1 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine; 2 Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
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Abstract |
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Keywords: HIV infection , AIDS , HAART , opportunistic infections , antimicrobial prophylaxis
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Introduction |
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Bacterial infection |
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Whether pneumococcal vaccination can reduce the risk of invasive pneumococcal disease in HIV-infected patients remains controversial. In patients without HAART, vaccination with a 23-valent polysaccharide pneumococcal vaccine in HIV-infected Ugandan adults showed an increase in the rate of pneumococcal disease in vaccine recipients,13 whereas vaccination with a 9-valent conjugate vaccine in HIV-infected and HIV-uninfected children in South Africa showed reduced rates.14 Although an observational study suggested that receipt of antiretroviral therapy, especially HAART, and pneumococcal vaccination were associated with a decreased risk for pneumococcal disease,15 more studies are needed to assess whether receipt of HAART will enhance the serological response to pneumococcal vaccination and clinical benefit.
The incidence of HIV-associated community-acquired bacteraemia has declined in the post-HAART era.16 In an Italian university hospital for HIV care, the incidence of HIV-associated community-acquired bacteraemia declined from six episodes per 100 PY in 19941995 to 3.8 episodes per 100 PY in 19971998;16 the most evident reduction occurred for non-typhoid Salmonella, whereas the rate of S. pneumoniae bacteraemia remained constant over the two study periods.16
Non-typhoid Salmonella bacteraemia is associated with a high recurrence rate in HIV-infected patients despite suppressive therapy with ciprofloxacin in the pre-HAART era. Although the optimal duration of suppressive therapy to prevent recurrences of non-typhoid Salmonella bacteraemia remains unclear in patients responding to HAART, it appears to be safe to discontinue ciprofloxacin 1 month after concurrent HAART.17
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Fungal infection |
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Surveillance studies in the USA and France have documented the significantly decreasing incidence of cryptococcosis in the post-HAART era.22,23 In the Atlanta area, the incidence of cryptococcosis among patients with AIDS decreased from 66 cases per 1000 PY in 1992 to seven cases per 1000 PY in 2000, whereas in the Houston area, the incidence decreased from 23.6 cases per 1000 person-years to 1.6 cases per 1000 PY.22 In France, the incidence of HIV-associated cryptococcosis has decreased by 46% during the post-HAART era.23 However, HIV-infected patients with limited access to HIV care continue to develop cryptococcosis in the post-HAART era with the same incident mortality as seen earlier.22,23
Infections due to endemic fungi, such as Histoplasma capsulatum,24 Coccidioides immitis25 and Penicillium marneffei,26 usually develop in patients at an advanced stage of HIV infection, and relapse rates are high in those patients not receiving maintenance antifungal prophylaxis. In casecontrol studies, use of antiretroviral therapy and antifungal prophylaxis has been found to be associated with a reduced risk, although the mortality did not improve in the patients who developed infections due to endemic fungi.24,25
Studies supporting the discontinuation of maintenance antifungal therapy are emerging in selected cases of cryptococcosis27,28 and histoplasmosis.29 A multicentre study of discontinuation of suppressive antifungal therapy with fluconazole or itraconazole to prevent relapse of cryptococcal meningitis in patients receiving HAART demonstrated that discontinuation of antifungal therapy when the CD4 count increased to 100 cells/mm3 was associated with a low risk of relapse, even in patients with detectable plasma viral load or cryptococcal antigenaemia.27 Similarly, discontinuation of maintenance antifungal therapy was safe in patients with histoplasmosis who received at least 12 months of antifungal therapy and 6 months of antiretroviral therapy and had negative blood cultures, urine and serum Histoplasma antigen <4.1 units and CD4 count >150 cells/mm3.29
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Mycobacteriosis |
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In patients with TB and HIV co-infection, the optimal management of these two diseases concurrently has been a challenge to HIV care providers, and the appropriate timing of initiation of HAART is not clear because of a high pill burden, toxicity and drugdrug interactions between rifamycins, protease inhibitors and non-nucleoside reverse transcriptase inhibitors. A high proportion of patients have had to change their antiretroviral therapy or antituberculous therapy because of toxicity.33 For patients with CD4 counts <100 cells/mm3, antiretroviral therapy should be started early because delayed HAART in such TB patients may increase the risk for death or HIV progression;33 for patients with higher CD4 counts, HAART may be delayed until the continuation phase (after 2 months of antituberculous therapy), or until the end of antituberculous therapy.33
Rifampicin may interact pharmacokinetically with protease inhibitors, accelerating their metabolism through the induction of P450 cytochrome oxidase (CYP 450), which may result in sub-therapeutic serum levels of protease inhibitors. In addition, protease inhibitors retard the metabolism of rifabutin, resulting in increased serum levels of rifabutin and an increased likelihood of drug toxicities. Rifabutin, with its lower induction capability of the CYP 450 enzyme, is recommended when combined with efavirenz or protease inhibitors (Table 1).34,35 Recently, clinical studies have demonstrated that combinations of efavirenz or nevirapine plus two nucleoside reverse transcriptase inhibitors with rifampicin (10 mg/kg)-containing antituberculous therapy are good alternatives to HAART and antituberculous therapy combinations because of a lower pill burden and good clinical efficacy (Table 1).3640 In addition, once-daily HAART containing efavirenz makes integration of directly observed therapy for TB and HIV infection possible.41
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Viral infection |
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Progressive multifocal leucoencephalopathy (PML), a demyelinating disease of the central nervous system caused by the human polyomavirus JC virus, leading almost invariably to death a median of 46 months after diagnosis, has been increasingly diagnosed as a result of HIV-induced immunosuppression. Although the effect of HAART on the incidence of AIDS-associated PML remains to be studied, the use of HAART has been shown to prolong survival, improve neurological function and reduce the size of active PML lesions on radiographic images.51,52
Seroprevalence of co-infection with hepatitis B or C virus varies with populations studied.5356 Although chronic hepatitis B or C infection is not a classical AIDS-defining OI, it has been considered an OI in HIV-infected patients because such co-infection may be associated with higher risk for disease progression and shorter survival.57 Risk for hepatotoxicity is also significantly higher in patients with co-infection, which may affect the virological response to HAART.55,56 When survival of HIV-infected patients is prolonged in the post-HAART era, hepatic complications due to chronic hepatitis B or C infection have emerged as an increasingly important cause of morbidity and mortality.8,10,11
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Parasitic infections |
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Cryptosporidium parvum and microsporidia are the two common opportunistic parasites that cause chronic diarrhoea and wasting in HIV-infected patients with CD4 counts <100 cells/mm3, and antimicrobial agents have limited efficacy in preventing or eradicating infections with cryptosporidia or microsporidia among HIV-infected patients. Although studies assessing the changes of incidence of cryptosporidiosis and microsporidiosis are lacking, diarrhoea due to microsporidia and cryptosporidia resolved spontaneously with immune restoration among HIV-infected patients who responded to HAART.59,60
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Conclusions |
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Acknowledgements |
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Footnotes |
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References |
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