Impact of highly active antiretroviral therapy on incidence and management of human immunodeficiency virus-related opportunistic infections

Chien-Ching Hung1,2,* and Shan-Chwen Chang1

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


    Abstract
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
We review the changes in incidences of HIV-related opportunistic infections and the safety of discontinuation of primary and secondary prophylaxis for HIV-related opportunistic infections in patients achieving immune restoration after the introduction of highly active antiretroviral therapy (HAART). HIV-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of HAART or non-adherent to HIV care and HAART, and those in whom non-HIV-related infections have emerged as a significant cause of morbidity and mortality in the post-HAART era. Clinical studies of patients with tuberculosis and HIV co-infection are reviewed to provide appropriate regimen combinations of rifamycins and antiretrovirals, which have varying degrees of drug–drug interactions that have posed challenges in the management of tuberculosis as well as HIV infection.

Keywords: HIV infection , AIDS , HAART , opportunistic infections , antimicrobial prophylaxis


    Introduction
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
With the introduction of antimicrobial prophylaxis and highly active antiretroviral therapy (HAART), the morbidity and mortality of HIV-infected patients receiving HAART have declined,1,2 and the decline has been sustained.2 The incidences of nearly all AIDS-defining opportunistic infections (OIs) have decreased significantly.3 HAART has changed HIV infection from a debilitating fatal disease to a chronic manageable disease. Discontinuation of primary and secondary prophylaxis against several major AIDS-defining OIs has been recommended in patients with immune restoration after HAART.4 However, HIV-related OIs and deaths continue to occur in patients newly diagnosed with HIV infection, in those in the early course of HAART, or in those non-adherent to HIV care and HAART,3,59 and non-HIV-related infections, such as sepsis and chronic viral hepatitis, have emerged as significant causes of death in the post-HAART era.8,10, In addition, the complexity of drug–drug interactions between rifamycins and antiretrovirals has posed challenges in the management of tuberculosis (TB) and HIV co-infection. Our objective was to review the impact of HAART on the incidence and management of HIV-related OIs and to provide appropriate antituberculous therapy containing rifamycins and antiretroviral therapy combinations in patients with TB and HIV co-infection.


    Bacterial infection
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
The proportion of recurrent bacterial pneumonia as an AIDS-defining OI of the respiratory tract appears to be stable or slightly in decline in the post-HAART era;9 Streptococcus pneumoniae remains the most common aetiological agent of community-acquired bacterial pneumonia, although in a large number of cases the aetiologies are unidentified despite the use of extensive testing.7 With wider use of HAART and antimicrobial prophylaxis, the incidence of invasive pneumococcal disease among HIV-infected persons has declined in the post-HAART era.12 In a laboratory-based surveillance study conducted in San Francisco,12 the quarterly incidence of invasive pneumococcal disease decreased from 10.6 cases per 1000 person-years (PY) in 1994 to 4.2 cases per 1000 PY in patients with AIDS in 1997 (P=0.004), with the most significant decrease occurring during 1996–1997.

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 1994–1995 to 3.8 episodes per 100 PY in 1997–1998;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


    Fungal infection
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
The incidence of Pneumocystis jiroveci pneumonia [formerly known as P. carinii pneumonia (PCP)] has declined,1,3 and survival following severe PCP has improved in patients receiving HAART.18 In the patients receiving primary or secondary prophylaxis against pneumocystosis and responding to HAART with resultant increases of CD4 lymphocyte counts to >200 cells/mm3 for more than 3 months, the risk for pneumocystosis is sufficiently low to warrant discontinuation of prophylaxis.1921 However, pneumocystosis continues to be a leading cause of community-acquired pneumonia, resulting in mortality among AIDS patients in the post-HAART era3,510 because of patient non-adherence to antimicrobial prophylaxis and failure to use antiretroviral therapy.3,6

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 case–control 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


    Mycobacteriosis
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
TB and HIV infection may be mutually detrimental in patients with co-infection; TB may accelerate the progression of HIV infection and be associated with a higher mortality rate and a shorter survival, whereas HIV infection increases the risk for development of active TB and TB recurrence in patients without HAART. In patients with access to HAART and rifampicin-containing antituberculous therapy, the incidence, recurrence and mortality rate of TB appear to be declining and survival improving.3032 The use of HAART has been found to be associated with a >80% reduction in the risk of TB.30,31

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 drug–drug 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


View this table:
[in this window]
[in a new window]
 
Table 1. Combinations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors with rifampicin or rifabutin based on clinical studies in HIV-infected patients with active tuberculosis

