HIV infection and AIDS | MSF Medical Guidelines

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Last updated: January 2024

Acquired immune deficiency syndrome (AIDS) is the most advanced stage of infection with human immunodeficiency virus (HIV).

Two subtypes of HIV have been identified. HIV-1 is more widespread than HIV-2, the latter mainly being found in West Africa. HIV-2 is less virulent and less transmissible than HIV-1.

HIV weakens the immune system by causing a deficit in CD4 T lymphocytes.

Evolution of the disease

Primary infection or acute retroviral syndrome: 50 to 70% of newly infected individuals develop during seroconversion (from 15 days to 3 months post exposure), a viral syndrome with fever, malaise, and lymphadenopathy.
Asymptomatic HIV infection (after seroconversion): a period of clinical latency, but not viral latency. The time period for progression from HIV infection to the development of severe immune deficiency in western countries is approximately 10 years. This period appears to be shorter in developing countries.
Symptomatic HIV infection: with progressive destruction of the immune system, common and more severe diseases occur more frequently, and with higher mortality, in seropositive individuals.
AIDS: this stage corresponds to the development of severe opportunistic infections and neoplasms. From a biological point of view, AIDS is defined as a CD4 count < 200 cells/mm³. Without treatment the disease progresses rapidly towards death.

The World Health Organization (WHO) has proposed a clinical classification of HIV infection in 4 stages of severity for adults and adolescents and for children. [1] Citation 1. World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification de HIV-related disease in adults and children, 2007.
http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf [Accessed 17 May 2018]

Laboratory

Diagnosis of HIV infection

The diagnosis is made with serological (detection of antibodies against the virus) or virological (especially in infants) testing.
Testing should always be done voluntarily with informed consent.
All HIV test results must be strictly confidential in order to avoid discrimination.
The individual should have access to services offering pre-test and post-test counselling, treatment and support.
A diagnosis of HIV infection can be made only after at least 2 different test results (2 different brands) are clearly positive: the positive result of an initial (highly sensitive) test must be confirmed through use of a second (highly specific) test. In areas where HIV prevalence is low, diagnosis is confirmed after 3 positive test results.

CD4 lymphocyte counts

CD4 cell depletion is a marker of the progression of immune depression. The level of the CD4 cell count is a predictor of the development of opportunistic infections or neoplasms and can be used to orient their diagnosis, e.g. cerebral toxoplasmosis or cryptococcal meningitis appear when the CD4 count is below 100 cells/mm³ in adults. If clinical symptoms/signs are present suggesting one of these infections, but the CD4 count is greater than or equal to 200 cells/mm³, it is unlikely that that particular infection is present.

Opportunistic infections

It is important to screen for serious opportunistic infections in those at risk (e.g. testing for cryptococcal antigen for all adults with a CD4 count < 100 cells/mm³ regardless of symptoms).

Treatment of HIV infection

Antiretroviral (ARV) treatment a Citation a. For more information: The use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, second edition, 2016.
http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=1

A multi-drug (at least 3) antiretroviral therapy (ART) is the reference treatment. It does not eradicate the virus, but slows the progression of the disease and improves the patient’s clinical state by reducing viral replication and consequently increasing the CD4 cell count to levels beyond the threshold of opportunistic infections.

Therapeutic classes

Four major classes ARV are used:

NRTI (nucleoside/nucleotide reverse transcriptase inhibitors): zidovudine (AZT), lamivudine (3TC), abacavir (ABC), tenofovir (TDF), emtricitabine (FTC).
NNRTI (non-nucleoside reverse transcriptase inhibitors): efavirenz (EFV), nevirapine (NVP), etravirine (ETR). HIV-2 is naturally resistant to NNRTIs.
PI (protease inhibitors): atazanavir (ATV), lopinavir (LPV), ritonavir (RTV), darunavir (DRV).
INI (integrase inhibitors): dolutegravir, raltegravir.

Principles of ARV treatment

Daily triple therapy must be taken for life to prevent the rapid development of resistance. It is important that the patient understands this and that adherence to treatment is optimal.
Follow the ART protocols recommended by national HIV program.
The most widely used and easiest regimens to administer are 2 NRTI + 1 NNRTI: e.g. TDF/3TC/EFV.
In the event of treatment failure, all 3 drugs should be replaced with a second-line regimen: 2 other NRTIs + 1 PI.

Other possible combinations exist which are less commonly used or more difficult to manage.

Criteria for ARV treatment

As a priority ART should be initiated in all patients with WHO clinical stage 3 or 4 and patients with CD4 < 350 /mm³. However, those with higher CD4 counts can initiate ART.

Monitoring of ARV treatment

HIV viral load is an essential tool for monitoring the effectiveness of ARV. CD4 count is useful for identifying severely immunosuppressed. Other tests such as blood count, tests for liver (ALAT) and renal function (creatinine clearance) are not essential, but can be useful in detecting adverse effects.

Treatment of opportunistic and other infections

With progressive immunosuppression, HIV-infected patients who are not receiving triple therapy (or patients on ART but with poor adherence) become increasingly susceptible to infections. For conditions of clinical stages 2 and 3, standard treatments are usually effective. Patients may benefit from primary prophylaxis against opportunistic infections (see Primary prophylaxis). Tuberculosis (TB) is the most common serious opportunistic infection. It can be difficult to diagnose in HIV-infected patients however.

Treatment of pain

Treat all patients for associated pain (see Pain, Chapter 1).

Prevention of HIV infection

Sexual transmission

The most reliable method of prevention is the use of male or female condoms.
Male circumcision decreases significantly the risk of HIV transmission.
Early diagnosis and treatment of sexually transmitted infections is essential as they increase the transmission of HIV (see Chapter 9).
ART to HIV positive and adherent partner does protect the negative partner from HIV infection.

