Original Article
Discontinuation of Secondary Prophylaxis against Pneumocystis carinii Pneumonia in Patients with HIV Infection Who Have a Response to Antiretroviral Therapy
N Engl J Med 2001; 344:168-174January 18, 2001
- Abstract
Background
Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known.
Methods
We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter.
Results
Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter).
Conclusions
It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy.
Media in This Article
Figure 1
Evolution of CD4 Cell Counts in 325 Patients with HIV Infection and a History of P. carinii Pneumonia in Whom Highly Active Antiretroviral Therapy Was Initiated and Secondary Prophylaxis Was Subsequently Discontinued after CD4 Cell Counts Had Risen to More Than 200 per Cubic Millimeter.Figure 2
Kaplan–Meier Curves Showing the Probability of a Decline in the CD4 Cell Count to Less Than 200 per Cubic Millimeter and the Probability of Reinstitution of Secondary Prophylaxis against P. carinii.Article Activity
- Article
The life expectancy of patients with human immunodeficiency virus (HIV) infection has dramatically improved,1-4 and the risk of opportunistic infections, including Pneumocystis carinii pneumonia, has markedly declined in industrialized countries since 19961,5 because of the widespread use of highly active antiretroviral therapy. This decline has suggested that highly active antiretroviral therapy results in clinically important immune reconstitution. The absolute risk of the progression of HIV disease was markedly lower in patients who had an increase in CD4 cell counts in peripheral blood to more than 200 per cubic millimeter than in patients who had no such increase.6 The degree of protection conferred could have been overestimated in these studies, because the majority of patients continued to use standard prophylactic medication against various opportunistic infections, including P. carinii pneumonia. However, several studies have subsequently indicated that the reduction in the risk of primary P. carinii pneumonia is maintained after the discontinuation of specific chemoprophylaxis.7-10 These findings resulted in recommendations for the discontinuation of primary prophylaxis against P. carinii pneumonia in patients who have a response to antiretroviral therapy.11
The risk of recurrence of P. carinii pneumonia is substantially higher than the risk of primary P. carinii pneumonia.12 This increase in risk is almost certainly due to the fact that the immune system is more profoundly compromised in patients in whom pneumonia has already developed, and to the presence of residual P. carinii organisms in the lungs despite a clinical response to therapy.13 Thus, recommendations regarding the safety of discontinuing primary prophylaxis cannot simply be extrapolated to the discontinuation of secondary prophylaxis.
We therefore analyzed data on eight European cohorts of HIV-infected patients who had been successfully treated for an episode of P. carinii pneumonia, whose CD4 cell count had risen to more than 200 per cubic millimeter, and who subsequently discontinued chemoprophylaxis against recurrent P. carinii pneumonia.
Methods
Participating Cohort Studies
Our analysis included data from eight large prospective European cohort studies (Table 1Table 1
Cohorts Included in the Study.), all of which have been approved by local ethics committees, use standardized methods of data collection, and schedule follow-up visits at least once every six months. Additional measurements of peripheral-blood CD4 cell counts and plasma levels of HIV type 1 (HIV-1) RNA, determined at the time of routine evaluations at the 162 participating clinics, are also recorded. One of the eight studies, the EuroSIDA study, is a multicenter study and may include patients who are also members of the other cohorts. Therefore, each of the other cohort studies verified that none of its patients were also enrolled in the EuroSIDA study.Inclusion and Exclusion Criteria
We included patients with HIV-1 infection who had previously been given a definitive or presumptive diagnosis of P. carinii pneumonia and had received secondary prophylaxis against recurrent pneumonia, which was discontinued between October 1996 and January 2000, during highly active antiretroviral treatment after their CD4 cell counts had risen to more than 200 per cubic millimeter. The decision to discontinue prophylaxis was the result of consultation between individual patients and their physicians and reflected the assumption that the increased CD4 cell counts induced by highly active antiretroviral therapy were indeed clinically protective. In some countries, discontinuation of secondary prophylaxis against P. carinii pneumonia was even formulated in official treatment guidelines.
Secondary prophylaxis was defined as treatment with any drug with known activity against P. carinii or Toxoplasma gondii and included trimethoprim–sulfamethoxazole, inhaled pentamidine, dapsone, pyrimethamine, and atovaquone. Highly active antiretroviral therapy was defined as therapy with at least one protease inhibitor or non–nucleoside-analogue reverse-transcriptase inhibitor in combination with at least two nucleoside-analogue reverse-transcriptase inhibitors. Patients whose CD4 cell counts for the six months preceding the discontinuation of secondary prophylaxis were unavailable and patients who were unavailable for follow-up were excluded from the analysis.