 
Disseminated infection due to non-tuberculous mycobacteria occurs mostly in patients with CD4 lymphocyte counts <50 cells/mm3, with Mycobacterium avium complex (MAC) the most common aetiology. With the introduction of HAART, the incidence of disseminated MAC infection has declined,1,3 and the prognosis of patients with disseminated MAC infection has been significantly improved.42 In the Adult and Adolescent Spectrum of Disease (ASD) Project, the incidence of disseminated MAC infection decreased from 10 cases per 100 PY in 1992 to two cases per 100 PY in 1998.3 Studies have shown that primary prophylaxis can be safely discontinued in patients with an increase of CD4+ count to >100 cells/mm3.43,44 Although the study design might be different and criteria for discontinuation of secondary prophylaxis varied, the rate of relapse of disseminated MAC infection was low in patients responding to HAART, with an increase in the CD4+ count to >100 cells/mm3.28,4547 Therefore, it has been recommended that secondary prophylaxis can also be discontinued in asymptomatic patients who complete a 12 month course of anti-MAC therapy and whose CD4+ cell count has been increased to >100 cells/mm3 for at least 6 months.4


    Viral infection
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
Reactivation of latent cytomegalovirus (CMV) infection in patients with CD4 lymphocyte counts of <50 cells/mm3 is associated with decreased survival, and the incidence and mortality rate of CMV disease have declined with HAART and anti-CMV therapy.1,3,48 Although there is no randomized study to assess the safety level of the CD4 count on discontinuation of maintenance anti-CMV therapy, clinical studies suggest that it is safe to discontinue secondary prophylaxis against CMV retinitis in patients with quiescent CMV retinitis who have sustained an increase in CD4 counts in response to HAART.49,50

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 4–6 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


    Parasitic infections
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
Toxoplasma encephalitis (TE) is a life-threatening opportunistic infection of the central nervous system in patients at advanced stage of HIV infection. The incidence of TE in HIV-infected patients may depend on geography and ethnicity, the degree of immunosuppression and use of antimicrobial prophylaxis, such as trimethoprim/sulfamethoxazole and HAART. It is estimated that 20%–47% of the patients seropositive for Toxoplasma gondii in the pre-HAART era will ultimately develop TE. The risk for TE has declined in HIV-infected patients who receive trimethoprim/sulfamethoxazole prophylaxis and HAART with immune restoration.3,58 In a French hospital-based surveillance study, the incidence of TE decreased from 3.9 per 100 PY in the pre-HAART era to 1.0 per 100 PY; among patients whose CD4 cell counts increased to >200 cells/mm3 after HAART, the incidence decreased further to 0.1 per 100 PY.58 Although no randomized clinical trials have compared the safety of discontinuation of primary or secondary prophylaxis, many studies have demonstrated that the occurrence of TE was rare after discontinuation of primary and secondary prophylaxis against pneumocystosis and TE in patients with restoration of immunity.1921,28,46

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


    Conclusions
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
To conclude, sufficient clinical data have demonstrated a decline in the incidence of nearly all HIV-related OIs, and discontinuation of primary or secondary prophylaxis for pneumocystosis, cryptococcal meningitis, histoplasmosis, disseminated MAC infection, CMV retinitis and TE is safe among HIV-infected patients responding to HAART. However, OIs continue to occur in patients who seek HIV care late, have limited access to HIV care or have poor compliance with antimicrobial prophylaxis and HAART. Therefore, more effort is needed to provide easy access to HIV care services, expand the availability of HAART and constantly reinforce patient adherence to antiretroviral and antimicrobial therapies.


    Acknowledgements
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
We thank Dr Victor L. Yu, Section of Infectious Diseases, Veterans Affair Medical Center, Pittsburgh, for reviewing this manuscript.


    Footnotes
 
* Correspondence address. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. Tel: +886-2-23123456 ext. 8265; Fax: +886-2-23223905; Email: hcc0401{at}ha.mc.ntu.edu.tw


    References
 Top
 Abstract
 Introduction
 Bacterial infection
 Fungal infection
 Mycobacteriosis
 Viral infection
 Parasitic infections
 Conclusions
 Acknowledgements
 References
 
1 . Palella, F. J. Jr., Delaney, K. M., Moorman, A. C. et al. (1998). Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine 338, 853–60.[Abstract/Free Full Text]

2 . Mocroft, A., Ledergerber, B., Katlama, C. et al. (2003). Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 362, 22–9.[ISI][Medline]

3 . Kaplan, J. E., Hanson, D., Dworkin, M. S. et al. (2000). Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United Stated in the era of highly active antiretroviral therapy. Clinical Infectious Diseases 30, S5–14.[CrossRef][ISI][Medline]

