Fever and pain	aspirin and paracetamol
Antibiotics	ciprofloxacin, ofloxacine, sulfamethoxazole, clarithromycine, azitromycine
Antivirals	aciclovir, famciclovir
Mycobacteria	dapsone, ethambutol, pyrazinamide, INH
Antihistamines	cetirizine
Peptic ulcers	ranitidine
Beta-blockers	atenolol

When to perform resistance testing?

In most developing countries antiviral agents are scarcely available, if at all. Determining resistance in this context is, therefore, not very meaningful. Nevertheless, it is useful to be familiar with the underlying principles.

In the West resistance is determined:

(1) in a pregnant woman before initiating or after failure of therapy when a new treatment is being considered,

(2) upon initiating antiviral therapy in a child,

(3) after failure of therapy when a modification of the therapy is being considered. It should be considered

(4) for an as yet untreated patient before the start of therapy, especially if this is at the time of seroconversion. Viral mutants can in fact “disappear” after the acute phase (they are less easily detected) as they have a lower fitness, in the Darwinian sense of the word. If resistance is not determined in the acute phase of the disease, it is nevertheless advisable to store plasma so that such an investigation can be carried out later.

In (5) post-exposure prophylaxis an attempt should be made to get a sample from the index case.

In each case one should not wait until the results of the resistance determination are known before starting treatment.

However, when the results become available, treatment can be adjusted as necessary.

Techniques

Tests for resistance determination should be carried out with viral RNA derived from plasma, before therapy is stopped and before starting new therapy. It is only possible if there is a detectable viral load (preferably > 1000 RNA copies/ml plasma).

Genotype techniques

• Sequencing: amplification by RT-PCR and automatic sequencing. There is significant interlaboratory variability. In half of the laboratories it has been found that at least 25% of the virus population must consist of mutants before they can be detected.

• LIPA: Line Probe Assay for RT. Detects better some mixed virus populations but can miss certain mutations.

Phenotype techniques

• Virus culture: difficult and time consuming.

• Recombinant virus: the RT and Protease genes of the virus that is to be tested are integrated in a laboratory virus from which these genes have been deleted. This virus is then cultured. With this technique 25% of the virus population must also consist of mutants before any difference in sensitivity can be detected.

• Virtual phenotype: sequencing of the mutant virus and use of a software program to predict sensitivity/resistance.

Nucleoside analogue reverse transcriptase inhibitors
AZT (azidothymidine)	Zidovudine	Retrovir®
3TC (3-deoxy-thiacytidine)	Lamivudine	Epivir®
AZT + 3TC fixed combination	Zidovudine + Lamivudine	Combivir®
ddI (di-deoxy-inosine)	Didanosine	Videx®
ddC (di-deoxy-cytidine)	Zalcitabine	Hivid®
D4T	Stavudine	Zerit®
	Abacavir	Ziagen®
FTC	Emtricitabine (3TC-analogue)	Coviracil®, Emtriva®
Nucleotide reverse transcriptase inhibitor
Bis-POC-PMPA	Tenofovir	Viread®
Bis-POM-PMEA	Adefovir	Preveon®
Non-nucleoside reverse transcriptase inhibitors
Delavirdine	Rescriptor®
Nevirapine	Viramune®
Emivirine	Coactinon®
Efavirenz	Sustiva®, Stocrin®
Loviride
Protease – inhibitors
Ritonavir	Norvir®
Saquinavir	Invirase®, Fortovase®
Nelfinavir	Viracept®
Indinavir	Crixivan®
Amprenavir	Agenerase®
Lopinavir-ritonavir	Kaletra®
Integrase inhibitors
Zintevir

Product	Daily dose	Side-effects	Precautions
Efavirenz (Stocrin®) 200 mg	1 x 600 mg	Crystalluria, influenza, depression Concentration disorders	Teratogenic, Not active against HIV-2 Not with saquinavir
Delavirdine (Rescriptor®) 100 mg tablet	3 x 400 mg	Rash, Stevens-Johnson, headache	Not with antacids. Not active against HIV-2.
Nevirapine (Viramune®) 200 mg	2 x 200 mg maintenance dose	Cutaneous rash	Gradually increase dose. Begin 200 mg per day x 2 weeks Then 400 mg per day Not with saquinavir