End Points
Recurrence of P. carinii pneumonia, diagnosed definitively or presumptively, after the discontinuation of secondary prophylaxis was the primary end point of the study. A diagnosis was considered definitive if P. carinii was found on microscopical analysis of induced sputum or bronchoalveolar-lavage fluid or on histologic examination of a specimen of lung tissue. The diagnosis of P. carinii pneumonia was considered presumptive if results from invasive pulmonary diagnostic procedures were not available. At a minimum, a presumptive diagnosis required a recent history of dyspnea on exertion or nonproductive cough, an appropriate response to any of the standard recommended treatments for P. carinii pneumonia, and the absence of evidence of bacterial pneumonia.
The secondary end points of the study were bacterial pneumonia, death or any new illness classified as defining the acquired immunodeficiency syndrome (AIDS), CD4 cell counts of less than 200 per cubic millimeter, and reinstitution of secondary prophylaxis — all occurring after the discontinuation of secondary prophylaxis. A diagnosis of bacterial pneumonia required documentation of a compatible clinical history, including an acute onset of pulmonary symptoms, and typical pulmonary infiltrates on a chest radiograph, together with a response to antibacterial drugs with no known activity against P. carinii. Furthermore, most study groups performed a careful retrospective chart review of all patients to identify single episodes of bacterial pneumonia and to confirm the other study end points.
Statistical Analysis
Patient selection and data extraction were performed at the data centers of the participating cohort studies. Data on a predefined set of anonymous demographic, laboratory, and clinical variables from the selected patients were then pooled and analyzed centrally. Follow-up was measured from the date of discontinuation of secondary prophylaxis against P. carinii pneumonia until the date of the last clinical follow-up, the date of reinitiation of secondary prophylaxis, or the date of diagnosis of recurrent P. carinii pneumonia. In a separate analysis, follow-up was restricted to the periods when CD4 cell counts remained at or above 200 per cubic millimeter. The closing date for the analysis was April 19, 2000. Recurrent cases of P. carinii pneumonia and bacterial pneumonia were assumed to have a Poisson distribution, and exact confidence intervals were calculated for the incidence. The length of time to the documentation of a CD4 cell count of less than 200 per cubic millimeter and the length of time to the reinitiation of secondary prophylaxis were analyzed by the Kaplan–Meier method. All reported P values are two-sided. We used Stata software (version 6.0, Stata, College Station, Tex.) for statistical analyses.
Results
A total of 325 patients fulfilled the inclusion criteria. Their characteristics at the time of the discontinuation of secondary prophylaxis against P. carinii pneumonia are shown in Table 2Table 2
Characteristics of the 325 Study Patients at the Discontinuation of Secondary Prophylaxis and CD4 Cell Counts at the End of the Study.. The median age was 38 years, and 85 percent of the patients were men. The median CD4 cell count at the time secondary prophylaxis was discontinued was 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. Highly active antiretroviral therapy included a single protease inhibitor and two nucleoside-analogue reverse-transcriptase inhibitors in 74 percent of the patients. Two protease inhibitors or a non–nucleoside-analogue reverse-transcriptase inhibitor, together with at least two nucleoside-analogue reverse-transcriptase inhibitors, were used in 17 percent and 9 percent of patients, respectively.CD4 Cell Dynamics
The evolution of CD4 cell counts from the diagnosis of P. carinii pneumonia to the start of highly active antiretroviral therapy, the discontinuation of secondary prophylaxis, and the last available CD4 cell count are shown in Figure 1Figure 1
Evolution of CD4 Cell Counts in 325 Patients with HIV Infection and a History of P. carinii Pneumonia in Whom Highly Active Antiretroviral Therapy Was Initiated and Secondary Prophylaxis Was Subsequently Discontinued after CD4 Cell Counts Had Risen to More Than 200 per Cubic Millimeter.. The median increase in CD4 cell counts from the nadir to the value at the time secondary prophylaxis was discontinued was 283 per cubic millimeter. After secondary prophylaxis was discontinued, the CD4 cell counts increased further by a median of 50 per cubic millimeter, but in 27 patients (8 percent) they dropped to less than 200 per cubic millimeter (Table 3Table 3
Characteristics of the 325 Study Patients during Follow-up.). The probability that a patient would have a CD4 cell count of less than 200 per cubic millimeter 12 and 24 months after secondary prophylaxis was discontinued was 8 percent (95 percent confidence interval, 5 to 12 percent) and 14 percent (95 percent confidence interval, 9 to 23 percent), respectively. In 20 (74 percent) of the 27 patients whose CD4 cell counts fell to less than 200 per cubic millimeter after discontinuation of secondary prophylaxis, the last available CD4 count (after a median of eight months) was again well above 200 cells per cubic millimeter, with a median of 316 cells per cubic millimeter.Incidence of Events during Follow-up
No diagnoses of recurrent P. carinii pneumonia were recorded during 374 person-years of follow-up in the absence of secondary prophylaxis (Table 3). The incidence was therefore 0, with an upper 99 percent confidence limit of 1.2 per 100 person-years of follow-up. For 355 person-years of follow-up, CD4 cell counts were at or above 200 per cubic millimeter, resulting in an upper 99 percent confidence limit of 1.3 per 100 person-years.
