HIV INFECTION IN ADULTS

Infection/Condition and Likely Organism

Treatment

Comments

Preferred therapy

Alternative therapy

Causative organism

Cryptococcus neoformans

The incidence of cryptococcal meningitis increases as the CD4 count falls below 100 cells/ml and most cases occurs when CD4 count falls below 50 cells/ml. Mostly they present as sub-acute meningitis or meningoencephalitis with the following symptoms

• Fever.
• Malaise.
• Headache.
• Neck stiffness and photophobia (i.e. meningeal symptoms in 25-30%).
• Altered mental status/confusion, personality changes, memory loss.
• Impaired consciousness and coma.
• Focal signs, including cranial nerve palsy.

Induction phase

Cryptococcal meningitis, non CNS extrapulmonary cryptococcosis and diffuse pulmonary disease

Amphotericin B IV (0.7-1mg/kg/day)

PLUS

Flucytosine PO 25mg/kg q6h

Non CNS cryptococcosis with mild to moderate symptoms or focal pulmonary cryptococcosis:

Fluconazole: 400mg/day (800mg on day 1)

In decreasing order of efficacy

Preferred alternative:

Amphotericin B IV 0.7-1mg/kg/day

PLUS

Fluconazole 800mg/day IV or PO

Option 2 (less efficient)

5FC (Flucytosine)25mg/kg q6h

PLUS

Fluconazole 800mg/day IV or PO

Option 3 (Least efficient)

Fluconazole 1200mg/day

Amphotericin B therapy should be administered in qualified health facilities capable of close clinical and laboratory monitoring.

Dosage of Amphotericin B and Flucytosine should be adjusted to creatinine clearance rate.

Opening CSF pressure should always be measured at initiation of treatment and when lumbar puncture is performed. Repeat LP are essential to effectively manage raised intra-cranial pressure.

Corticosteroids and mannitol are ineffective to decrease intracranial pressure in Cryptococcus meningitis.

Consolidation phase 8 week

Followed by maintenance phase

Fluconazole 400mg/day (800mg on day 1)

If induction phase with Fluconazole 1200mg/ day:

Consolidation with Fluconazole 800mg/day

Maintenance Phase

At least 12 months:

Fluconazole can be stopped in patients who have been on ART and have CD4 consistently above100 cell/ mm³ for at least 6 months.

If there is fall in CD4 count, Fluconazole should be restarted again.

Fluconazole 200mg/day

Infection/Condition and Likely Organism

Treatment

Comments

Preferred therapy

Alternative therapy

Pneumocystis jirovecii (carinii*) interstitial pneumonia (PJP/PCP)

Treatment

Trimethoprim-sulfamethoxazole  15-20mg/kg/day (TMP component) IV/PO in 3 to 4 divided doses

For mild to moderate cases:

(PO₂ 70-80mmHg) Clindamycin 600mg IV/ PO q8h

PLUS

Primaquine 30mg (base) PO q24h

OR

Dapsone 100mg PO q24h

PLUS

Trimethoprim 15mg/kg/ day PO in 3-4 divided doses

For severe cases:

(PO₂ < 70mmHg) Pentamidine 4mg/kg/day IV (in 1 pint 5% dextrose or Normal saline (NS) run over 1-2 hours)

OR

Clindamycin 600mg IV q6h or 900mg IV q8h

PLUS

Primaquine 30mg (base) PO q24h

Duration 21 days

Patients with severe disease should receive corticosteroids as soon as possible (within 72 hours of starting PCP treatment).

Prednisolone dose:

40mg PO q12h for 5 days, then

40mg PO q24h for 5 days, then

20mg PO q24h for 11 days

(Total duration is 21 days)

Trimethoprim-sulfamethoxazole and Clindamycin has excellent bioavailability, may switch to PO after clinical improvement.

Patients given dapsone or primaquine should be tested for G6PD deficiency.

Prophylaxis

(Primary and secondary)

Indications:

CD4 count <200 cells/µl

CD4 count 200-250

Cells/µl if ART cannot be initiated

Trimethoprim-sulfamethoxazole  (80/400mg)

Dapsone 100mg PO q24h

OR

Aerosolized Pentamidine 300mg monthly via ultrasonic nebulizer

Discontinuation:

Can consider when CD4 100-200 cells/µL if HIV RNA is suppressed for 3-6 months with ART.