Product	Daily dose	Side-effects	Precautions
Zidovudine (Retrovir®) Tablet 100/250/300mg	2 x 300 mg	Anaemia, leukopaenia, myalgia, nausea	Check haematology. Not together with Zerit®
Lamivudine (Epivir®) Tablet 150 mg	2 x 150 mg	Usually tolerated well; neuropathy, pancreatitis	None Not together with Hivid®
Combivir® AZT 300 + 3TC 150	2 x 1 tablet	See above	See above
Zalcitabine (Hivid®) Tablet 375 / 750 g	3 x 0,75 mg	Peripheral polyneuropathy, oral and oesophageal ulcers	None Not together with Zerit®, Videx® or Epivir®
Didanosine (Videx®) Tablet 25-50-100-150 mg Tablet 250 EC, 400 mg EC Powder 100, 167, 250 mg	If > 60 kg, then 2 x 200 mg tabl or 1 x 400 mg EC tabl or powder 2 x 250 mg	Pancreatitis, hyperuricaemia, Peripheral polyneuropathy	Take fasting, chew or dissolve tablet in water or apple juice before swallowing. Not together with Hivid®. Two hour interval with indinavir
Stavudine (Zerit®) 30/40 mg Zerit XR = once daily	2 x 30 (<> 2 x 40 (> 60 kg)	Usually tolerated well, Peripheral polyneuropathy, liver disorders	Dose according to weight and kidney function. Not together with AZT or Hivid®
Abacavir (Ziagen®) 300 mg tablet	2 x 300 mg	Flu-like syndrome, rash, dizziness, gastrointestinal and liver disorders
Adefovir (Preveon®) 60 / 120 mg tablet	4 x 120 mg	Neutropaenia, proteinuria, Gastrointestinal and liver disorders	To be taken together with L-carnitine 500 mg

Product	Daily dose	Side-effects	Precautions
Saquinavir (Invirase®) Tablet 200 mg Soft gel (Fortovase®)	3 x 600 mg or 2 x 400 mg if taken with Norvir	Tolerated relatively well; nausea, diarrhoea, headache	Taking with fat-rich meals or with grapefruit juice raises blood levels
Ritonavir (Norvir®) Tablet 100 mg Syrup 80 mg/ml	2 x 600 mg or 2 x 400 mg if taken with Invirase®	Nausea, vomiting, diarrhoea, paraesthesias, hypertriglyceridaemia. Lower dose is used as booster.	Take with meals. Gradually increase dose, store cool and in the dark, many interactions with other medicaments
Indinavir (Crixivan®) Capsule 200 / 400 mg	3 x 800 mg	Kidney stones, hyperbilirubinaemia, haemolytic anaemia	Hydration important, take on empty stomach (or with low-fat meal)
Amprenavir (Agenerase®) Capsule 150 / 600 mg	2 x 600-1200	Gastrointestinal disturbances, liver function, rash, insomnia	None
Nelfinavir (Viracept®) Tablet 250 mg Oral powder 50 mg/g	3 x 750 mg or 2 x 1250 mg	Diarrhoea	Take with meals. Not with acid drink (bitter taste).
Lopinavir (Kaletra®)	3 tablets BD	Nausea, diarrhoea

Nucleosides analogues	Inhibition of mitochondrial DNA-polymerase: Lactic acidosis (Krebs cycle in mitochondria disturbed), cardiomyopathy, peripheral neuropathy, liver steatosis, pancreatitis.
Nucleotides analogues	Renal tubular toxicity: Fanconi-like syndrome (reversible)
Non-nucleosides RT inhibitors	Hypersensitivity reactions (first 6 weeks)
Protease inhibitors	Lipodystrophy, hypertriglyceridaemie, glucose intolerance

Abacavir	Hypersensitivity reactions first 6 weeks. Fever, malaise, rash
Didanosine	Gastrointestinal intolerance, gout
Lamivudine	Anaemia, neutropaenia
Stavudine	Macrocytosis
Zalcitabine	Oral ulcers
Zidovudine	Anaemia, neutropaenia, macrocytosis
Amprenavir	Hypersensitivity reactions with rash
Indinavir	Nephrolithiasis
Nelfinavir	Diarrhoea
Ritonavir	Nausea, vomiting, dysgeusia, perioral paraesthesias, hot flushes
Saquinavir	Diarrhoea
Delaviridine	Stevens-Johnson syndrome
Efavirenz	Sleep and concentration disorders, nightmares, depression
Nevirapine	Stevens-Johnson syndrome
Hydrea	Bone marrow suppression, stomatitis, leg ulcera

Some opportunistic infections are incurable, whereas others respond well to medicinal therapy and may be prevented with prophylactic medicines. There is at present no adequate and simple treatment for cryptosporidiasis. Treatments are sometimes complex such as for infections with Mycobacterium avium.