One patient decided to stop highly active antiretroviral therapy but resumed secondary prophylaxis; in this patient, a presumptive diagnosis of P. carinii pneumonia with a CD4 cell count of 12 per cubic millimeter was made six months later. Five patients had a new AIDS-defining illness, and four patients died during follow-up. A diagnosis of bacterial pneumonia was made in 7 of the 222 patients from the seven cohorts that had collected this information.
Reinstitution of Secondary Prophylaxis
Fifteen of 325 patients (5 percent) began secondary prophylaxis again during follow-up, including 11 patients whose CD4 cell counts remained above 200 per cubic millimeter (Figure 2Figure 2
Kaplan–Meier Curves Showing the Probability of a Decline in the CD4 Cell Count to Less Than 200 per Cubic Millimeter and the Probability of Reinstitution of Secondary Prophylaxis against P. carinii.). For most of these 11 patients, the reason for the reinstitution of secondary prophylaxis was a decline in CD4 cell counts, which frequently occurred in conjunction with incomplete control of HIV replication.Discussion
This study supports the hypothesis that the CD4 cell recovery associated with highly active antiretroviral therapy leads to profoundly improved protection against opportunistic infections that are common in patients with HIV infection who have low CD4 cell counts.20,21 If CD4 cell recovery were not associated with protection against recurrent P. carinii pneumonia, we would have expected — on the basis of historical data — that more than 50 percent of the patients would have a relapse of P. carinii pneumonia during follow-up.12 However, P. carinii pneumonia did not develop in any of the patients after secondary prophylaxis was discontinued.
Several studies have previously addressed this issue, with similar results,7,8,10,22 but none of these studies were conclusive, given their small samples and hence their wide confidence intervals. The upper 99 percent confidence limit of the incidence of P. carinii pneumonia in the present study was only 1.2 cases per 100 person-years of follow-up. Thus, although we cannot exclude the possibility that P. carinii pneumonia may develop in patients who discontinue secondary prophylaxis, the risk is very low. Similarly, although a relatively low risk of a primary episode of P. carinii pneumonia was found in patients with CD4 cell counts above 200 per cubic millimeter,9,23-25 the threshold CD4 cell count for instituting primary prophylaxis was set at 200 per cubic millimeter.26 Guidelines for the initiation or discontinuation of prophylaxis (which define the group of patients in whom it is not needed) will always be based on the evaluation not only of the relative benefits but also of the risks of the prophylactic treatment. Potential problems associated with prophylaxis are diverse and drug-specific and include hypersensitivity to sulfonamides,27,28 the development of drug-resistant P. carinii 29,30 and bacteria,31 the high cost (especially of inhaled pentamidine32 and atovaquone33), and the number of additional pills that must be taken.