Occupational transmission

(accidental needle stick injuries or injuries with contaminated objects, contact between a patient’s blood and unprotected broken skin or mucous membranes)

Prevention is based on use of standard precautions to avoid contamination with soiled material or potentially infected body fluids.
Post-exposure prophylaxis (PEP): e.g. in the event of rape or occupational accidental exposure to blood, ARV treatment initiated as soon as possible within 72 hours of exposure for a duration of 1 month may reduce the risk of infection.

Nosocomial transmission

Prevention of nosocomial HIV infection is based on the rational use of injections and strict respect for hygiene and sterilization and disinfection procedures for medical material.
For transfusion: strict respect of indications for transfusion and systematic serological screening of the donor’s blood are the two indispensable precautions in the prevention of HIV transmission through transfusions.

Transmission in injection drug users

Needle and syringe exchange programs with disposable needles and syringes for users can reduce the risk.

Mother-to-child transmission (MTCT)

The global rate of vertical transmission varies from 20 to 40%. The risk of transmission through breast-feeding is evaluated at approximately 12% and persists for the duration of breast-feeding.

In pregnant women: HIV transmission from mother-to-child may be reduced by ART. The protocol called Option B+ is the internationally preferred protocol. All HIV-infected pregnant women receive lifelong triple-drug therapy, regardless of the CD4 count or clinical stage, both for their own health and to prevent transmission to the child. The most commonly recommended ART is TDF/3TC/EFV or TDF/FTC/EFV. Check national recommendations. In addition, ARVs are administered to the newborn.
Programs targeting pregnant women also include other preventive measures such as avoiding artificial rupture of the membranes and systematic episiotomy.
In breast-feeding women: exclusive breast-feeding for the first 6 months of life, introduction of complementary (solid) foods at 6 months, gradual cessation of breast-feeding to the age of 12 months.

Prevention of opportunistic infections

In the absence of ARV treatment, all HIV-infected individuals become symptomatic and evolve towards AIDS. However, some opportunistic infections can be prevented.

Primary prophylaxis

For HIV infected patients who have not previously contracted an opportunistic infection, in order to prevent the development of some opportunistic infections.

Infections	Primary prophylaxis
Pneumocystosis Cerebral toxoplasmosis Isosporiasis Various bacterial infections Malaria	co-trimoxazole PO Children: 50 mg SMX + 10 mg TMP/kg once daily Adults: 800 mg SMX + 160 mg TMP once daily

Secondary prophylaxis

For patients who develop a specific opportunistic infection, in order to prevent recurrence once treatment for the infection is completed.

Infections	Secondary prophylaxis	Comments
Pneumocystosis	co-trimoxazole PO Children: 50 mg SMX + 10 mg TMP/kg once daily Adults: 800 mg SMX + 160 mg TMP once daily	Alternative dapsone PO Children: 2 mg/kg once daily (max. 100 mg daily) Adults: 100 mg once daily
Toxoplasmosis		Alternative Adults: dapsone PO: 200 mg once weekly or 50 mg once daily + pyrimethamine PO: 75 mg once weekly + folinic acid PO: 25 to 30 mg once weekly
Isosporiasis		–
Penicilliosis Histoplasmosis	itraconazole PO Adults: 200 mg once daily	–
Cryptococcal meningitis	fluconazole PO Children: 6 mg/kg once daily Adults: 200 mg once daily	–
Oral or oesophageal candidiasis	fluconazole PO Children: 3 to 6 mg/kg once daily Adults: 100 to 200 mg once daily	Only for frequent and severe recurrences
Herpes simplex	aciclovir PO Children under 2 years: 200 mg 2 times daily Children 2 years and over and adults: 400 mg 2 times daily	Only for frequent and severe recurrences

