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Part A: Module A2 Session 10

Prophylaxis of Opportunistic Infections. Part A: Module A2 Session 10. Objectives. Describe the prophylactic use of TMP/SMX and INH Describe the WHO recommendations for TMP/SMX and INH Understand when to prescribe prophylactic treatment, to whom and which regimen to use.

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Part A: Module A2 Session 10

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  1. Prophylaxis of Opportunistic Infections Part A: Module A2 Session 10

  2. Objectives • Describe the prophylactic use of TMP/SMX and INH • Describe the WHO recommendations for TMP/SMX and INH • Understand when to prescribe prophylactic treatment, to whom and which regimen to use

  3. Objectives, continued • Describe other preventive measures: 23-valent pneumococcal vaccine, antifungals, and hepatitis vaccine • Understand the purpose of secondary prevention and describe the relevant regimens • Discuss local and national guidelines regarding prophylaxis

  4. Prophylaxis for Selected OIs: Indications and Treatment Guidelines • Overview • Prophylaxis/preventive measures • Secondary prevention • Necessary drugs and equipment

  5. Overview

  6. OI prevention in resource constrained countries occurs in a context that is very different than what exists in Europe, North America, etc. • Many HIV/AIDS patients in Africa do not survive long enough to develop OIs such as CMV or MAC • Resources are limited. For the majority of patients, no CD4 counts are available, which would otherwise enable care providers to monitor disease progression • HIV infection is often not diagnosed until the patient is at an advanced stage of disease

  7. Common OIs in Resource Constrained Countries • Tuberculosis: widespread • Pneumococcal disease: widespread • Non-typhoid salmonellosis: particularly East and West Africa, Thailand, and Cambodia • Cryptococcosis: particularly East and South Africa, Thailand and Cambodia • PCP: South Africa and Asia • Penicilliosis: Thailand • Bacterial infections

  8. Some of the prevention measures recommended in the U.S. are not too expensive and may provide opportunities to prevent OIs in developing countries • TMP/SMX for PCP, cerebral toxoplamosis and various bacterial infections • INH for tuberculosis Indications for prophylaxis in resource constrained countries include use of the WHO clinical stage, and, where possible, CD4 count and viral load.

  9. Avoid unpasteurized dairy products, raw or undercooked eggs, meat, poultry, or fish (sources of salmonella) • Avoid undercooked or raw meat (source of toxoplasmosis) • If no safe water supply is available, patients and family should be advised to boil drinking water to avoid diarrheal diseases such as cryptosporidiosis • Moldy sugar cane or bamboo has been suggested as possible sources of Penicillium marneffei infection (in Thailand) General Prevention Measures

  10. Drugs for OI Prophylaxis

  11. Cotrimoxazole (TMP/SMX) • An effective prophylaxis against: • Various bacterial infections: Streptococcus pneumoniae, Salmonella species and Nocardia • Pneumocystis carinii • Toxoplasmosis • Isospora belli • Cyclospora UNAIDS recommends that Cotrimoxazole be part of a minimum package of care for adults and children living with HIV/AIDS in Africa.

  12. UNAIDS/WHO Cotrimoxazole Recommendations Candidates for cotrimoxazole prophylaxis should be recruited from all levels of health care facilities, AIDS service organizations and nongovernmental organizations Initial prescription of prophylaxis should be prescribed by trained health care personnel Counseling should be provided

  13. UNAIDS/WHO Cotrimoxazole Recommendations Prophylaxis should be offered to: • HIV positive adults (over age 13): all persons with symptomatic HIV (Stage II, III or IV); asymptomatic persons with CD4 count of 500 or less or total lymphocyte equivalent; pregnant women after 1st trimester • HIV exposed infants from 6 weeks of age: any child born to HIV infected mother; any child identified as HIV infected during the 1st year of life; any child older than 15 months who have had a PCP event, have symptomatic HIV disease, an AIDS defining illness or CD4 % less than 15

  14. UNAIDS/WHO Cotrimoxazole Recommendations, continued Recommended drug dosages Adults: 1 DS tablet or 2 SS tablets daily (1DS=SMX 800 mg+TMP 160 mg; 1SS=SMX 400 mg+TMP 80 mg) Children: Cotrimoxazole syrup administered 1/day, daily Recommended dose is TMP 10 mg/kg, SMX 50 mg/kg If syrup is unavailable, may use crushed tablets. Health professional may switch from syrup to tablet to ensure ongoing access to medication.