A particular concern regarding the discontinuation of trimethoprim–sulfamethoxazole is the loss of protection against common bacterial infections.34 In this study, the incidence of bacterial pneumonia after the discontinuation of secondary prophylaxis against P. carinii pneumonia was only 2.7 episodes per 100 person-years of follow-up. This rate is considerably lower than was reported in a study undertaken before highly active antiretroviral therapy became available,35 despite the fact that we used quite liberal criteria to identify possible cases of bacterial pneumonia. However, we cannot rule out the possibility that patients who are at higher risk for bacterial pneumonia might benefit from antibacterial chemoprophylaxis, such as may be provided by continued use of trimethoprim–sulfamethoxazole. We also did not observe any cases of cerebral toxoplasmosis, an infection that may also be prevented by prophylaxis against P. carinii pneumonia.36
Most patients in this study had been taking combination antiretroviral-drug therapy for more than one year before prophylaxis was discontinued. Thus, their physicians apparently were concerned about discontinuing secondary prophylaxis prematurely, since P. carinii pneumonia is a severe infection associated with a 10 to 15 percent case fatality rate.25,37 Therefore, caution should be exercised in extrapolating our findings to persons who have smaller increases in CD4 cell counts or have been treated for shorter periods with highly active antiretroviral therapy.
Our study does not directly address the question of when secondary prophylaxis should be restarted, but it does provide some clues. Almost 10 percent of all patients had a decrease in the CD4 cell counts to less than 200 per cubic millimeter, a threshold below which prophylaxis against P. carinii pneumonia is generally recommended.11 As compared with the remaining patients, those in whom secondary prophylaxis against P. carinii pneumonia was reinstituted or whose CD4 cell counts decreased to less than 200 per cubic millimeter already had lower CD4 cell counts when secondary prophylaxis was discontinued (data not shown). Thus, patients who discontinue secondary prophylaxis against P. carinii pneumonia when their CD4 cell counts are marginally above 200 per cubic millimeter, particularly if they have subsequent negative trends in their CD4 cell counts or evidence of increased HIV replication, should be carefully monitored for decreases in CD4 cell counts to less than 200 per cubic millimeter and hence the need for reinstitution of secondary prophylaxis.
Several limitations of our study should be noted. First, it was not a controlled clinical trial but a compilation of data from several observational cohorts; there may have been undetected differences between the cohorts. However, clinical suspicion and diagnosis of P. carinii pneumonia are an integral part of routine care at the sites participating in this study, and it is unlikely that any cases of P. carinii pneumonia remained undiagnosed. Most of the cases of P. carinii pneumonia in this study (83 percent) were definitively diagnosed on the basis of microscopy rather than clinical suspicion. All the studies have well-implemented quality-control procedures to ensure the correct transfer of data from patients' records to the cohort data base. Although our study was not randomized, such a design would not have improved the interpretability of the findings, since no case of recurrent P. carinii pneumonia was diagnosed.
In conclusion, as has been demonstrated for primary prophylaxis, secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients with HIV infection who have had a response to highly active antiretroviral therapy (indicated by a CD4 cell count above 200 per cubic millimeter) with a minimal risk of recurrent P. carinii pneumonia.
Presented in part at the 7th Conference on Retroviruses and Opportunistic Infections, January 30–February 2, 2000, San Francisco.
The EuroSIDA study was supported by grants from the European Commission BIOMED 1 (CT94-1637) and BIOMED 2 (CT97-2713) programs, from Pharmacia & Upjohn, Glaxo Wellcome, Roche, and Merck, and from the Swiss Federal Office for Education and Science (for the Swiss sites). The Swiss HIV Cohort Study was supported by a grant (3345-062041) from the Swiss National Science Foundation. The ATHENA study was supported by a grant (CURE/97-46486) from the Health Insurance Fund Council, Amstelveen, the Netherlands. The Frankfurt HIV Cohort was supported by a grant from the Bundesministerium für Bildung und Forschung and Glaxo Wellcome Research. The ICONA network was supported by an unrestricted educational grant from Glaxo Wellcome, Italy.
Source Information
From the Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland (B.L.); the Royal Free and University College Medical School, London (A.M.); the Division of Infectious Diseases, Tropical Medicine, and AIDS and the National AIDS Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, Amsterdam (P.R.); the Division of Infectious Diseases, University Hospital Bern, Bern, Switzerland (H.F.); the Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark (O.K., J.D.L.); the Center of Internal Medicine, J.W. Goethe University, Frankfurt, Germany (M.B.); the Infectious Diseases Department, San Raffaele Hospital, Milan, Italy (C.U.-F.); the Tropical and Infectious Diseases Department, Hôpital l'Archet, Nice, France (C.P.); the Institute of Infectious and Tropical Diseases, University of Milan, Milan, Italy (A.d'A.M.); and the Department of Internal Medicine, Division of Infectious Diseases and AIDS, University Medical Center Utrecht, Utrecht, the Netherlands (M.M.E.S.).