Restarting prophylaxis: CD4 count falls to <200 cells/µL or

PCP occurs at a CD4 > 200 cells/µL (lifelong prophylaxis should be considered).

Patients receiving Sulfadiazine-Pyrimethamine or Sulfadoxine-Pyrimethamine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Acute Infection

(up to 97% patients are Toxoplasma gondii IgG positive)

Trimethoprim-sulfamethoxazole 10mg/kg/day

(TMP component) IV/PO in 2 divided doses

*Pyrimethamine 200mg PO loading dose followed by Pyrimethamine:

•        50mg PO q24h (if BW≤60kg)

•        75mg PO q24h (if BW>60kg)

PLUS

Folinic acid 10-25mg IV/ PO q24h

PLUS

Clindamycin 600mg IV/ PO q6h

OR

*Sulfadiazine 1gm PO q6h

Duration: At least 6 weeks

Adjunctive corticosteroids (E.g. dexamethasone) should be administered when clinically indicated to treat mass effect associated with focal lesions or associated oedema but should be discontinued as soon as clinically feasible.

*Pyrimethamine (Sulfadoxine- Pyrimethamine) can be used interchangeably depending on availability.

Suppressive/ Maintenance

Trimethoprim-sulfamethoxazole (80/400mg) 2 tablets PO q12h

Dapsone 100mg PO q24h

OR

Clindamycin 600mg PO q8h

PLUS

Pyrimethamine 50mg PO twice-weekly

PLUS

Folinic acid 10-25mg PO twice-weekly

OR

Sulfadiazine 0.5-1gm PO q6h

PLUS

Pyrimethamine 25-50mg PO q24h

PLUS

Folinic acid 10-25mg PO q24h

Discontinuation:

Consider when CD4>200 cells/µL if HIV RNA is suppressed for 6 months with ART.

Primary Prophylaxis

Indications:

Toxoplasma gondii IgG positive with CD4<100

Trimethoprim-sulfamethoxazole (80/400mg) 2 tablets PO q24h

Dapsone 50mg PO q24h

PLUS

Pyrimethamine 50mg PO once weekly

PLUS

Folinic acid 25mg PO once weekly

OR

Dapsone 200mg PO once weekly

PLUS

Pyrimethamine 75mg PO once weekly

PLUS

Folinic Acid 25mg PO once weekly

Discontinuation:

CD4>200 cells/µL for > 3months

CD4>100 cells/µL, if HIV viral load suppressed for 3 to 6 months

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Oropharyngeal (oral thrush)

Nystatin suspension 500,000units PO 4-5 times daily

OR

Fluconazole 100mg PO q24h

*Itraconazole 200mg PO q24h

Duration: 7-14 days

Chronic suppressive therapy is usually not recommended.

*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (e.g.: Cola drinks). Avoid PPIs and H2 blockers.

Significant drug interaction with p450 enzyme inducers (e.g.: Rifampicin). Consider fluconazole if in doubt.

Oesophageal

Fluconazole 200-400mg PO/IV q24h

Itraconazole 200mg PO q24h

OR

Amphotericin B deoxycholate 0.6mg/kg IV q24h

Duration: 14-21 days

Candidiasis is the most common cause of oesophagitis with HIV infection, but CMV, HSV and aphthous ulcerations can present with similar complaints.

Endoscopy required with unusual presentations or lack of response to azole within several days.

Vulvovaginal

Refer to Obstetrics and Gynaecology Infections

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Histoplasmosis Histoplasma capsulatum

Moderate to severe disseminated disease or CNS involvement

Induction therapy *Amphotericin B deoxycholate 0.7-1.0mg/kg IV q24h for at least 2 weeks

Followed by

Maintenance therapy Itraconazole 200mg PO q8h for 3 days, then 200mg q12h for at least 12 months

*The lipid formulations of amphotericin B may be used instead if available.

All the triazole antifungals have the potential to interact with certain ARV agents and other anti-infective agents.