Symptoms	Definitions and aetiologies	Diagnosis	Treatment
Diarrhoea with or without blood (also see Chapter 3)	Diarrhoea is defined as at least 3 liquid stools per day. Aetiologies: Parasitic infections • Isospora belli • Cryptosporidium • Microsporidium • Giardia lamblia • Entamoeba histolytica Bacterial infections • Shigella • Salmonella enteritis • Campylobacter enteritis Mycobacterial infections • Mycobacterium tuberculosis (gastrointestinal TB) • Mycobacterium avium complex Helminthiasis • Strongyloides stercoralis Viral infections • Cytomegalovirus (CMV) Other causes • Kaposi sarcoma • Lymphoma • Idiopathic (HIV infection) • Antiretrovirals (especially lopinavir and ritonavir)	1. History and clinical examination 2. Microscopic examination of stool for ova and parasites (2 to 3 samples) Note: I. belli, Cryptosporidium, Microsporidium, MAC and CMV are unlikely if CD4 count > 200 cells.	• Persistent (> 2 weeks) or chronic (> 4 weeks) diarrhoea is often associated with weight loss and dehydration. • Prevention or treatment of dehydration is critical (Dehydration, Chapter 1). • Depending on the results of the stool examinations: give appropriate treatment. • If there is no laboratory support: *Acute bloody diarrhoea* • First-line treatment: Children: azithromycin PO: 20 mg/kg once daily for 5 days or ciprofloxacin PO: 15 mg/kg 2 times daily for 7 days Adults: ciprofloxacin PO: 500 mg 2 times daily for 7 days • If amoebiasis suspected: tinidazole or metronidazole PO (Amoebiasis, Chapter 3). *Non-bloody persistent or chronic diarrhea* Persistent or chronic diarrhoea suggests advanced immunocompromised state. For patients who qualify for ARVs by CD4 count (or unknown CD4 count), ARV initiation is urgent and will usually resolve symptoms in 14 to 28 days. • Isospora belli: co-trimoxazole PO Children: 40 mg SMX + 8 mg TMP/kg 2 times daily for 10 days then 25 mg SMX + 5 mg TMP/kg 2 times daily for 3 weeks Adults: 800 mg SMX + 160 mg TMP 2 times daily for 7 to 10 days then 400 mg SMX + 80 mg TMP 2 times daily for 3 weeks • Cryptosporidium: no specific treatment in HIV-infected patients • Microsporidium: albendazole PO (limited efficacy) Children: 10 mg/kg 2 times daily (max. 800 mg daily) for 7 days Adults: 400 mg 2 times daily for 2 to 4 weeks • Helminthiasis: albendazole PO for 3 days Children > 6 months but ≤ 10 kg: 200 mg once daily Children > 6 months and adults: 400 mg once daily • Giardiasis: tinidazole or metronidazole (Intestinal protozoan infections, Chapter 6). • If no improvement (and no contra-indications such as bloody diarrhoea), symptomatic treatment with loperamide PO: Adults: initial dose 4 mg then 2 mg after each liquid stool (max. 16 mg daily) Nutrition ++++ Children: continue to breastfeed; increase daily calorie intake: 6-11 months: add 150 kcal daily 12-23 months: add 200 kcal daily 2-5 years: add 250 kcal daily 6-9 years: add 350 kcal daily 10-14 years: add 400 kcal daily Eliminate fresh milk, give porridge prepared with rice water or soup or yoghurts. Give 2.5 ml of oil per meal. Any child 0-5 years should receive zinc sulfate (Acute diarrhoea, Chapter 3). Adults: increase the calorie and protein intake (at least 2 g protein/kg daily). No food is excluded but avoid raw food, fresh milk and foods high in fibre. Encourage small, frequent meals.
Oral and oesophageal lesions	Fungal infections • Oral candidiasis: see Stomatitis, Chapter 3. • Oesophageal candidiasis: pain on swallowing, dysphagia. May result in weight loss. Viral infections • Oral hairy leukoplakia (keratosis on the lateral sides of the tongue due to the Epstein-Barr virus) • Oral and oesophageal herpes Aphthous ulcers	Clinical examination is enough to make a diagnosis. Consider all severe oral candidiasis (if the pharynx is involved) as oesophageal candidiasis even in the absence of dysphagia.	• Mild oral candidiasis nystatin PO Children and adults: 100 000 IU (= 1 ml) 4 times daily or miconazole oral gel Children 6 months-2 years: 1.25 ml 4 times daily Children over 2 years and adults: 2.5 ml 4 times daily The treatment lasts 7 to 14 days. • Moderate to severe oral candidiasis and oesophageal candidiasis fluconazole PO Children: 3 to 6 mg/kg once daily Adults: 50 to 200 mg once daily up to 400 mg daily if necessary The treatment lasts 7 to 14 days for oral candidiasis and 14 to 21 days for oesophageal candidiasis. Candidiasis is an indication for prophylaxis with co-trimoxazole. • Oral hairy leukoplakia: no treatment • Oral herpes: Analgesics (paracetamol, ibuprofen). For recurrent or extensive forms affecting the oesophagus, add: aciclovir PO for 7 days Children under 2 years: 200 mg 5 times daily Children 2 years and over and adults: 400 mg 5 times daily Secondary prophylaxis only for patients with frequent recurrences.
Respiratory problems (also see Chapter 2)	Cough and/or thoracic pain and/or dyspnoea in a symptomatic HIV infected patient. Aetiologies: Bacterial infections • Streptococcus pneumoniae • Haemophilus influenzae • Staphylococcus aureus Mycobacterial infections • M. tuberculosis, MAC Protozoal infections • Pneumocystis jiroveci (PCP) Fungal infections • Cryptococcus neoformans • Histoplasma capsulatum • Coccidioides immitis • Aspergillus spp • Penicillium marneffei Viral infections • CMV Neoplasms • Kaposi sarcoma • Non-Hodgkin’s lymphoma Others • Lymphoid interstitial pneumonia • Pleural effusion (often TB) • Pericardial effusion (often TB) • Pneumothorax (may be due to PCP)	1. History and clinical examination: Blood in the sputum? If fever < 7 days, dyspnoea: unlikely TB. If cough > 21 days, weight loss, thoracic pain > 15 days, no dyspnoea: likely TB. Pulmonary auscultation: bilateral lobar pneumonia? 2. If possible: a) Look for AFB in sputum b) Chest x-ray • PCP: bilateral interstitial infiltrates • TB: miliary shadowing, large heart, pleural effusion, enlarged lymph nodes inside the chest. Notes • MAC, PCP, CMV and fungal infections are unlikely in patients with a CD4 count > 200 cells/mm³. • Staphylococcal pneumonia is often associated with a pyomyositis or an abscess.	• For the diagnosis and treatment of upper respiratory tract infections, particularly pneumonia: see Chapter 2. • If the chest x-ray is consistent with staphylococcal pneumonia: Children: see Staphylococcal pneumonia, Chapter 2. Adults: ceftriaxone IM or slow IV 1 g once daily + cloxacillin IV 2 g every 6 hours • If the sputum examination is AFB+, treat for TB. • If the sputum examination is negative and the chest x-ray is consistent with PCP: co-trimoxazole PO for 21 days Children: 50 mg SMX + 10 mg TMP/kg 2 times daily Adults: 1600 SMX + 320 TMP 3 times daily Note: the symptoms may become worse during the first phase of treatment, effectiveness can only be evaluated after one week of treatment. Add prednisolone PO for patients with severe PCP with hypoxia: Children: start with 2 mg/kg daily then decrease the dose following the adult example Adults: 40 mg 2 times daily for 5 days, then 40 mg once daily for 5 days then 20 mg once daily for 10 days Secondary prophylaxis is recommended. • Fungal infections (cryptococcosis, penicilliosis, histoplasmosis): Adults: amphotericin B IV: 0.7 to 1 mg/kg once daily for 2 weeks (cryptococcosis, penicilliosis) or 1 to 2 weeks (histoplasmosis), then: fluconazole PO: 400 mg daily for 8 weeks (cryptococcosis) itraconazole PO: 200 mg 2 times daily for 10 weeks (penicilliosis) itraconazole PO: 200 mg 3 times daily for 3 days then 200 to 400 mg daily for 12 weeks (histoplasmosis) Secondary prophylaxis is recommended.
Lymphadenopathy	Enlarged lymph nodes in a symptomatic HIV-infected patient Persistent generalised lymphadenopathy (PGL): • 2 or more extra-inguinal sites • lymph nodes > 1.5 cm • enlarged for 3 or more months PGL is usually due to HIV infection. Aetiologies: HIV infection Infections • TB • Syphilis • Histoplasmosis • Toxoplasmosis • CMV Neoplasms • Kaposi sarcoma • Lymphoma	1. Clinical examination: look for a local cause (skin or dental infection etc.); TB or syphilis. 2. Suspected TB: lymph node aspiration, look for AFB, chest x-ray Note: in HIV infected patients, TB is often extrapulmonary. 3. Suspected syphilis: serology 4. If all examinations are negative: biopsy is useful to exclude lymphoma, Kaposi’s sarcoma and fungal or mycobacterial infections (see notes for patients in stage 1).	• Treat according to the aetiology or empirical treatment with, for example doxycycline PO. • TB: see the guide Tuberculosis, MSF. • Early syphilis: benzathine benzylpenicillin IM Adults: 2.4 MIU single dose (1.2 MIU in each buttock) or, if not available: azithromycin PO Adults: 2 g single dose Note: in patients in stage 1, no further investigation (other than 1, 2 and 3 in this table) or treatment are required.