4 . USPHS/IDSA Prevention of Opportunistic Infections Working Group. (2002). 2002 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Morbidity and Mortality Weekly Report 51, (RR-08), 1–64.[Medline]

5 . Michelet, C., Arvieux, C., François, C. et al. (1998). Opportunistic infections occurring during highly active antiretroviral treatment. AIDS 12, 1815–22.[CrossRef][ISI][Medline]

6 . Lundberg, B. E., Davidson, A. J., Burman, W. J. et al. (2000). Epidemiology of Pneumocystis carinii pneumonia in an effective prophylaxis: the relative contribution of non-adherence and drug failure. AIDS 14, 2559–66.[CrossRef][ISI][Medline]

7 . Rimland, D., Navin, T. R., Lennox, J. L. et al. (2002). Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. AIDS 16, 85–95.[CrossRef][ISI][Medline]

8 . Jain, M. K., Skiest, D. J., Cloud, J. W. et al. (2003). Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatients deaths in 1995 and in 1999–2000. Clinical Infectious Diseases 36, 1030–8.[CrossRef][ISI][Medline]

9 . Serraino, D., Puro, V., Boumis, E. et al. (2003). Epidemiological aspects of major opportunistic infections of the respiratory tract in persons with AIDS: Europe, 1993–2000. AIDS 17, 2109–16.[CrossRef][ISI][Medline]

10 . Louie, J. K., Hsu, L. C., Osmond, D. H. et al. (2003). Trends in causes of death among persons with acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy San Francisco, 1994–1998. Journal of Infectious Diseases 186, 1023–7.[CrossRef][ISI]

11 . Bica, I., McGovern, B., Dhar, R. et al. (2001). Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clinical Infectious Diseases 32, 492–7.[CrossRef][ISI][Medline]

12 . Nuroti, J. P., Butler, J. C., Gelling, L. et al. (2000). Epidemiologic relationship between HIV and invasive pneumococcal disease in San Francisco County California. Annals of Internal Medicine 132, 182–90.[Free Full Text]

13 . French, N., Nakiyingi, J., Carpenter, L. M. et al. (2000). 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomized and placebo controlled trial. Lancet 355, 2106–11.[CrossRef][ISI][Medline]

14 . Klugman, K. P., Madhi, S. A., Huebner, R. E. et al. (2003). A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV Infection. New England Journal of Medicine 349, 1341–8.[Abstract/Free Full Text]

15 . Dworkin, M. S., Ward, J. W., Hanson, D. L. et al. (2001). Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clinical Infectious Diseases 32, 794–800.[CrossRef][ISI][Medline]

16 . Tumbarello, M., Tacconella, E., de Gaetano Donati, K. et al. (2000). HIV-associated bacteraemia: how it has changed in the highly active antiretroviral therapy (HAART) era. Journal of Acquired Immune Deficiency Syndromes 23, 145–51.[ISI][Medline]

17 . Hung, C. C., Hsieh, S. M., Hsiao, C. F. et al. (2001). Risk of recurrent nontyphoid Salmonella bacteraemia after early discontinuation of ciprofloxacin as secondary prophylaxis in HIV-1-infected patients in the era of highly active antiretroviral therapy. AIDS 15, 645–7.[CrossRef][ISI][Medline]

18 . Morris, A., Wachter, R. M., Luce, J. et al. (2003). Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia. AIDS 17, 73–80.[CrossRef][ISI][Medline]

19 . Furrer, H., Egger, M., Opravil, M. et al. (1999). Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. New England Journal of Medicine 340, 1301–6.[Abstract/Free Full Text]

20 . Lopez Bernado de Quiro, J. C., Miro, J. M., Pena, J. M. et al. (2001). A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. New England Journal of Medicine 344, 159–67.[Abstract/Free Full Text]

21 . Ledergerber, B., Mocroft, A., Reiss, P. et al. (2001). Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. New England Journal of Medicine 344, 168–74.[Abstract/Free Full Text]

22 . Mirza, S. A., Phelan, M., Rimland, D. et al. (2003). The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clinical Infectious Diseases 36, 789–94.[CrossRef][ISI][Medline]

23 . Dromer, F., Mathoulin-Pelissier, S., Fontanet, A. et al. (2004). Epidemiology of HIV-associated cryptococcosis in France (1985–2001): comparison of the pre-and post-HAART eras. AIDS 18, 555–62.[ISI][Medline]

24 . Hajjeh, R. A., Pappas, P. G., Henderson, H. et al. (2001). Multicentre case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons. Clinical Infectious Diseases 32, 1215–20.[CrossRef][ISI][Medline]