Several treatment schemes are possible.

• 1st choice: Intravenous or oral trimethoprim/sulphamethoxazole (= cotrimoxazole, Bactrim®, Eusaprim®) 4 x 3 ampoules IV per day or 6-8 Bactrim forte® tablets per day. If there is no pronounced dyspnoea, the treatment can be given all orally. Side-effects of the medicaments occur frequently (allergic reactions with cutaneous abnormalities).

• 2nd choice: Oral dapsone/trimethoprim (Dapson® 100 mg/day + Wellcoprim® 20 mg/kg/day divided over 4 doses). With less serious PCP 100 mg dapsone is administered together with TMP (trimethoprim) 3 x 300 mg/day.

• 3rd choice: Pentamidine (Pentacarinat®) IV. The guide dose is 4 mg/kg in one administration over 8 hours in a 5% glucose infusion.

• 4th choice: Pentacarinat® in 300 mg aerosol in 6 ml sterile water. It is advised to give salbutamol puffs beforehand.

• Alternatives: other medicaments are clindamycin + primaquine, atovaquone and trimetrexate (Neutrexin®). The duration of the treatment is 21 days.

In case of severe hypoxia intravenous steroids (methylprednisolone) should be given. The patient may exhibit a hypersensitivity reaction due to the release of large quantities of antigenic material from the organisms. At later stages, corticosteroids are no longer effective.

A relapse frequently occurs after discontinuing a "curative" treatment. Prophylaxis is therefore given after the initial treatment. The same medicaments but in lower dose (Bactrim forte® 1 per day; or dapsone 100 mg/day) PO or 300 mg pentamidine-aerosol once a month can be used. Fansidar® 1 tablet per week can also be given. Cotrimoxazole acts simultaneously as a prophylactic agent for toxoplasmosis. Dapsone can be tried when cotrimoxazole is not tolerated.

This parasite is sensitive to clindamycin (Dalacin C, 4 x 600 mg per day) and to pyrimethamine (Daraprim®, 100 mg day 1, thereafter 50 mg per day) + sulphadiazine (4-6 g per day). It is best with this latter combination to add 15-30 mg folinic acid (Ledervorin®) per day to reduce bone marrow toxicity. Do not confuse folinic acid and folic acid: folic acid counteracts the therapeutic action of pyrimethamine. Pyrimethamine 50 mg together with dapsone 100 mg can also be used for toxoplasmosis. Atovaquone is moderately active against this organism. Corticosteroids are indicated when there are signs of intracranial hypertension. Phenytoin (Diphantoine®) can be used in epilepsy. Prevention of relapse with cotrimoxazole, pyrimethamine + sulphadiazine or dapsone is indicated after the attack therapy.

his is a unicellular organism that causes diarrhoea. Transmission is faeco-oral. It is sometimes quite difficult to detect in the stools. It is sensitive to trimethoprim/sulphamethoxazole (Bactrim®, Eusaprim®). If this cannot be used, pyrimethamine (Daraprim®) can be used. The combination ornidazole-albendazole can be used as third choice.

Candida albicans

in the mouth, throat and oesophagus causes difficulty in swallowing. This fungal infection can be treated with gentian violet or nystatin tablets, ketoconazole (Nizoral®), topical miconazole (Daktarin®), systemic itraconazole (Sporanox®) or fluconazole (Diflucan®). Gentian violet (1.5 ml 0.5 % aqueous solution, 2 x per day) is cheap, but stains the mouth purple. Gentian violet does not help in oesophageal candidiasis. Itraconazole and fluconazole are very expensive. Buccal tablets containing miconazole in a prolonged release formulation can be placed under the upper lip for local (topical) treatment of oropharyngeal candidiasis. Voriconazole, a new triazole, is very promising but at the moment there is very little data on it. It is also active against Candida kruseii, a yeast that is inherently resistant to fluconazole. It penetrates the blood-brain barrier and can be used in cases resistant to amphotericin B. Caspofungin (Cancidas®) belongs to the new class of echinocandins, and is active against divers Candida species (C. albicans and several C. non-albicans, including C. krusei). The normal dose is 70 mg as a single start-dose, followed by 50 mg/day IV. For patients heavier than 80 kg, a daily dose of 70 mg/day is advised. In case of medium liver failure (Child-Pughscore 7-9) 35 mg/day as maintenance dose is advised. There is no need for dose-adjustment in case of renal failure.

