplasmosis
•Causative organism: Toxoplasma gondii
•Central nervous system infection
Clinical features
•Headaches,
• Fever,
•Confusion,
•Seizures,
•Focal neurological symptoms and signs such as hemiparesis
or hemisensory loss, visual field deficits, dysphagia, cerebellar
syndrome.
 Diagnosis
•Computed tomography(CT scan) – appearance of ring-
enhancing lesion(s)
•Brain biopsy (definitive, but rarely done)
 preferred treatment
•Pyrimethamine (loading dose 200mg po, followed by 50mg od
po) + sulphadiazine (1-2g qds po) for 6 weeks, then lower
doses until CD4 count > 200cells/mm3.
•Folinic acid 15mg/kg is given to prevent myelosuppression
Alternative treatment
• clindamycin (600mg qds po/iv) + pyrimethamine
•Limited data on use of atovaquone (750mg bd po), co-
trimoxazole, clarithromycin and doxycycline.
Adjunctive therapy
•Steroids(for severe oedema)/anticonvulsants(for seizures).
 Cryptosporidiosis
•Causative organism: cryptosporidium parvum
•Gastrointestinal tract infection
Clinical features
•Abdominal pain
•Weight loss
•Diarrhoea
Diagnosis
•Based on stool analysis
Treatment
• Refer to lecture notes on GI infections
•Optimal treatment is to increase immunological function with
HAART
•Supportive therapy with nutrition, hydration (iv fluid
replacement) and antidiarrhoeal (antimotility) agents is
beneficial.
• No specific treatment targeting C. parvum directly
• Paromomycin 500mg qds po for 12 weeks
• Azithromycin 500mg od po for 12 weeks
• Nitazoxanide 500mg bd po for 3 days ( up to 12 weeks)
 Bacterial infections
•Recurrent bacterial pneumonia (Streptococcus pneumoniae)
and diarrhoeal illnesses (salmonella, shigella or
campylobacter) are treated as in immunocompetent individuals
Tuberculosis
•Treatment same as for immunocompetent patients
Initiating therapy for HIV in an individual receiving TB
treatment
•After 2 weeks of TB treatment if severe immunosuppression
(CD4 count < 100mm3 )
•After 2 months if CD4 count 100 – 200cells/mm3)
•On completion of TB treatment or at 6 months if CD4 count >
200cells/mm3
 Mycobacterium avium intracellulare (MAI)
•Closely related to Mycobacterium avium complex (MAC)
•Respiratory tract infection
Clinical features
•Fevers
•Weight loss
•Diarrhoea
•Hepatosplenomegaly
Diagnosis
•Based on culture of the organism(s)
Treatment
•Clarithromycin 500mg bd po + ethambutol 15mg/kg od po ±
rifabutin 300mg/day.
•Alternative agents: quinolones and amikacin
•Corticosteroids are useful for symptomatic control
 Primary prophylaxis
•Indicated for patients with CD4 count < 50mm3 who decline
HAART, or who experience HAART failure or who are receiving
chemotherapy
•Rifabutin, clarithromycin and azithromycin are all effective.
•Clarithromycin has been studied more extensively than
azithromycin and is associated with more rapid clearance of
MAC from the blood
•Azithromycin has fewer drug interactions and is better
tolerated.
•If rifabutin (usually 300mg/day) is included in the regimen a
dose adjustment is necessary if concurrently administered
with:
• Ritonavir-boosted protease inhibitor ( rifabutin 150mg 3
times/week) or
•Efavirenz ( rifabutin 450mg daily)
 Viral infections
Cytomegalovirus disease
•CMV is a herpes virus
•Common sites of disease are the retina (CMV retinitis) and
gastrointestinal tract (neurological involvement and
pneumonitis are well reported).
•Individuals with CMV retinitis present with symptoms of
blurred vision, visual field defects or ‘floaters’
•If untreated it rapidly progresses to blindness.
 Preferred treatment
•Therapeutic approach involves an initial induction therapy
( high dose therapy for 2 – 3 weeks) until retinitis is quiescent,
followed by lower dose maintenance therapy, with reinduction
if disease progression occurs.
Induction therapy
•Ganciclovir 5mg/kg iv via central line over 1 hour or
•Valganiciclovir (pro-drug) 900mg bd po
Maintenance therapy
•Ganciclovir 6mg/kg on 5days a week or valganiciclovir 900mg
od po
Common side effects
•Neutropenia, thrombocytopenia
 Alternative treatment
Foscarnet 90mg/kg bd iv
•Has less favourable toxicity profile
•Reserved for therapeutic failure with ganciclovir
•Main adverse effects: electrolyte abnormalities, nephrotoxicity,
ulceration (i.e. genital)
Cidofovir 5mg/kg per week iv
•Requires less frequent administration: 2 doses at weekly intervals
for induction and 2 week intervals for maintenance
•Main adverse effects are nephrotoxicity and metabolic disturbances
•Reduce risk of nephrotoxicity by using hydration and oral
probenecid (2g given 3h prior to infusion and1g 2 and 8 h post-
cidofovir)
•Increased risk of nephrotoxicity if co-administered with agents
excreted via the same renal tubular anion transporter e.g. tenofovir
 Cancers
•Most common malignancies associated with HIV infection are
Kaposi’s sarcoma and lymphoma.
Kaposi’s sarcoma
•Most common malignancy in HIV sero-positive individuals.
•Caused by infection with human herpes virus 8 (HHV8)
•Majority of lesions affect the skin appear as raised purple
papules.
•KS may also affect the viscera
•In some cases, no therapeutic intervention is necessary and
cosmetic camouflage may be sufficient.
•Treatment of HIV with antiretroviral therapy usually results in
improvement and even complete resolution.
 Treatment of individual lesions
•Local radiotherapy
•Intralesional vinblastine
Treatment of severe KS
•Severe KS (wide spread cutaneous disease, significant
visceral involvement) is treated with systemic chemotherapy.
• Liposomal anthracyclines (e.g. doxorubicin and daunorubicin)
and taxanes (e.g. paclitaxel and docetaxel) (mainstay of
systemic chemotherapy)

•Liposomal doxorubicin is considered first line standard of care

for KS.
•Oral etoposide is considered second line.
• No difference is apparent between PI –based and NNRTI-
based antiretroviral regimens in terms of response of KS
• Regimen presently used at UTH: Vincristine 1.4mg/m2 +
Doxorubicin 35mg/m2 at 1 – 3 week intervals for a maximum
of 6 cycles