Skin lesions (also see Chapter 4)	Bacterial infections • Furunculosis • Impetigo and pyoderma • Axillary hidradenitis • Pyomyositis • Syphilis Viral infections • Herpes zoster • Herpes simplex • Genital warts • Molluscum contagiosum Fungal infections • Candidiasis, dermatophytoses and deep mycoses (penicilliosis, cryptococcosis, histoplasmosis, etc.) Neoplasms • Kaposi sarcoma Other skin infections • Chronic prurigo or urticaria • Severe seborrhoeic dermatitis • Psoriasis • Scabies • Diffuse cutaneous xerosis Rash caused by medication Bed sores		Bacterial infections • Furunculosis, impetigo, chronic folliculitis: see Bacterial skin infections, Chapter 4. • Suppurative axillary hidradenitis: local treatment + doxycycline PO: 200 mg once daily for 6 weeks (in adults) • Pyomyositis: antibiotics and surgical drainage, see Pyomyositis, Chapter 10. • Primary and secondary syphilis: see Genital ulcers, Chapter 9. Viral infections • Herpes zoster: see Herpes simplex and herpes zoster, Chapter 4. For necrotic, extensive forms, eruption on the face, ophthalmic zoster, add aciclovir within 48 hours of the onset of lesions: Children (IV route): 5 to 10 mg/kg every 8 hours for 7 days Adults (oral route): 800 mg 5 times daily for 7 days • Herpes simplex: see Herpes simplex and herpes zoster, Chapter 4. • Genital warts: see Venereal warts, Chapter 9. Fungal infections • Candidiasis: 2% miconazole cream, one application 2 times daily • Dermatophytoses: see Superficial fungal infections, Chapter 4. Treatment of Kaposi sarcoma (KS) • Start promptly ART. • KS tumours with oedema or ulceration or presence of extensive oral or gastrointestinal or pulmonary KS +/- systemic illness: chemotherapy Other skin infections • Prurigo, urticaria: see Other skin disorders, Chapter 4. • Seborrhoeic dermatitis: Whitfield’s ointment or 2% miconazole, one application 2 times daily. For severe inflammation, use a topical corticosteroid in combination with miconazole. • Xerosis: zinc oxide ointment or calamine lotion • Psoriasis: corticosteroids and zinc oxide ointment • Scabies: local treatment. For crusted or profuse scabies, add ivermectin PO (see Scabies, Chapter 4).
Neurological disorders in adults	Aetiologies: Infections • TB meningitis • Cryptococcal meningitis • Cerebral toxoplasmosis • Neurosyphilis • CMV encephalitis • HIV encephalopathy • Progressive multifocal leuko- encephalopathy • Cerebral malaria Neoplasms • Primary CNS lymphoma Common causes of headache unrelated to HIV infection: sometimes more frequent in HIV infected patients (sinusitis, problems with accommodation etc.) Adverse effects of ARVs	History and clinical examination: • Change in mental state • Focal deficits • Seizures • Signs of meningeal irritation • Raised intercranial pressure • Motor problems, ataxia In settings where cryptococcal infection is common, screen all adults with CD4 < 100 prior to initiation of ART, using a rapid CrAg test on serum or plasma. In endemic areas: check for malaria (if febrile). Lumbar puncture (LP) if not contra-indicated. Elements in favour of neurosyphilis: • VDRL positive in blood and/or CSF • cells in the CSF • high protein in the CSF	Positive malaria test: see Malaria, Chapter 6. If focal signs, treat for toxoplasmosis: co-trimoxazole PO: 25 mg SMX + 5 mg TMP/kg 2 times daily for 4 to 6 weeks or pyrimethamine PO: 100 mg morning and evening on D1, then 75 to 100 mg daily + sulfadiazine PO: 2 g 2 to 3 times daily + folinic acid PO: 15 mg once daily, for 6 weeks A secondary prophylaxis is recommended. If the LP is positive: • Bacterial meningitis: see Chapter 7. • TB meningitis: see the guide Tuberculosis, MSF. • Cryptococcal meningitis [2] Citation 2. Word Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, Geneva, 2018. http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1 [Accessed 17 May 2018] : amphotericin B IV: 1 mg/kg once daily + flucytosine PO: 25 mg/kg 4 times daily for 1 week then fluconazole PO: 1200 mg once daily for 1 week then 800 mg once daily for 8 weeks or, if not available amphotericin B IV: 1 mg/kg once daily + fluconazole PO: 1200 mg once daily for 2 weeks then fluconazole PO alone: 800 mg once daily for 8 weeks or fluconazole PO: 1200 mg once daily + flucytosine PO: 25 mg/kg 4 times daily for 2 weeks then fluconazole PO alone: 800 mg once daily for 8 weeks During the induction phase: give fluconazole IV (same doses) if the patient cannot take oral treatment; liposomal amphotericin B (3 mg/kg daily 2 weeks) may be used instead of conventional amphotericin B in case of renal impairment. A secondary prophylaxis is recommended. Note: intracranial pressure (ICP) is often raised in cryptococcal meningitis. To lower ICP, repeated ‘therapeutic’ punctures to drain CSF may be necessary at the beginning of treatment. Neurosyphilis: benzylpenicillin IV: 2 to 4 MIU (1.2 to 2.4 g) every 4 hours for 14 days or ceftriaxone IV or IM: 2 g once daily for 10 to 14 days Headache of unknown origin: symptomatic treatment starting with a step 1 analgesic (see Pain, Chapter 1).
Neurological disorders in children	Aetiologies: • Bacterial meningitis • TB meningitis • Cryptococcal meningitis • Cerebral toxoplasmosis • CMV meningo-encephalitis • Cerebral malaria	Good history taking as only patients with acute episodes benefit from specific aetiological treatment (seizures, meningeal syndrome, focal signs). In endemic areas, check for malaria (if febrile). Lumbar puncture (LP) if not contra-indicated.	Positive malaria test: see Malaria, Chapter 6. If LP is not possible: • Treat for bacterial meningitis if patient febrile and/or meningeal syndrome (see Chapter 7). • If focal signs, treat for toxoplasmosis: co-trimoxazole PO: 25 mg SMX + 5 mg TMP/kg 2 times daily for 4 to 6 weeks or pyrimethamine PO: 1 mg/kg 2 times daily for 2 days then 1 mg/kg once daily + sulfadiazine PO: 40 mg/kg 2 times daily + folinic acid PO: 10 mg once daily, for 8 weeks A secondary prophylaxis is recommended. If the LP is positive: • Bacterial meningitis: see Chapter 7. • TB meningitis: see the guide Tuberculosis, MSF. • Cryptococcal meningitis (in order of preference) [2] Citation 2. Word Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, Geneva, 2018. http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1 [Accessed 17 May 2018] : amphotericin B IV: 1 mg/kg once daily + flucytosine PO: 25 mg/kg 4 times daily for 1 week then fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) for 1 week then 6-12 mg/kg once daily (max. 800 mg daily) for 8 weeks or, if not available amphotericin B IV: 1 mg/kg once daily + fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) for 2 weeks then fluconazole PO alone: 6-12 mg/kg once daily for 8 weeks (max. 800 mg daily) or fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) + flucytosine PO: 25 mg/kg 4 times daily for 2 weeks then fluconazole PO alone: 6-12 mg/kg once daily (max. 800 mg daily) for 8 weeks During the induction phase: give fluconazole IV (same doses) if the child cannot take oral treatment; liposomal amphotericin B (3 mg/kg daily, 2 weeks) may be used instead of conventional amphotericin B in case of renal impairment. A secondary prophylaxis is recommended.
Persistent or recurrent fever	Temperature > 38 °C, chronic (lasting more than 5 days) or recurrent (multiple episodes in a period of more than 5 days) Aetiologies: Infections • Common childhood diseases • Severe bacterial infections (TB, pneumonia, typhoid fever, septicaemia, meningitis, endocarditis, etc.) • Occult bacterial infections (sinusitis, otitis, urinary tract infections) • Opportunistic infections (TB, mycosis, toxoplasmosis) • Malaria Neoplasms • Non-Hodgkin’s lymphoma HIV infection Fever caused by medication	1. History and clinical examination: look for a ENT or urinary infection, TB, skin infection, enlarged lymph nodes etc. 2. In endemic areas, check for malaria. 3. Suspected TB: look for AFB. 4. Chest x-ray, CBC, blood cultures, urinalysis, stool culture, serology, lumbar puncture (LP). If the child is under treatment, consider adverse effects of medication.	Positive malaria test: see Malaria, Chapter 6. If testing is not available: in endemic areas, treat malaria. Suspected meningitis: treat according to the results of the LP. If LP is not available, treat for bacterial meningitis, see Chapter 7. Identified or suspected focus of infection: • ENT: see Chapter 2; urinary: see Chapter 9, etc. • TB: see the guide Tuberculosis, MSF.