  15. OI Prophylaxis Duration of Treatment Prophylaxis should be given life-long for adults and children (>15 months)

  16. OI prophylaxis, continued For infants < 15 months: Prophylaxis should continue until HIV infection has been reasonably ruled out and there is no further risk of exposure For children > 15 months: Prophylaxis should be administered if child has • had a PCP event • has symptomatic HIV disease • has an AIDS-defining illness, or • has a CD4 percentage less than 15

  17. OI prophylaxis, cont’d. Criteria for Stopping Treatment (adults and children) • In the occurrence of severe cutaneous reactions such as fixed drug reaction andStevens Johnson syndrome, renal and/or hepatic failure, and severe hematological toxicity • If antiretroviral agents become available and when CD4 is greater than 500, prophylaxis can be stopped Adverse Reactions • Adverse reactions are common • Every effort should be made to continue prophylaxis • Lower doses are less effective than the recommended daily DS tablet

  18. OI prophylaxis, continued Alternative Regimens Dapsone 50 mg 2 x daily or 100 mg /day In patients with CD4<100 and positive toxoplasma antibodies, pyrimethamine 50 mg weekly + folinic acid 25 mg weekly should be added to regimen Pentamidine aerosols 300mg/month are more difficult to implement, less effective (PCP), effect not entirely understood (toxoplasmosis) In cases of non-life threatening adverse reactions, treatment should be stopped for 2 weeks, then the patient should be re-challenged with TMP/SMX in a gradually increasing dose

  19. OI prophylaxis, continued Follow upProphylaxis should be used where regular follow-up of patients is possible In adults, follow up should be every month and then every 3 months Children should be evaluated on monthly basis In adults and children, monitoring for toxicity, clinical events, and compliance to treatment should be undertaken. Monitoring of adults should also include hemoglobin and white blood counts every 6 months, where possible and when clinically indicated

  20. OI prophylaxis, continued Monitoring Each country should develop an implementation and monitoring plan for Cotrimoxazole prophylaxis Concurrent monitoring for clinical effectiveness is important, especially in areas where widespread resistance is present; in addition to prophylaxis investigation into new interventions is necessary

  21. OI prophylaxis, continued Evaluation Program evaluation and clinical effectiveness indicators will be developed by a task force led by UNAIDS. Could include surveillance for: • Background rates of OI and antimicrobial resistance • Changes in antimicrobial resistance • Acute and cumulative toxicities

  22. OI prophylaxis, continued Research Comparative studies to identify affordable alternative therapies Further studies on dose and time of initiation Willingness/ability to pay at the household level Household income, savings, expenses impact

  23. OI prophylaxis, continued Cost TMP/SMX in the recommended dose of 1DS daily costs $US 60/year Distribution Cotrimoxazole can be: Given through community clinics and home-care projects Integrated into counseling activities, favoring the regular follow up of the PLH/A by a counselor at the same time as the cotrimoxazole prescription is renewed

  24. Isoniazid (INH) • HIV infection is the strongest known risk factor the progression of latent TB infection to active TB • In countries with high TB prevalence, between 2.4% and 7.5% of HIV-infected adults may develop active TB each year • The mechanisms include reactivation of latent infection and/or a re-infection with Mycobacterium tuberculosis, characterized by a rapid progression towards active disease and a rapid progression of primary infection

  25. Isoniazid (INH), continued • Before the AIDS epidemic, preventive therapy for tuberculosis was never recommended in developing countries except for breast-feeding infants of mothers with PTB, or children < 5 years old living with infectious persons • Preventive therapy as a public health strategy is now being reconsidered because of the high incidence of TB in HIV-positive patients in developing countries • In the pre-AIDS era, several placebo-controlled trials in the USA and Europe demonstrated the efficacy of INH prevention in PPD-positive persons, which is believed to be at least 60% • The cost of this drug is about $US 60 per year

  26. Isoniazid (INH), continued • WHO Recommendations: Preventive therapy (PT) against tuberculosis in people living with HIV • Several large randomized controlled trials have now demonstrated that PT is effective in preventing TB in individuals dually infected with HIV and M. tuberculosis • However, studies of feasibility of PT demonstrate that the process required to target appropriate individuals, to exclude active TB, to deliver PT, and to achieve compliance is complex and inefficient

  27. WHO Isoniazid Recommendations Prerequisites The following should be in place before a PT service is considered: • Adequate capacity for HIV counseling • Sufficiently trained health care staff • Linkage between HIV care and TB control services • TB treatment services that have a high probability of curing cases of TB identified through the PT service (defaulter and failure rate <10%)

  28. WHO Isoniazid Recommendations, continued Recommendations to Governments 1. Preventive therapy against tuberculosisshould be part of a package of care for people living with HIV/AIDS 2. Preventive therapy should only be used in settings where it is possible to exclude active TB cases and to ensure appropriate monitoring and follow-up

  29. WHO Isoniazid Recommendations, continued • Information about tuberculosis, including preventive therapy, should be made available to people with HIV • Preventive therapy should be provided from within settings that include established voluntary counseling and testing (VCT) services for HIV

  30. WHO Isoniazid Recommendations, continued 5. The priority for TB control programmes continues to be the detection and cure of infectious tuberculosis cases 6. National authorities must regulate the procurement and supply of tuberculosis drugs in order to prevent the development of drug resistance

  31. WHO Isoniazid Recommendations, continued Those who test positive for HIV should receive • Counseling on tuberculosis: People living with HIV are at risk ofdeveloping TB. They should be given health education and encouraged to seek early diagnosis and treatment of cough and other symptoms suggestive of TB. 2) Screening for active TB: PT is inadequate treatment for active TB and could lead to the development of drug resistance if taken in such cases. Active TB should therefore be excluded before PT is started. Do chest x-ray before considering PT.