Cryptococcus neoformans is a yeast sensitive to amphotericin B (Fungizone®) and flucytosine (Ancotil®). Fluconazole (Diflucan®) can also be used and has the great advantage that it can be given orally. This makes prophylaxis possible, though this medication is very expensive. The cost of the medicament brings into questions whether it is worthwhile detecting cryptococcal infection in developing countries. The patient and/or his family can be ruined financially. The combination of antifungal drugs and gamma-interferon is being studied.

Blastomyces dermatitidis causes blastomycosis (USA and Middle East). The disease often resembles tuberculosis or a carcinoma. It can be treated with itraconazole (200-400 mg/day for a minimum of 6 months). Amphotericin B is used when the infection is resistant to itraconazole or when the brain is affected. There is still insufficient experience with echinocandine.

Herpes simplex can cause skin lesions and can also affect the gastrointestinal system. An oral antiviral treatment for 5 days can be considered in cases of a first episode of herpes genitalis. The antiviral agents aciclovir (Zovirax®), famciclovir (Famvir®) and valaciclovir (Zelitrex®) are all equally effective. However, the risk of recurrences is not diminished by these. Treatment must be started as soon as possible. Topical antiviral agents are not very effective. IV administration is no better than oral treatment. Local analgesics help to diminish the pain of miction or defaecation.

Dosage of antiviral agents	Aciclovir	Famciclovir	Valaciclovir
First acute episode (5 days)	200 mg 5 x p.d.	250 mg 3 x p.d.	500 mg 2 x p.d.
Treatment of recurrences (5 days)	200 mg 5 x p.d.	125 mg 2 x p.d.	500 mg 2 x p.d.
Prophylaxis of recurrences (1 year)	400 mg 2 x p.d.	250 mg 2 x p.d.	500 mg 1 x p.d.

Treatment of recurrences

Episodic antiviral treatment or a prolonged prophylactic treatment can be considered in addition to the symptomatic treatment.

• Episodic antiviral therapy must be started upon appearance of the first symptoms. The duration of the symptoms is diminished by only 1 to 2 days.

• Prophylactic therapy lasting 6 months to one year is indicated for patients who have more than 6 to 8 relapses per year. A formal diagnosis (culture, PCR) is advisable before starting it. The patient's physical and mental well being can be considerably improved with prophylactic therapy.

• In patients in an advanced stage of immunodepression, herpes infections are often very serious. The possibility of the existence of these should be clinically considered when persistent, painful antibiotic-resistant genital or perianal ulcers are present. In Belgium the prevalence of strains resistant to aciclovir is 5 to 10%. In this case foscarnet can be used as an alternative.

Treatment of herpes genitalis during pregnancy.

The purpose of the treatment is both to alleviate the symptoms of the mother and to diminish the risk of neonatal herpes. Approximately 85% of neonatal herpes cases are attributable to perinatal transmission of the virus during vaginal childbirth. The risk is particularly high when the woman develops a primo-infection during the third trimester of pregnancy. If herpetic lesions first appear during the first trimester of pregnancy treatment with aciclovir can be considered. However, aciclovir is not registered for use during pregnancy, though the available data show no increase in the number of deformities in the children. A Caesarean section is recommended when there are active lesions at the time of childbirth. In cases where a first episode of herpes genitalis appears during the third trimester the birth must likewise be carried out by Caesarean section. Treatment with aciclovir, orally for the mother and intravenously for the child, should be started if the birth has to take place via the vaginal route.