25 . Woods, C. W., McRill, C., Plikaytis, B. D. et al. (2000). Coccidioidomycosis in human immunodeficiency virus-infected persons in Arizona, 1994–1997: incidence, risk factors, and prevention. Journal of Infectious Diseases 181, 1428–34.[CrossRef][ISI][Medline]

26 . Supparatpinyo, K., Perriens, J., Nelson, K. E. et al. (1998). A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus. New England Journal of Medicine 339, 1739–43.[Abstract/Free Full Text]

27 . Mussini, C., Pezzotti, P., Miro, J. M. et al. (2004). Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy: an international observational study. Clinical Infectious Diseases 38, 565–71.[CrossRef][ISI][Medline]

28 . Kirk, O., Reiss, P., Uberti-Foppa, C. et al. (2002). Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy. Annals of Internal Medicine 137, 239–50.[Abstract/Free Full Text]

29 . Goldman, M., Zackin, R., Fichtenbaum, C. J. et al. (2004). Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clinical Infectious Diseases 38, 1485–9.[CrossRef][Medline]

30 . Girardi, E., Antonucci, G., Vanacore, P. et al. (2000). Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection. AIDS 14, 1985–91.[CrossRef][ISI][Medline]

31 . Santoro-Lopes, G., de Pinho, A. M., Harrison, L. H. et al. (2002). Reduced risk for tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clinical Infectious Diseases 34, 543–6.[CrossRef][ISI][Medline]

32 . Hung, C. C., Chen, M. Y., Hsiao, C. F. et al. (2003). Improved outcomes of HIV-1-infected adults with tuberculosis in the era of highly active antiretroviral therapy. AIDS 17, 2615–22.[CrossRef][ISI][Medline]

33 . Dean, G. L., Edwards, S. G., Ives, N. J. et al. (2002). Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS 16, 75–83.[CrossRef][ISI][Medline]

34 . Narita, M., Stambough, J. J., Hollender, E. S. et al. (2000). Use of rifabutin with protease inhibitors for human immunodeficiency virus-infected patients with tuberculosis. Clinical Infectious Diseases 30, 779–83.[CrossRef][ISI][Medline]

35 . Weiner, M., Peloquin, C., Khan, A. et al. (2004). Intermittent rifabutin and isoniazid with daily efavirenz in combination with 2 nucleosides for treatment of HIV infection and tuberculosis diseases. In Program and Abstracts of the Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, 2004. Abstract 761. Foundation for Retrovirology and Human Health, Alexandra, VA, USA.

36 . Lopez-Cortes, L., Ruiz-Valderas, R., Viciana, P. et al. (2002). Pharmacokinetic interactions between efavirenz and rifampin in HIV-infected patients with tuberculosis. Clinical Pharmacokinetics 41, 681–90.[ISI][Medline]

37 . Patel, A., Patel, K., Patel, J. et al. (2003). To study the safety and antiretroviral efficacy of rifampicin and efavirenz in antiretroviral-naive tuberculosis co-infected HIV-1 patients in India. In Program and Abstracts of the Tenth Conference on Retroviruses and Opportunistic Infections, Boston, MA, 2003. Abstract 138. Foundation for Retrovirology and Human Health, Alexandra, VA, USA.

38 . Pedral-Samapio, D., Alves, C., Netto, E. et al. (2003). Efficacy of efavirenz 600 mg dose in the ARV therapy regimen for HIV patients receiving rifampicin in the treatment of tuberculosis. In Program and Abstracts of the Tenth Conference on Retroviruses and Opportunistic Infections, Boston, MA, 2003. Abstract 784. Foundation for Retrovirology and Human Health, Alexandra, VA, USA.

39 . Hung, C. C., Lee, H. C., Hsieh, S. M. et al. (2004). Effectiveness of highly active antiretroviral therapy and antituberculous therapy combinations among HIV-infected patients with active tuberculosis. In Program and Abstracts of the Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, 2004. Abstract 763. Foundation for Retrovirology and Human Health, Alexandra, VA, USA.

40 . Lourtau, L., Toibaro, J., Garcia, O. et al. (2004). Retrospective comparison of 3 antiretroviral treatment of options in patients with HIV infection receiving rifampin. In Program and Abstracts of the Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, 2004. Abstract 762. Foundation for Retrovirology and Human Health, Alexandra, VA, USA.