  32. WHO Isoniazid Recommendations, continued Target those most PT is recommended for PPD-positive HIV- likely tobenefit infected individuals who do not have activeTB In some settings it may not be feasible to perform PPD testing. Under these circumstances the following individuals may still be considered for preventive therapy if they are infected with HIV: • Those living in population with high TB prevalence • Health care workers • Household contacts of TB patients • Prisoners • Miners • Other groups at high risk of TB

  33. WHO Isoniazid Recommendations, continued INH alone is the recommended drug regimen forpreventive therapy to those without active tuberculosis Trials using combination treatment report higher rates of adverse drug reaction Isoniazid may be given as a daily, self-administered therapy for 6 months at a dose of 5 mg/kg to a maximum of 300 mg. These individuals should be seen monthly and given 1-month supply of medication at each visit.

  34. WHO Isoniazid Recommendations, continued Compliance may be improved by giving anadditional 2-week emergency buffer supply to be used if the individual has to defer his or her monthly review. Rifampicin-containing regimens are not recommended in order to eliminate the risk of promoting rifampicin resistance through inadequate screening procedures or by misuse of the tablets.

  35. WHO Isoniazid Recommendations, continued ContraindicationsPreventive therapy is contraindicated into PTpatients with active tuberculosis and in patients with active (chronic or acute) hepatitis Active tuberculosis must be excluded before beginning preventive therapy Isoniazid should be given with caution to individuals who consume alcohol daily

  36. Conclusions • Programs with Cotrimoxazole prevention for PLHA must show proof of good patient compliance and have strategies in place to follow-up defaulters • INH prophylaxis is recommended for all known HIV-infected persons,without performing a PPD test: • Active TB has to be excluded before starting PT • That is, only asymptomatic PLHA who are in WHO clinical stage 1 and 2 and who have a negative chest X-ray will be considered for PT • Patients who have are in clinical stage 3 with no other symptoms might also be candidates for starting preventive therapy

  37. Conclusions, continued • Dose of INH: 5 mg/kg, with a maximum of 300 mg daily, for a duration of 6 months. (WHO guidelines) • All projects that face difficulties in the control of TB should not start INH preventive therapy on a routine basis • Projects that want to implement PT should have close working relationships between HIV and TB services. The programmes need qualified staff for counseling, a high cure rate for TB and a low defaulter rate (<10%)  • All projects, except pilot projects in HIV/AIDS care, should follow the national guidelines •  Prophylactic Treatment as Recommended in the U. S. in appendix C

  38. Other Preventive Measures 23-valent pneumococcal vaccine • HIV infected at increased risk of invasive pneumococcal disease caused by streptococcus pneumoniae Antifungals • In some regions with an unusual high incidence of cryptococcal meningitis or P. marneffei, primary prophylaxis with fluconazole or itraconazole might be considered Hepatitis B vaccination • HIV-infected patients have a higher risk of hepatitis B because of common risk factors. Patients who are HIV-positive are more likely to develop chronic hepatitis

  39. Secondary Prevention

  40. Tuberculosis Tuberculosis • Until now, secondary prevention for TB has not been advocated • Extended therapy (beyond 6-9 months) has been shown to reduce the incidence of relapse, but showed no benefit in terms of survival • Although no firm recommendation can be made, the results of a Haiti study favors use of secondary INH prophylaxis in patients who had symptomatic HIV disease before the initial diagnosis and treatment of TB

  41. PCP PCP • TMP/SMX: 1 DS daily is the recommended dose. Tolerance is improved with lower doses

  42. Fungal Infections Fungal Infections • P. marneffei: Itraconazole 200 mg daily • Cryptococcus neoformans: Fluconazole 200 mg daily (1st choice), amphotericin B, IV, 1/week, or fluconazole 200 mg 3 x weekly • Oral Thrush/ Fluconazole 100-200 mg Oesophageal candidiasis daily only if :recurrences are severe and frequent • Toxoplasmosis: TMP/SMX 1DS daily • Mucocutaneous Acyclovir 200mg 3 x daily or Herpes Simplex: acyclovir 400 mg 2 x daily

  43. Necessary Drugs and Equipment

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