Mild disseminated disease (Blood culture positive but patient is asymptomatic)

Induction and maintenance therapy *Itraconazole 200mg PO q8h for 3 days, then 200mg PO q12h

For patients intolerant to Itraconazole:

Fluconazole 800mg PO q24h

OR

Voriconazole 400mg PO q12h on day 1, then 200mg PO q12h

Duration: At least 12 months

*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (e.g.: Cola drinks). Avoid PPIs and H2 blockers.

Chronic Suppressive therapy

(Secondary prophylaxis)

Indication:

Severe disseminated or CNS infection after completion of at least 12 months of treatment Relapsed despite appropriate initial therapy

*Itraconazole 200mg PO q24h

Fluconazole 400mg PO q24h

Discontinuation:

Received azole for > 1year,

AND

Negative fungal blood cultures,

AND

CD4 count > 150 cells/µL for ≥6 months on ART

Restarting secondary prophylaxis:

CD4 count < 150 cells/µL

*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (e.g. Cola drinks). Avoid PPIs and H2 blockers.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Acute infection

(Severely ill patients)

Induction therapy *Amphotericin B deoxycholate 0.6-0.7mg/kg IV for 2 weeks

Must be followed by consolidation therapy

Voriconazole 6mg/kg IV q12h on day 1, then 200mg PO q12h for at least 3 days

Must be followed by consolidation therapy.

*The lipid formulations of amphotericin B may be used instead if available.

All the triazole antifungals have the potential to interact with certain ARV agents and other anti-infective agents.

**Itraconazole:

Absorption depends on gut acidity:

Capsule: Take with food and acidic beverage (e.g.: cola drinks).

Liquid preparation: Take on empty stomach Avoid PPIs and H2 blockers.

Consolidation therapy **Itraconazole 200mg PO q12h for 10 weeks

Must be followed by maintenance therapy

Fluconazole 400mg PO q12h for 10 weeks

Must be followed by maintenance therapy

Acute infection (Mild disease)

**Itraconazole 200mg PO q12h for at least 8-12 weeks

Must be followed by maintenance therapy

Fluconazole 400mg PO q12h for at least 8-12 weeks

Must be followed by maintenance therapy

Maintenance therapy/ Secondary prophylaxis

**Itraconazole 200mg PO q24h

Fluconazole 400mg PO q24h

Discontinuation:

CD4 count>100 cells/µL for ≥6months on ART

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Mycobacterium Avium Complex (MAC) Disease

Treatment

Clarithromycin 500mg PO q12h

PLUS

Ethambutol 15mg/kg PO q24h

**PLUS

3^rd/4^th drug:

Amikacin 10-15gm/kg IV q24h

OR

Streptomycin 15mg/kg IM q24h

OR

Levofloxacin 500mg PO q24h

OR

Ciprofloxacin 500-750mg PO q12h

*Azithromycin 500mg PO q24h

PLUS

Ethambutol 15mg/kg PO q24h

**PLUS

3^rd/4^th drug:

Amikacin 10-15gm/kg IV q24h

OR

Streptomycin 15mg/kg IM q24h

OR

Levofloxacin 500mg PO q24h

OR

Ciprofloxacin 500-750mg PO q12h

Duration: At least 12 months.

* Azithromycin: use if drug interaction or intolerance precludes the use of Clarithromycin.

**Addition of 3^rd/4^th drug should be considered for patients with disseminated disease, CD4 count <50 cells/ µL or in the absence of effective ART.

Discontinuation:

Consider if patient is on ART and viral load is suppressed, CD4 > 100 cells/µL >6 months, asymptomatic or MAC, and has completed > 12 months of therapy.

Maintenance/Secondary Prophylaxis

Same as the treatment regimen

Restarting secondary prophylaxis:

CD4 < 100 cells/µL again.

Primary Prophylaxis

Indications:

CD4 < 50 cells/µL

Ruled out active MAC and TB

Azithromycin 1250mg PO once weekly

Clarithromycin 500mg PO q12h

Discontinuation:

Consider if patient is on ART

AND

Viral load is suppressed, CD4 > 100 cells/µL ≥ 3 months

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Cytomegalovirus (CMV) Disease

Treatment (CMV Retinitis) Immediate Sight Threatening Lesions (Adjacent to the Optic Nerve or Fovea)

Intravitreal injections of Ganciclovir (2mg/injection) biweekly until scarring

PLUS

Ganciclovir 5mg/kg IV q12h

OR

Valganciclovir 900mg PO q12h

Followed by maintenance

Intravitreal injections of Foscarnet (2mg/injection) biweekly until scarring

PLUS

Ganciclovir 5mg/kg IV q12h

OR

Valganciclovir 900mg PO q12h

Followed by maintenance

Duration: 14-21 days.