Herpes zoster lesions occur in the region of a skin nerve (dermatoma). After healing a white band-shaped zone (depigmentation) or hyperpigmentation often remains. When the ophthalmic nerve is affected the eye can be damaged and blindness may occur. Many patients will develop herpes zoster, sometimes with several episodes and sometimes covering more than 1 dermatoma at the same time. If it is localised on the face, the eyes can be affected and blindness can occur. If the tip of the nose shows a lesion, the nasociliary branch of the ophthalmic nerve is involved. This makes corneal lesions very likely. Aciclovir (800 mg, 5 times per day), valaciclovir 1000 mg, 3 times per day or famciclovir (the prodrug of penciclovir) 500 mg, 3 times per day are used in the treatment. Post-herpetic neuralgia is difficult to treat. When customary analgesics or topical lidocaine have insufficient effect, the antidepressants nortriptyline, amitriptyline (Redomex®) or desipramine (Pertofran®) can be tried. Anticonvulsants such as carbamazepine or gabapentine can sometimes alleviate the pain. Opioids such as oxycodone can bring relief in some patients. A peripheral nerve blockade is an emergency solution. When analgesics bring no improvement, methylprednisolone may be administered intrathecally (the neuralgia has an inflammatory component).

Brivudin, an antiviral agent used in treating herpes zoster, is significantly more efficacious than standard aciclovir. Data also showed that brivudin is as effective as famciclovir in alleviating acute signs and symptoms of herpes zoster. Furthermore, brivudin, which is given orally at a dose of 125 mg once daily for seven days, improves patient compliance.

This virus of the herpes group can cause retinitis, pneumonitis, encephalitis and colitis. Ganciclovir (Cymevene®), foscarnet (Foscavir®), valganciclovir (Valcyte®) and cidofovir (Vistide®) are used in the treatment. These products are too expensive for use in developing countries. Ganciclovir is a nucleoside analogue [nucleoside = base + saccharide] and must be coupled intracellularly to 3 phosphate groups in order to be activated. The first phosphate is coupled by a viral kinase. The next two phosphate groups are attached by a cellular enzyme. The kinase of the virus can mutate and hence resistance can occur. Cidofovir is a nucleotide analogue [nucleotide = base + saccharide + phosphate] and must be coupled to 2 phosphate groups by cellular enzymes in order to be activated. Ganciclovir can be administered IV, PO or intraocularly. Its side-effects are haemato- and nephrotoxicity. When kidney function is reduced ganciclovir® is given in a dosage of 2 x 5 mg/kg/day (infusion over 1 hour). Maintenance therapy is 5 mg/kg/day for 7 days per week or 6 mg/kg/day for 5 days per week. In the West, maintenance therapy is often given via a Port-a-cath. Vitrasert is a minuscule shield impregnated with ganciclovir that can be surgically inserted into an eye, producing high concentrations in loco. Preventive oral ganciclovir therapy for CMV leads to resistance in 23% after one year. When kidney function is normal, treatment with foscarnet -a pyrophosphate analogue-, 180-200 mg/kg/day (normally 2 x 250 ml for an average adult, diluted for peripheral infusion) can be given as an alternative. The dose for maintenance therapy is 120 mg/kg/day. The principal side-effect of foscarnet is nephrotoxicity. Fomivirsen is an experimental anti-CMV product that is still being evaluated. Monthly maintenance eye injections of fomivirsen (Vitravene) are evaluated for resistant CMV retinitis. Lobucavir and adefovir (bis-POM-PMEA) are still in an experimental stage.

There is a close connection between HIV infection and tuberculosis. Many tuberculosis patients in Africa are HIV patients and approximately 50% of the HIV patients develop tuberculosis. This makes the struggle against tuberculosis much more difficult. The diminished resistance of the patient often results in a reactivation of tuberculosis bacteria. New infections of course also occur. Clinical symptoms of tuberculosis can appear quite early, even before the CD4-lymphocyte count has substantially decreased. Infections with atypical mycobacteria (for example MAI = Mycobacterium avium intracellulare) are more frequent in the West and seldom occur in developing countries. The discovery of acid-fast bacilli in a patient in Africa is therefore usually synonymous with tuberculosis. Most atypical mycobacterioses in fact occur only when the immunosuppression has advanced much further. However, many patients will have died before this stage is reached.