41 . Friedland, G., Abdool Karim, S., Abdool Karim, Q. et al. (2004). Utility of tuberculosis directly observed therapy programs as sites for access to and provision of antiretroviral therapy in resource-limited countries. Clinical Infectious Diseases 38, S421–8.[CrossRef][ISI][Medline]

42 . Horsburgh, C. R. Jr., Gettings, J., Alexander, L. N. et al. (2001). Disseminated Mycobacterium avium complex disease among patients infected with human immunodeficiency virus, 1985-2000. Clinical Infectious Diseases 33, 1938–43.[CrossRef][ISI][Medline]

43 . El-Sadr, W. M., Burman, W. J., Grant, L. B. et al. (2000). Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. New England Journal of Medicine 342, 1085–92.[Abstract/Free Full Text]

44 . Currier, J. S., William, P. L., Koletar, S. L. et al. (2000). Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, doubled-blinded, placebo-controlled trial. Annals of Internal Medicine 133, 493–503.[Abstract/Free Full Text]

45 . Shafran, S. D., Mashinter, L. D., Phillips, P. et al. (2002). Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy. Annals of Internal Medicine 137, 734–7.[Abstract/Free Full Text]

46 . Zeller, V., Truffot, C., Agher, R. et al. (2002). Discontinuation of secondary prophylaxis against disseminated Mycobacterium avium complex infection and toxoplasmic encephalitis. Clinical Infectious Diseases 34, 662–7.[CrossRef][ISI][Medline]

47 . Aberg, J. A., Williams, P. L., Liu, T. et al. (2003). A study of discontinuing maintenance therapy in human immunodeficiency virus-infected subjects with disseminated Mycobacterium avium complex: AIDS Clinical Trial Group 393 Study Team. Journal of Infectious Diseases 187, 1046–52.[CrossRef][ISI][Medline]

48 . Kempen, J. H., Jabs, D. A., Wilson, L. A. et al. (2003). Mortality risk for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clinical Infectious Diseases 37, 1365–73.[CrossRef][ISI][Medline]

49 . Whitcup, S. M., Fortin, E., Lindblad, A. S. et al. (1999). Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis. JAMA 282, 1633–7.[Abstract/Free Full Text]

50 . Jouan, M., Savès, M., Tubiana, R. et al. (2001). Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy. AIDS 15, 23–31.[CrossRef][ISI][Medline]

51 . Tassie, J., Gasnault, J., Bentata, M. et al. (1999). Survival improvement of AIDS-related progressive multifocal leukoencephalopathy. AIDS 13, 1881–7.[CrossRef][ISI][Medline]

52 . Berenguer, J., Miralles, P., Arrizabalaga, J. et al. (2003). Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy. Clinical Infectious Diseases 36, 1047–52.[CrossRef][ISI][Medline]

53 . Greub, G., Ledergerber, B., Battegay, M. et al. (2000). Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection. Lancet 356, 1800–5.[CrossRef][ISI][Medline]

54 . Sulkowski, M. S., Moore, R. D., Mehta, S. H. et al. (2002). Hepatitis C and progression of HIV disease. JAMA 288, 199–206.[Abstract/Free Full Text]

55 . Sulkowski, M. S., Thomas, D. L., Chaisson, R. E. et al. (2000). Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 283, 74–80.[Abstract/Free Full Text]

56 . Sheng, W. H., Chen, M. Y., Hsiao, C. F. et al. (2004). Impact of chronic hepatitis B infection on outcomes of HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in an area hyperendemic for hepatitis B Infection. Clinical Infectious Disease 38, 1476–82.[ISI]

57 . Sulkowski, M. S., Mast, E. E., Seeff, L. B. et al. (2000). Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clinical Infectious Disease 30, S77–84.[CrossRef][ISI][Medline]

58 . Abgrall, S., Rabaud, C., Costagliola, D. et al. (2001). Incidence and risk factors for toxoplasmic encephalitis in human immunodeficiency virus-infected patients before and during the highly active antiretroviral therapy era. Clinical Infectious Diseases 33, 1747–55.[CrossRef][ISI][Medline]

59 . Foudraine, N. A., Weverling, G. J., van Gool, T. et al. (1998). Improvement of chronic diarrhoea in patients with advanced HIV-1 infection during potent antiretroviral therapy. AIDS 12, 35–41.[CrossRef][ISI][Medline]

60 . Carr, A., Marriot, D., Field, A. et al. (1998). Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 351, 256–61.[CrossRef][ISI][Medline]





This Article
Abstract
FREE Full Text (PDF)
All Versions of this Article:
54/5/849    most recent
dkh438v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Hung, C.-C.
Articles by Chang, S.-C.
PubMed
PubMed Citation
Articles by Hung, C.-C.
Articles by Chang, S.-C.