Prophylactic Treatment of HIV by Using Cotrimoxazole

HEALTH:

Many opportunistic infections can be prevented by using cotrimoxazole prophylaxis, particularly in the case of:

• Bacterial infection, e.g., pneumonia,
• Skin infection
• Sepsis
• Pneumocystis Jiroveci Pneumonia (PJP)
• Malaria
• Toxoplasmosis

Indications for Prophylactic Treatment Using Cotrimoxazole

Prophylactic treatment using Cotrimoxazole should be provided if any of the following criteria apply:

• Adults, adolescents, and pregnant women with CD4 cell count ≤350 cells/mm3
• Initiate CPT in all children < 5 years of age regardless of CD4 and WHO clinical stage
• All HIV exposed uninfected infants (initiate in all starting 4-6 weeks after birth)
• All HIV-infected persons with active TB

Dosage:

For adults: One double-strength tablet (160/800 mg) or two single strength tablets once a day on a daily basis. For those weight is<60 kg.

Criteria for Stopping:

• The occurrence of severe side effects such as severe cutaneous reactions or fixed drug reactions.
• If ART is initiated and CD4 count is above 350 cells/ml in adults and adolescents and virological suppression (<50 copies/mL).
• If a child is 5 years old and above with CD4 cell count above 350 cells/ml and viral suppression (<50 copies/mL).
• If the use of antiretroviral agents causes renal and/or hepatic insufficiency or severe hematological toxicity.

Follow up and Monitoring:

• Regular follow up is recommended, initially every month for the first three months, then every three months if the medication is well tolerated.
• It is mandatory to monitor for side effects and adherence. Monitoring includes the assessment of skin reactions, measurements of hemoglobin, and white blood counts every six months and when clinically indicated.

Note:

• Caution should be exercised when initiating cotrimoxazole Presumptive treatment (CPT) during the first trimester of pregnancy in women who may not have access to good nutrition; and anemic patients because cotrimoxazole can cause a deficiency in folic acid.
• CPT will continue to be provided to virologically suppressed patients (<50 copies/mL) with low CD4 cell counts (immunological non-responders).

COTRIMOXAZOLE:

The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole.

Trimethoprim is a diaminopyrimidine which selectively inhibits bacterial dihydrofolate reductase (DHFRase).

Sulfamethoxazole is the Sulfonamides considered to be derivatives of p-aminobenzoic acid’(PABA) which are Intermediate acting (8-12 hours).

It has slower oral absorption and urinary excretion resulting in intermediate duration of action; half-life in adults average 10 hours. It is the preferred compound for combining with trimethoprim because the half-life of both is similar.

However, a high fraction is acetylated, which is relatively insoluble-crystalluria can occur.

Adverse effects: All adverse effects seen with sulfonamides can be produced by cotrimoxazole.

• Nausea, vomiting, stomatitis, headache and rashes are the usual manifestations.
• Folate deficiency (megaloblastic anemia) is infrequent, occurs only in patients with marginal folate levels.
• Blood dyscrasias occur rarely.

Cotrimoxazole should not be given during pregnancy. Trimethoprim being an antifolate, there is theoretical teratogenic risk. Neonatal haemolysis and methaemoglobinaemia can occur if it is given near term.

• Patients with renal disease may develop uremia. Dose should be reduced in moderately severe renal impairment.
• A high incidence (up to 50%) of fever, rash and bone borrow hypoplasia has been reported among AIDS patients with Pneumocystis jiroveci infection when treated with high dose cotrimoxazole.
• The elderly are also at a greater risk of bone marrow toxicity from cotrimoxazole.
• Diuretics given with cotrimoxazole have produced a higher incidence of thrombocytopenia.

Uses:

Through cotrimoxazole is still used, its popularity in the treatment of systemic infections has declined. Common indications are:

1. Urinary tract infections: Most acute uncomplicated infections respond rapidly. Single dose therapy with 4 tablets of cotrimoxazole has been successfully for acute cystitis. Course of 3-10 days have been advised for lower and upper urinary tract infections, according to associated features. Cotrimoxazole is especially valuable for chronic or recurrent cases or in prostatis, because trimethoprim is concentrated in prostate.
2. Respiratory tract infections: Both upper and lower respiratory tract infections, including chronic bronchitis and facia-maxillary infections, otitis media caused by gram positive cocci and influenzae respond well.
3. Bacterial diarrheas and dysentery: Cotrimoxazole may be used for severe and invasive infections by coli, Shigella, nontyphoid Salmonella, and Y. enterocolitica. Though response rate is lower than previously, and fluoroquinolones are more commonly used, it is still a valuable alternative for empirical therapy of infective diarrhea.
4. Pneumocystis jiroveci: Causes severe pneumonia in neutropenic and AIDS patients. Cotrimoxazole has prophylactic as well as therapeutic value, but high doses are needed.
5. Chancroid: Cotrimoxazole (800+160 mg) BD for 14 days is a third choice, but less expensive, alternative to ceftriaxone, azithromycin or ciprofloxacin.
6. Typhoid: Initially Cotrimoxazole was an effective alternative to chloramphenicol. However, it has become unreliable, and is seldom used now.
7. Cotrimoxazole is an alternative to penicillin for protecting agranulocytosis patients and for treating respiratory or other infections in them. Intensive parenteral cotrimoxazole therapy has been used successfully in septicemias, but other drugs are commonly employed now.