The Mantoux-test is unreliable in AIDS (frequently negative due to anergy). Tuberculosis proceeds more aggressively and quickly in HIV patients. Extrapulmonary tuberculosis occurs more in seropositive persons. Fortunately, treatment gives good results. Any new case of tuberculosis that has never been treated before should be given: isoniazid + rifampin + pyrazinamide + ethambutol for 2 months, followed by isoniazid + rifampin for 4 months. It is better not to give streptomycin injections due to the risk of HIV transmission in cases of poor sterilization of needles. AIDS patients often have severe cutaneous side-effects (including Stevens-Johnson syndrome) upon use of thiosemicarbazone, and hence this product is best avoided. The increase in resistant tuberculosis and the lack of cheap alternative therapies may in the near future give rise to extra problems, not only for the patients themselves but also for the non-seropositive population. Compliance with therapy is of utmost importance for the patients themselves and for preventing development of resistance and for counteracting further transmission (also to non-HIV infected persons). Respiratory precautions, till negativity of the sputum (Ziehl-Neelsen), should be implemented.

Active tuberculosis should be excluded before TB prophylaxis is started in a patient. INH (1 year) combined with pyridoxine (vitamin B6), the latter for prevention of neuritis, is used as prophylaxis. Rifampicin can be given with pyrazinamide for two months as an equally effective alternative.

Mycobacterium avium is not very sensitive to the conventional tuberculostatic drugs. Treatment of Mycobacterium avium relies on administration of rifabutin [Mycobutin®] + ethambutol [Myambutol®]+ clarithromycin [Maclar®, Biclar®, Heliclar®].

Certain cancers, including Kaposi's sarcoma and certain non-Hodgkin’s lymphomas, occur more frequently due to the immunosuppression. Seropositive women run an increased (5-fold) risk of invasive cervix carcinoma and of vulva carcinoma. This is probably connected with the sexually transmitted papilloma virus. Chemotherapy (vincristine + bleomycin, taxol), alpha-interferon (Intron®, Roferon-A®) and radiotherapy can reduce Kaposi lesions, but do not prolong life. These treatments are very expensive and often not available in developing countries. Kaposi lesions do often improve with HAART.

Schemes with killed vaccines such as those proposed by the WHO may be used, even in seropositive children and in children whose HIV status is not known. The live oral polio vaccine (Sabin) is better replaced by the inactivated Salk vaccine in known HIV+ children. BCG is best avoided in known HIV+ children. For safety’s sake yellow fever vaccination should be avoided, although the risks are probably minimal. More recent data indicate that vaccination is safe when the CD4-count is higher than 200. When the CD4-cells are more than 400, the immunogenicity of the vaccine is reliable.

The following vaccines are advised : Pneumovax, Tetanus, Hepatitis A and B, Influenza.

• PCP: Cotrimoxazole 1 per day or dapsone 100 mg per day or pentamidine 300 mg/month inhalation

• TB: INH 300 mg/day x 12 months or INH 300 mg/day + Rifampicin 600 mg/day x 2 months

• Toxoplasmosis: Cotrimoxazole 800/160 once per day or Dapsone 50 mg/day + pyrimethamine 50 mg/week + leukovorin 25 mg/week