Symptoms

Definitions and aetiologies

Diagnosis

Treatment

Diarrhoea
with or without blood

(also see
Chapter 3)

Diarrhoea is defined as at least 3 liquid stools per day.

Aetiologies:

Parasitic infections
• Isospora belli
• Cryptosporidium
• Microsporidium
• Giardia lamblia
• Entamoeba histolytica

Bacterial infections
• Shigella
• Salmonella enteritis
• Campylobacter enteritis

Mycobacterial infections
• Mycobacterium tuberculosis (gastrointestinal TB)
• Mycobacterium avium complex

Helminthiasis
• Strongyloides stercoralis

Viral infections
• Cytomegalovirus (CMV)

Other causes
• Kaposi sarcoma
• Lymphoma
• Idiopathic (HIV infection)
• Antiretrovirals (especially lopinavir and ritonavir)

1. History and clinical examination

2. Microscopic examination of stool for ova and parasites (2 to 3 samples)

Note:
I. belli, Cryptosporidium, Microsporidium, MAC and CMV are unlikely if CD4 count > 200 cells.

• Persistent (> 2 weeks) or chronic (> 4 weeks) diarrhoea is often associated with weight loss and dehydration.
• Prevention or treatment of dehydration is critical (Dehydration, Chapter 1).
• Depending on the results of the stool examinations: give appropriate treatment.
• If there is no laboratory support:

Acute bloody diarrhoea
• First-line treatment:
Children: azithromycin PO: 20 mg/kg once daily for 5 days or ciprofloxacin PO: 15 mg/kg 2 times daily for 7 days
Adults: ciprofloxacin PO: 500 mg 2 times daily for 7 days
• If amoebiasis suspected: tinidazole or metronidazole PO (Amoebiasis, Chapter 3).