Immune recovery is essential for successful treatment. Start ART within 2 weeks if possible.

Treatment (CMV Retinitis)

(For Small Peripheral Lesions)

Ganciclovir 5mg/kg IV q12h

Followed by maintenance

Valganciclovir 900mg PO q12h

Followed by maintenance

Treatment (Extraocular CMV disease)

(Oesophagitis, colitis, interstitial pneumonitis, neurological disease)

Ganciclovir 5mg/kg IV q12h

Followed by maintenance

May consider switch to Valganciclovir 900mg PO q12h once patient tolerate orally

(in CMV oesophagitis and colitis only)

Followed by maintenance

Duration: 21-42 days or until signs and symptoms have been resolved.

Immune recovery is essential for successful treatment. Start ART within 2 weeks if possible.

Maintenance/ Secondary prophylaxis

(CD3 <100 cells/µL)

Ganciclovir 5mg/kg IV q24h 5-7 times weekly

Valganciclovir 900mg PO q24h

Discontinuation:

Consider if patient is on ART and viral load well suppressed, CD4 > 100 cells/µL ≥ 3 months after 3-6 months of CMV treatment.

Maintenance therapy is generally not necessary; ART offers best hope for prevention of relapses.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Salmonellosis

Salmonella non-typhi

Ampicillin 2gm IV q4-6h

OR

Trimethoprim-sulfamethoxazole (80/400mg) 2 tablets PO or 2 ampoules IV q12h

Ciprofloxacin 500-750mg PO or 400mg IV q12h

OR

Ceftriaxone 2gm IV q24h

Susceptibility profile may help guide final choice.

Duration:

IF CD4≥200: 7-14 days. If CD4<200 and with bacteraemia: 6 weeks.

Longer course with debridement and drainage needed for persistent bacteraemia or metastatic disease.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

PML (Progressive Multifocal Leucoencephalopathy)

Polyoma virus JC virus (JCV)

No effective therapy exists

With ART, some patients improve and others stabilize. Few may deteriorate due to immune reconstitution.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Isospora belli Infection

Initial Therapy

Trimethoprim-sulfamethoxazole (160/800mg) IV/PO q6h

Pyrimethamine 50-75mg PO q24h

PLUS

Folinic acid 10-25mg PO q24h

OR

Ciprofloxacin 500mg PO q12h

Duration: 10 Days.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Cryptosporidiosis

Cryptosporidium spp.

Symptomatic treatment of dirrhoea

For severe or persistent symptoms

Nitazoxanide 500mg-1g PO q12h for 2-8 weeks

OR

Paromomycin 500 mg three times daily for one week

Effective ART (to increase CD4 > 100 cells/µL) can result in complete, sustained clinical, microbiological and histologic resolution.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Microsporidiosis

Microsporidium spp.

Albendazole 400mg PO q12h for 2-4 weeks

PLUS

Symptomatic treatment of diarrhea (The best treatment option is ART and fluid support)

Effective ART (to increase CD4 > 100 cells/µL) can result in complete, sustained clinical, microbiological and histologic resolution.

Infection/Condition and Likely Organism

Suggested Treatment

Comments

Preferred

Alternative

Bartonellosis (Bartonella henselae)

For Bacillary Angiomatosis, Peliosis hepatis, Bacteraemia, and Osteomyelitis

Doxycycline 100mg PO q12h

OR

Erythromycin 500mg PO/ IV q6h

Azithromycin 500mg PO q24h

OR

Clarithromycin 500mg PO q12h

Duration: At least 3 months.

If relapse occurs after initial (>3 month) Course of therapy, long-term suppression with Doxycycline or a macrolide is recommended as long as CD4 < 200 cells/µL.

Other Severe Infection (or CNS involvement)

Doxycycline 100mg PO/ IV q12h

PLUS*

Rifampicin 300mg PO/IV q12h

OR

Erythromycin 500mg PO/ IV q6h

PLUS*

Rifampicin 300mg PO/IV q12h