Pathogen	Primary	Secondary
Pneumocystis carinii	CD4<200> Cotrimoxazole (160 mg trimethoprim + 800 mg sulfamethoxazole qd, 3d/week). Dapsone 100 mg + pyrimethamine 50 mg 2d/week. Aerosolised pentamidine 300 mg/month. Fansidar (500/25 mg), 1-2 days/week.	Previous episode of PCP Cotrimoxazole dosage identical to the primary prophylaxis Aerosolised pentamidine, 300 mg/15d. Pentamidine IV or IM, 4 mg/kg/month. Dapsone, 100 mg/d or 200 mg/week. Fansidar (500/25 mg), 1-2/week.
Toxoplasma gondii	CD4<100> Cotrimoxazole (160/800 mg) qd, 3d/week. Dapsone, 100 mg + Pyrimethamine 50 mg, 2 d/week. Pyrimethamine, 50 mg 3 d/week (+ folinic acid).	Previous episode of toxoplasmosis Sulphadiazine 2 g + pyrimethamine 25 mg + folinic acid 10 mg qd, daily; or sulphadiazine 2 gr + pyrimethamine 50 mg + folinic acid 10 mg qd 3 days per week Clindamycin, 600 mg tid + pyrimethamine, 25 mg + folinic acid, 10 mg qd. Clarithromycin 500 mg/12 h + pyrimethamine, 25 mg + folinic acid, 10 mg/d
Leishmania donovani	No	Previous episode of leishmaniasis Glucantime 20 mg/Kg/15-30 days
Isospora belli	No	Previous episode of isosporiasis Cotrimoxazole (160 mg trimethoprim + 800 mg sulphamethoxazole), 3 days/week. Fansidar 1 tablet/week
Cryptococcus neoformans	CD4<50> Fluconazole 100-200 mg qd	Previous episode of cryptococcosis Fluconazole 200 mg qd. Amphotericin B 100 mg/week IV
Candida sp.	No	Severe recurrent candidiasis Topical nystatin or miconazole. Fluconazole 50-100 mg qd Ketoconazole 200-400 mg qd Amphotericin B 0.2-0.3 mg/kg/d IV (oesophageal or Candida resistant to imidazoles).
Cytomegalovirus	CD4<50> Ganciclovir 1 g tid oral	Previous episode of retinitis Ganciclovir 5 mg/kg/d IV 5 d/week or 10 mg/kg/d 3 d/week or ganciclovir orally 1 g tid. Foscarnet 120 mg/kg/d IV in 2-3 h, 5 d/week. Cidofovir 5 mg/kg IV + probenecid every 2 weeks.
Herpes simplex	No	Frequent recurrence Aciclovir 200 mg tid or 400 mg bid Famciclovir 500 mg bid Valaciclovir 500 mg bid
Herpes zoster	Recent contact with VVZ and no prior incidents. VZIG 5 vials (of 1.25 ml) IM 48-96 h after exposure.	Frequent recurrence Aciclovir 800 mg bid or tid, if recurrence is frequent. Famciclovir 500 mg bid
M. tuberculosis	PPD+ (current or previous) without prophylaxis or prior treatment. Recent contact with open TB. Isoniazid 300 mg qd or 900 mg 2d/week, for 9 months. Rifampin 600 mg + pyrazinamide 20 mg/kd/d, 2 months Rifampin 600 mg/d for 4 months if there is a high probability of exposure to isoniazid-resistant TB.	No
M. avium-complex	CD4<50 Azithromycin 1200 mg/week Clarithromycin 500 mg bid Rifabutin 300 mg qd	Lifelong treatment
Histoplasma capsulatum	CD4<100,> Itraconazole 200 mg qd	Previous episode of histoplasmosis Itraconazole 200 mg bid Amphotericin B 1 mg/kg/week IV
Coccidioides immitis	No	Previous episode of coccidioidomycosis Fluconazole 400 mg qd Amphotericin B 1 mg/kg/week IV Itraconazole 200 mg/12 h
Salmonella sp. (non-typhi)	No	Episode of bacteraemia Ciprofloxacin 500 mg bid during several months
Streptococcus pneumoniae	CD4>200 Antipneumococcal vaccination 0.5 ml IM every 5 years. If previous dosage was applied when CD4<200,>200, then revaccinate
Hepatitis B	Negative markers for hepatitis B Hepatitis B vaccination (3 doses)
Influenza	HIV+, Flu vaccination 0.5 ml/year IM

Recommendations for the simultaneous administration of antiretroviral drugs with rifampin or rifabutin
Drug	With rifabutin	With rifampin	Comments
Saquinavir Hard gelatin capsules Soft gelatin capsules	Possible, if ritonavir is included in the regimen. Probable (dose: rifabutin 600 mg qd or 2-3 times/week) or 150 mg qd or 2-3 times/week.	Possible, if ritonavir is included in the regimen. Possible, if ritonavir is included in the regimen.	Pharmacokinetic data and clinical experience are limited. (dose: saquinavir 400 mg bid + ritonavir 400 mg bid) Pharmacokinetic data and clinical experience are limited. The co-administration of saquinavir + rifampin is not recommended without ritonavir.
Ritonavir	Probable (rifabutin: 150 mg 2-3 times/week)	Probable	Pharmacokinetic data and clinical experience on the co-administration of ritonavir + rifampin are limited.
Indinavir	Yes	No	Clinical data are limited but favourable. (dose indinavir: 800 mg tid or 1000 mg tid + rifabutin 150 mg qd or 300 mg 2-3 times per week).
Nelfinavir	Yes	No	Clinical data are limited but favourable. (dose nelfinavir: 750 mg tid or 1250 mg bid or 1000 mg tid + rifabutin 150 mg qd or 300 mg 2-3 times per week).
Amprenavir	Yes	No	No clinical experience, but should be possible with the normal dose of rifabutin.
Nevirapine	Yes	No	No published clinical experience. The combination would be possible with the normal dose of rifabutin.
Delavirdine	No	No
Efavirenz	Probable The combination is possible. (rifabutin: 450 mg or 600 mg qd, or 600 mg 2-3 times/week).	Probable. The combination is possible with the normal dose of rifampin + efavirenz 600 mg or 800 mg qd.