Non-bloody persistent or chronic diarrhea
Persistent or chronic diarrhoea suggests advanced immunocompromised state. For patients who qualify for ARVs by CD4 count (or unknown CD4 count), ARV initiation is urgent and will usually resolve symptoms in 14 to 28 days.
• Isospora belli: co-trimoxazole PO
Children: 40 mg SMX + 8 mg TMP/kg 2 times daily for 10 days then 25 mg SMX + 5 mg TMP/kg 2 times daily for 3 weeks
Adults: 800 mg SMX + 160 mg TMP 2 times daily for 7 to 10 days then 400 mg SMX + 80 mg TMP 2 times daily for 3 weeks
• Cryptosporidium: no specific treatment in HIV-infected patients
• Microsporidium: albendazole PO (limited efficacy)
Children: 10 mg/kg 2 times daily (max. 800 mg daily) for 7 days
Adults: 400 mg 2 times daily for 2 to 4 weeks
• Helminthiasis: albendazole PO for 3 days
Children > 6 months but ≤ 10 kg: 200 mg once daily
Children > 6 months and adults: 400 mg once daily
• Giardiasis: tinidazole or metronidazole (Intestinal protozoan infections, Chapter 6).

• If no improvement (and no contra-indications such as bloody diarrhoea), symptomatic treatment with loperamide PO:
Adults: initial dose 4 mg then 2 mg after each liquid stool (max. 16 mg daily)

Nutrition ++++
Children: continue to breastfeed; increase daily calorie intake:
6-11 months: add 150 kcal daily
12-23 months: add 200 kcal daily
2-5 years: add 250 kcal daily
6-9 years: add 350 kcal daily
10-14 years: add 400 kcal daily
Eliminate fresh milk, give porridge prepared with rice water or soup or yoghurts. Give 2.5 ml of oil per meal.
Any child 0-5 years should receive zinc sulfate (Acute diarrhoea, Chapter 3).
Adults: increase the calorie and protein intake (at least 2 g protein/kg daily). No food is excluded but avoid raw food, fresh milk and foods high in fibre. Encourage small, frequent meals.

Oral and oesophageal lesions

Fungal infections
• Oral candidiasis: see Stomatitis, Chapter 3.
• Oesophageal candidiasis: pain on swallowing, dysphagia. May result in weight loss.

Viral infections
• Oral hairy leukoplakia (keratosis on the lateral sides of the tongue due to the Epstein-Barr virus)
• Oral and oesophageal herpes

Aphthous ulcers

Clinical examination is enough to make a diagnosis.

Consider all severe oral candidiasis (if the pharynx is involved) as oesophageal candidiasis even in the absence of dysphagia.

• Mild oral candidiasis
nystatin PO
Children and adults: 100 000 IU (= 1 ml) 4 times daily
or miconazole oral gel
Children 6 months-2 years: 1.25 ml 4 times daily
Children over 2 years and adults: 2.5 ml 4 times daily
The treatment lasts 7 to 14 days.

• Moderate to severe oral candidiasis and oesophageal candidiasis
fluconazole PO
Children: 3 to 6 mg/kg once daily
Adults: 50 to 200 mg once daily
up to 400 mg daily if necessary
The treatment lasts 7 to 14 days for oral candidiasis and 14 to 21 days for oesophageal candidiasis.

Candidiasis is an indication for prophylaxis with co-trimoxazole.

• Oral hairy leukoplakia: no treatment

• Oral herpes:
Analgesics (paracetamol, ibuprofen).
For recurrent or extensive forms affecting the oesophagus, add:
aciclovir PO for 7 days
Children under 2 years: 200 mg 5 times daily
Children 2 years and over and adults: 400 mg 5 times daily
Secondary prophylaxis only for patients with frequent recurrences.

Respiratory problems

(also see
Chapter 2)

Cough and/or thoracic pain and/or dyspnoea in a symptomatic HIV infected patient.

Aetiologies:

Bacterial infections
• Streptococcus pneumoniae
• Haemophilus influenzae
• Staphylococcus aureus

Mycobacterial infections
• M. tuberculosis, MAC

Protozoal infections
• Pneumocystis jiroveci (PCP)

Fungal infections
• Cryptococcus neoformans
• Histoplasma capsulatum
• Coccidioides immitis
• Aspergillus spp
• Penicillium marneffei

Viral infections
• CMV

Neoplasms
• Kaposi sarcoma
• Non-Hodgkin’s lymphoma

Others
• Lymphoid interstitial pneumonia
• Pleural effusion (often TB)
• Pericardial effusion (often TB)
• Pneumothorax (may be due to PCP)

1. History and clinical examination:
Blood in the sputum?
If fever < 7 days, dyspnoea: unlikely TB.
If cough > 21 days, weight loss, thoracic pain > 15 days, no dyspnoea: likely TB.
Pulmonary auscultation: bilateral lobar pneumonia?

2. If possible:
a) Look for AFB in sputum
b) Chest x-ray
• PCP: bilateral interstitial infiltrates
• TB: miliary shadowing, large heart, pleural effusion, enlarged lymph nodes inside the chest.

Notes
• MAC, PCP, CMV and fungal infections are unlikely in patients with a CD4 count > 200 cells/mm³.
• Staphylococcal pneumonia is often associated with a pyomyositis or an abscess.

• For the diagnosis and treatment of upper respiratory tract infections, particularly pneumonia: see Chapter 2.

• If the chest x-ray is consistent with staphylococcal pneumonia:
Children: see Staphylococcal pneumonia, Chapter 2.
Adults: ceftriaxone IM or slow IV 1 g once daily + cloxacillin IV 2 g every 6 hours

• If the sputum examination is AFB+, treat for TB.

