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ManageMent of Hepatitis C and HiV CoinfeCtion • In some cases (if CD4 nadir has never been
250 HIV/AIDS TREATMENT AND CARE CLINICAL PROTOCOLS FOR THE WHO EUROPEAN REGION 4.3. Hepatotoxicity of ARV drugs HAART is associated with a higher risk of hepatotoxicity (defined as at least two fold ALT/AST increase above upper limit of normal (ULN)) in HCV/HIV-coinfected patients than in HIV-monoinfected patients (30, 60–64). However, the incidence and risk factors for liver enzyme elevations in large cohorts of HCV/HIV-coinfected patients are not well defined. In several studies, however, independent risk factors for hepatotoxicity have been identified (30, 60–64): • previous liver transaminase elevations to a grade ≥ III • higher baseline alanine amino-transferase values • viral coinfection • high plasma drug levels • degree of immune damage (64). Hepatotoxicity has been associated with all currently used ARV drugs, but existing studies fail to demonstrate a consistent association between particular drugs or drug classes and the development of subsequent hepatotoxicity. Comparison of HAART regimens (single-PI, multiple-PI and NNRTIbased) has given inconsistent results for liver-tolerability in cohorts in which HCV/HIV-coinfected patients are underrepresented. • Acute hepatotoxicity: in a single cohort study involving HCV positive and negative patients, the use of NVF within 12 weeks of initiating treatment and the use of full-dose ritonavir (RTV) (600 mg BID) have been implicated (62). But most liver enzyme elevation events are sub-clinical and usually reverse spontaneously. NVP is not contraindicated in all HCV/HIV-coinfected subjects, but should be closely monitored when used in asymptomatic patients. A majority of experts recommend avoiding its use in patients with evidence of liver dysfunction. • Chronic hepatotoxicity: the prolonged use of nucleoside analogue reverse transcriptase inhibitors (especially of those having a strong affinity for mitochondrial deoxyribonucleic acid (DNA) polymerase, such as ddI and d4T) exposes treated patients to a risk of chronic mitochondrial toxicity, whose target, among other organs, is the liver. This toxicity, possibly exacerbated in some patients by the specific chronic toxicity of PIs on the liver, may lead to hepatic steatosis and worsen pre-existing fibrosis. 4.4. ARV dose adjustment in patients with cirrhosis • Like a majority of drugs metabolized in the liver, antiretroviral agents such as PIs and NNRTIs are metabolized with difficulty in patients with cirrhosis (65, 66). • Although the relationship between high plasma concentrations and toxicity is not constant for all antiretroviral agents, it has been clearly demonstrated for certain PIs, such as NFV, LPV and amprenavir (APV), and NNRTIs such as EFV (67–70). • Of the NRTIs, only ZDV and ABC are metabolized by liver enzymes other than cytochrome P450 (CYP) (65, 66). Consequently, use of PIs, NNRTIs, ZDV or ABC in patients with liverdecompensated cirrhosis requires dosage adjustment in order to avoid a risk of drug accumulation. However, little specific guidance has been established to precisely adapt ARV dosages in patients with cirrhosis.
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HIV/AIDS TREATMENT AND CARE Clinica
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© World Health Organization 2007 A
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iv Acknowledgements The editors wou
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vi Marco Vitoria (WHO headquarters)
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viii CRP C-reactive protein CS caes
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x LFT liver function test LGE linea
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xii TDM therapeutic drug monitoring
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xiv Introduction HIV is a chronic i
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Annex 7. Glossary .................
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HIV/AIDS TREATMENT AND CARE CLINICA
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HIV/AIDS TREATMENT AND CARE CLINICA
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10 HIV/AIDS TREATMENT AND CARE CLIN
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1 HIV/AIDS TREATMENT AND CARE CLINI
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I. Principles management of opportu
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management of opportunistic infecti
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Table 8. pcp second-line treatment
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Table 12. oesophageal and dissemina
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5.9.1.2. Treatment Table 15. treatm
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palliative care for people living w
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III. Initial evaluation palliative
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IV. Treatment palliative care for p
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Fig. 2. who analgesic ladder for ma
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Type of pain or treatment Usual sta
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Table 5. prevalence of symptoms in
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Type Symptoms Possible causes Disea
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Type Symptoms Possible causes Disea
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Table 22. Management of mania and B
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Table 24. Management of cough or di
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V. Special advice for terminal care
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Table 27. common manifestations in
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References palliative care for peop
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VI. Suggested minimum data to be co
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136 HIV/AIDS TREATMENT AND CARE CLI
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Contents I. Policy and principles .
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I. Policy and principles HIV/AIDS T
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HIV/AIDS TREATMENT AND CARE FOR INJ
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° bacterial pneumonia ° endocardi
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Social factors are: • homelessnes
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Table 3. Interactions between ARV d
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Other medications Use Rifampicin (R
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Table 5. Interactions of illicit dr
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Page 209 and 210: ANNEX 1 ASI6 C © 2004 University o
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I. Prevention strategies Prevention
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Prevention of HePatitis a, B, C and
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Prevention of HePatitis a, B, C and
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5. Contraceptive methods for women
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I. Policy issues Prevention of Hiv
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III. Initial evaluation Prevention
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Prevention of Hiv transmission from
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6. Fungal infections...............
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• Disseminated non-tuberculous my
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Annex 3. Rabies vaccines ..........
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442 hIv/aIds tReatment and caRe clI
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Contents I. Policy issues .........
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I. Policy issues post-exposure prop
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post-exposure prophylaxis for hiv i
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° condom use ° presence of STIs (
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Table 3. thre- drug arv regimens Pr
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VI. Suggested minimum data to be co
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History of antiretroviral treatment
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Test results: HBV: HCV: HIV: Post-t
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Infection control standard precauti
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The World Health Organization (WHO)
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