A final solution is expected from an AIDS vaccine. A number of theoretical approaches are being tested. On the one hand attempts are being made to find a vaccine that prevents infection itself, while on the other hand a vaccine that is administered to persons who are already infected and that influences the course of the infection in the good sense would be very useful. As AIDS vaccines are at present still in an experimental stage, prevention and control of the infection should be concentrated on three levels: sexual transmission, prevention of transmission via contaminated blood or needles, and mother-to-child transmission.

Information for the general population and for particular risk groups, counselling of seropositive persons, condom distribution (prostitutes), promotion of use and availability of condoms, counselling prostitutes, detection and treatment of other sexually transmitted diseases (STDs). In a number of countries it is the custom that after the death of the husband, the wife marries a brother or another member of the deceased’s family. This of course promotes transmission. In many countries the condom is still a very sensitive topic (taboo in public debates or even in private conversations within couples or family). One of the first actions to be taken in the campaign against AIDS in Thailand was the demystifying of the condom by all kinds of educational and promotional campaigns. In contrast to what is sometimes said, the promotion of condom use in tropical countries is not a hopeless task. It is being investigated whether a virocidal cream applied to the vagina offers some protection (so that women no longer have to depend on the good-will of their male partners). Circumcision of the man brings about a 2.5-fold decrease in the risk of HIV transmission from woman to man. It must be emphasised that circumcision does not give absolute protection.

Screening of blood for transfusion, limitation of blood transfusions and injections, strict sterilization of needles, syringes, etc. The intravenous drug abuse problem does not have the same proportions in Africa as it does in developed countries, though it is quite substantial in Southeast Asia. Medical personnel should avoid accidental contact with blood by wearing gloves, by not recapping needles, by putting needles immediately after use into containers with large openings, and by wearing protective clothing, masks, gloves and glasses when assisting childbirth. Hands should be washed with soap and water after contact with body fluids. Correct techniques should (of course!) be used in surgical operations. For example, during a surgical operation the handing over of a sharp instrument such as a scalpel should take place not from hand to hand, but the instrument should first be laid down, after which the next person picks it up. Making sterile needles and syringes available to drug users, as well as methadone projects, have proved useful.

Not all children born to seropositive mothers will be infected. Why some children are infected and others are not is a topic of intensive research. Seropositive women are advised to avoid conception. However, there are many women or married couples who do want a child to symbolically overcome death via their progeny. Breast-feeding should be discouraged if there is an alternative, though the latter is often not the case. Perinatal administration of Retrovir® definitely lowers the risk of transmission. In an American-European study in which Retrovir® was given IV to the mother throughout the third trimester of pregnancy and during childbirth and to the child for 4 weeks a decrease in transmission from 22% to 8% was observed. Shorter schemes with Retrovir® are also effective. Retrovir® appears to be tolerated very well by babies, with only minimal side-effects. In Third World countries Retrovir® will often be beyond the scope of many patients. Perinatal transmission can be reduced by 50% by a single administration of 200 mg nevirapine (Viramune®) to the mother during childbirth and by one dose (2 mg/kg) to the baby within the first 3 days of life. This should be a cheap strategy in Third World countries for reducing intra-partum transmission and transfer via the early maternal milk. Elective Caesarean section carries a significantly lower risk of transmission (about 10%). The advantage of a Caesarean section diminishes when the amniochorionic membranes are broken and/or the mother is already in labour. Combining prophylactic Retrovir® with elective Caesarean section can reduce the risk of vertical transmission to about 2%. The possible place of HAART in this setting is still not clear. Episiotomy, internal monitoring (in any case a luxury), forceps and vacuum extraction are best avoided in vaginal childbirth. After birth, the child should be gently aspirated, the eyes and nose flushed and given a quick bath to remove all blood. Optimal nutrition with enough vitamin A before giving birth is advised (the possibly inhibitory effect of certain retinoids on HIV is being investigated).