• If the sputum examination is negative and the chest x-ray is consistent with PCP:
co-trimoxazole PO for 21 days
Children: 50 mg SMX + 10 mg TMP/kg 2 times daily
Adults: 1600 SMX + 320 TMP 3 times daily
Note: the symptoms may become worse during the first phase of treatment, effectiveness can only be evaluated after one week of treatment.
Add prednisolone PO for patients with severe PCP with hypoxia:
Children: start with 2 mg/kg daily then decrease the dose following the adult example
Adults: 40 mg 2 times daily for 5 days, then 40 mg once daily for 5 days then 20 mg once daily for 10 days
Secondary prophylaxis is recommended.

• Fungal infections (cryptococcosis, penicilliosis, histoplasmosis):
Adults: amphotericin B IV: 0.7 to 1 mg/kg once daily for 2 weeks (cryptococcosis, penicilliosis) or 1 to 2 weeks (histoplasmosis), then:
fluconazole PO: 400 mg daily for 8 weeks (cryptococcosis)
itraconazole PO: 200 mg 2 times daily for 10 weeks (penicilliosis)
itraconazole PO: 200 mg 3 times daily for 3 days then 200 to 400 mg daily for 12 weeks (histoplasmosis)
Secondary prophylaxis is recommended.

Lymphadenopathy

Enlarged lymph nodes in a symptomatic HIV-infected patient

Persistent generalised lymphadenopathy (PGL):
• 2 or more extra-inguinal sites
• lymph nodes > 1.5 cm
• enlarged for 3 or more months PGL is usually due to HIV infection.

Aetiologies:
HIV infection

Infections
• TB
• Syphilis
• Histoplasmosis
• Toxoplasmosis
• CMV

Neoplasms
• Kaposi sarcoma
• Lymphoma

1. Clinical examination: look for a local cause (skin or dental infection etc.); TB or syphilis.

2. Suspected TB: lymph node aspiration, look for AFB, chest x-ray
Note: in HIV infected patients, TB is often extrapulmonary.

3. Suspected syphilis: serology

4. If all examinations are negative: biopsy is useful to exclude lymphoma, Kaposi’s sarcoma and fungal or mycobacterial infections (see notes for patients in stage 1).

• Treat according to the aetiology or empirical treatment with, for example doxycycline PO.

• TB: see the guide Tuberculosis, MSF.

• Early syphilis:
benzathine benzylpenicillin IM
Adults: 2.4 MIU single dose (1.2 MIU in each buttock)
or, if not available:
azithromycin PO
Adults: 2 g single dose

Note: in patients in stage 1, no further investigation (other than 1, 2 and 3 in this table) or treatment are required.

Skin lesions

(also see
Chapter 4)

Bacterial infections
• Furunculosis
• Impetigo and pyoderma
• Axillary hidradenitis
• Pyomyositis
• Syphilis

Viral infections
• Herpes zoster
• Herpes simplex
• Genital warts
• Molluscum contagiosum

Fungal infections
• Candidiasis, dermatophytoses and deep mycoses (penicilliosis, cryptococcosis, histoplasmosis, etc.)

Neoplasms
• Kaposi sarcoma

Other skin infections
• Chronic prurigo or urticaria
• Severe seborrhoeic dermatitis
• Psoriasis
• Scabies
• Diffuse cutaneous xerosis

Rash caused by medication

Bed sores

Bacterial infections
• Furunculosis, impetigo, chronic folliculitis: see Bacterial skin infections, Chapter 4.
• Suppurative axillary hidradenitis: local treatment + doxycycline PO: 200 mg once daily for 6 weeks (in adults)
• Pyomyositis: antibiotics and surgical drainage, see Pyomyositis, Chapter 10.
• Primary and secondary syphilis: see Genital ulcers, Chapter 9.

Viral infections
• Herpes zoster: see Herpes simplex and herpes zoster, Chapter 4.
For necrotic, extensive forms, eruption on the face, ophthalmic zoster, add aciclovir within 48 hours of the onset of lesions:
Children (IV route): 5 to 10 mg/kg every 8 hours for 7 days
Adults (oral route): 800 mg 5 times daily for 7 days
• Herpes simplex: see Herpes simplex and herpes zoster, Chapter 4.
• Genital warts: see Venereal warts, Chapter 9.

Fungal infections
• Candidiasis: 2% miconazole cream, one application 2 times daily
• Dermatophytoses: see Superficial fungal infections, Chapter 4.

Treatment of Kaposi sarcoma (KS)
• Start promptly ART.
• KS tumours with oedema or ulceration or presence of extensive oral or gastrointestinal or pulmonary KS +/- systemic illness: chemotherapy

Other skin infections
• Prurigo, urticaria: see Other skin disorders, Chapter 4.
• Seborrhoeic dermatitis: Whitfield’s ointment or 2% miconazole, one application 2 times daily. For severe inflammation, use a topical corticosteroid in combination with miconazole.
• Xerosis: zinc oxide ointment or calamine lotion
• Psoriasis: corticosteroids and zinc oxide ointment
• Scabies: local treatment. For crusted or profuse scabies, add ivermectin PO (see Scabies, Chapter 4).

Neurological disorders in adults

Aetiologies:

Infections
• TB meningitis
• Cryptococcal meningitis
• Cerebral toxoplasmosis
• Neurosyphilis
• CMV encephalitis
• HIV encephalopathy
• Progressive multifocal leuko- encephalopathy
• Cerebral malaria

Neoplasms
• Primary CNS lymphoma

Common causes of headache unrelated to HIV infection: sometimes more frequent in HIV infected patients (sinusitis, problems with accommodation etc.)

Adverse effects of ARVs

History and clinical examination:
• Change in mental state
• Focal deficits
• Seizures
• Signs of meningeal irritation
• Raised intercranial pressure
• Motor problems, ataxia

In settings where cryptococcal infection is common, screen all adults with CD4 < 100 prior to initiation of ART, using a rapid CrAg test on serum or plasma.

In endemic areas: check for malaria (if febrile).

Lumbar puncture (LP) if not contra-indicated.

Elements in favour of neurosyphilis:
• VDRL positive in blood and/or CSF
• cells in the CSF
• high protein in the CSF

Positive malaria test: see Malaria, Chapter 6.

If focal signs, treat for toxoplasmosis:
co-trimoxazole PO: 25 mg SMX + 5 mg TMP/kg 2 times daily for 4 to 6 weeks
or
pyrimethamine PO: 100 mg morning and evening on D1, then 75 to 100 mg daily + sulfadiazine PO: 2 g 2 to 3 times daily + folinic acid PO: 15 mg once daily, for 6 weeks
A secondary prophylaxis is recommended.

If the LP is positive:
• Bacterial meningitis: see Chapter 7.
• TB meningitis: see the guide Tuberculosis, MSF.
• Cryptococcal meningitis [2] Citation 2. Word Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, Geneva, 2018.
http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1 [Accessed 17 May 2018] :
amphotericin B IV: 1 mg/kg once daily + flucytosine PO: 25 mg/kg 4 times daily for 1 week
then fluconazole PO: 1200 mg once daily for 1 week then 800 mg once daily for 8 weeks
or, if not available
amphotericin B IV: 1 mg/kg once daily + fluconazole PO: 1200 mg once daily for 2 weeks
then fluconazole PO alone: 800 mg once daily for 8 weeks
or
fluconazole PO: 1200 mg once daily + flucytosine PO: 25 mg/kg 4 times daily for 2 weeks
then fluconazole PO alone: 800 mg once daily for 8 weeks
During the induction phase: give fluconazole IV (same doses) if the patient cannot take oral treatment; liposomal amphotericin B (3 mg/kg daily 2 weeks) may be used instead of conventional amphotericin B in case of renal impairment.
A secondary prophylaxis is recommended.
Note: intracranial pressure (ICP) is often raised in cryptococcal meningitis. To lower ICP, repeated ‘therapeutic’ punctures to drain CSF may be necessary at the beginning of treatment.

Neurosyphilis:
benzylpenicillin IV: 2 to 4 MIU (1.2 to 2.4 g) every 4 hours for 14 days
or ceftriaxone IV or IM: 2 g once daily for 10 to 14 days

Headache of unknown origin: symptomatic treatment starting with a step 1 analgesic (see Pain, Chapter 1).

Neurological disorders in children

Aetiologies:
• Bacterial meningitis
• TB meningitis
• Cryptococcal meningitis
• Cerebral toxoplasmosis
• CMV meningo-encephalitis
• Cerebral malaria

Good history taking as only patients with acute episodes benefit from specific aetiological treatment (seizures, meningeal syndrome, focal signs).

In endemic areas, check for malaria (if febrile).

Lumbar puncture (LP) if not contra-indicated.

Positive malaria test: see Malaria, Chapter 6.

If LP is not possible:
• Treat for bacterial meningitis if patient febrile and/or meningeal syndrome (see Chapter 7).
• If focal signs, treat for toxoplasmosis:
co-trimoxazole PO: 25 mg SMX + 5 mg TMP/kg 2 times daily for 4 to 6 weeks
or
pyrimethamine PO: 1 mg/kg 2 times daily for 2 days then 1 mg/kg once daily + sulfadiazine PO: 40 mg/kg 2 times daily + folinic acid PO: 10 mg once daily, for 8 weeks
A secondary prophylaxis is recommended.

If the LP is positive:
• Bacterial meningitis: see Chapter 7.
• TB meningitis: see the guide Tuberculosis, MSF.
• Cryptococcal meningitis (in order of preference) [2] Citation 2. Word Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, Geneva, 2018.
http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1 [Accessed 17 May 2018] :
amphotericin B IV: 1 mg/kg once daily + flucytosine PO: 25 mg/kg 4 times daily for 1 week then fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) for 1 week then 6-12 mg/kg once daily (max. 800 mg daily) for 8 weeks
or, if not available
amphotericin B IV: 1 mg/kg once daily + fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) for 2 weeks then fluconazole PO alone: 6-12 mg/kg once daily for 8 weeks (max. 800 mg daily)
or
fluconazole PO: 12 mg/kg once daily (max. 800 mg daily) + flucytosine PO: 25 mg/kg 4 times daily for 2 weeks then fluconazole PO alone: 6-12 mg/kg once daily (max. 800 mg daily) for 8 weeks
During the induction phase: give fluconazole IV (same doses) if the child cannot take oral treatment; liposomal amphotericin B (3 mg/kg daily, 2 weeks) may be used instead of conventional amphotericin B in case of renal impairment.
A secondary prophylaxis is recommended.

Persistent or recurrent fever

Temperature > 38 °C, chronic (lasting more than 5 days) or recurrent (multiple episodes in a period of more than 5 days)

Aetiologies:

Infections
• Common childhood diseases
• Severe bacterial infections (TB, pneumonia, typhoid fever, septicaemia, meningitis, endocarditis, etc.)
• Occult bacterial infections (sinusitis, otitis, urinary tract infections)
• Opportunistic infections (TB, mycosis, toxoplasmosis)
• Malaria

Neoplasms
• Non-Hodgkin’s lymphoma

HIV infection

Fever caused by medication

1. History and clinical examination: look for a ENT or urinary infection, TB, skin infection, enlarged lymph nodes etc.

2. In endemic areas, check for malaria.

3. Suspected TB: look for AFB.

4. Chest x-ray, CBC, blood cultures, urinalysis, stool culture, serology, lumbar puncture (LP).

If the child is under treatment, consider adverse effects of medication.

Positive malaria test: see Malaria, Chapter 6.
If testing is not available: in endemic areas, treat malaria.

Suspected meningitis: treat according to the results of the LP.
If LP is not available, treat for bacterial meningitis, see Chapter 7.

Identified or suspected focus of infection:
• ENT: see Chapter 2; urinary: see Chapter 9, etc.
• TB: see the guide Tuberculosis, MSF.

Footnotes

(a)For more information: The use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, second edition, 2016.
http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=1

References

1.World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification de HIV-related disease in adults and children, 2007.
http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf [Accessed 17 May 2018]
2. Word Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, Geneva, 2018.
http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1 [Accessed 17 May 2018]