Address reprint requests to Dr. Ledergerber at the Division of Infectious Diseases, University Hospital, CH-8091 Zurich, Switzerland, or at infled@usz.unizh.ch.
Members of the study groups are listed in the Appendix.
Appendix
The members of the eight study groups were as follows: The Multicenter Study Group on EuroSIDA — Austria: N. Vetter (national coordinator), Vienna; Belgium: N. Clumeck (national coordinator), P. Hermans, B. Sommereijns, Brussels; R. Colebunders, Antwerp; Czech Republic: L. Machala (national coordinator), H. Rozsypal, Prague; Denmark: J. Nielsen (national coordinator), T. Benfield, T. Katzenstein, B. Røge, P. Skinhøj, Copenhagen; France: C. Katlama (national coordinator), C. Rivière, J.-P. Viard, Paris; T. Saint-Marc, P. Vanhems, Lyons; Germany: M. Dietrich (national coordinator), C. Manegold, J. van Lunzen, Hamburg; V. Miller, S. Staszewski, Frankfurt; F.-D. Goebel, Munich; B. Salzberger, Cologne; J. Rockstroh, Bonn; Greece: J. Kosmidis (national coordinator), P. Gargalianos, H. Sambatakou, G. Panos, G. Boulmetis, M. Astriti, Athens; Hungary: D. Banhegyi (national coordinator), Budapest; Ireland: F. Mulcahy (national coordinator), Dublin; Israel: I. Yust (national coordinator), D. Turner, Tel Aviv; S. Pollack, Z. Ben-Ishai, Haifa; Z. Bentwich, Rehovot; S. Maayan, Jerusalem; Italy: S. Vella and A. Chiesi (national coordinators), V. Vullo, P. Santopadre, C. Arici, P. Franci, P. Narciso, A. Antinori, M. Zaccarelli, Rome; F. Suter, A. Cremaschi, Bergamo; R. Pristerá, Bolzano; F. Vichi, Florence; B. DeRienzo, A. Bedini, Modena; A. Chirianni, E. Montesarchio, Naples; R. Finazzi, Milan; Luxemburg: R. Hemmer (national coordinator), T. Staub, Luxemburg; the Netherlands: J. Wubbels, Amsterdam; Norway: J. Bruun (national coordinator), A. Maeland, Oslo; Poland: B. Knysz (national coordinator), J. Gasiorowski, Wroclaw; A. Horban, Warsaw; R. Rogowska-Szadkowska, Bialystok; A. Boron-Kaczmarska, Szczecin; M. Beniowski, Chorzow; H. Trocha, Gdansk; Portugal: F. Antunes (national coordinator), K. Mansinho, R. Proenca, Lisbon; Spain: J. González-Lahoz (national coordinator), R. Polo, V. Soriano, Madrid; B. Clotet, A. Jou, J. Conejero, C. Tural, Badalona; J. Gatell, J. Miró, Barcelona; Sweden: A. Blaxhult (national coordinator), B. Heidemann, P. Pehrson, Stockholm; Switzerland: V. Soravia-Dunand, Geneva; United Kingdom: S. Barton (national coordinator), A. Johnson, D. Mercey, A. Phillips, C. Loveday, M. Johnson, A. Pinching, J. Parkin, J. Weber, G. Scullard, London; M. Fisher, Brighton; R. Brettle, Edinburgh; AIDS Therapy Evaluation Project Netherlands — W. Bronsveld, Alkmaar; H. Weigel, K. Brinkman, P. Frissen, J. ten Veen, M. Hillebrand, S. Schieveld, J. Mulder, E. van Gorp, P. Meenhorst, A. van Eeden, F. Claessen, R. Perenboom, S. Danner, J.K. Eeftinck Schattenkerk, E. Gisolf, M. Godfried, M. Jambroes, J. Lange (study coordinator), J. van der Meer, J. Nellen, D. Notermans, N. Pakker, T. van der Poll, M. van Praag, J. Prins, M. Reijers, T. Ruys, M. van der Valk, E. van der Ven, A. Verbon, G.J. Weverling, F. Wit, F. de Wolf (study coordinator), J. Wubbels, Amsterdam; C. Richter, Arnhem; R. Vriesendorp, R. Kauffman, E. Kogger, The Hague; B. Bravenboer, Eindhoven; C. ten Napel, K. Pogany, Enschede; H.G. Sprenger, G. Law, Groningen; R.W. ten Kate, Haarlem; M. Leemhuis, Leeuwarden; F. Kroon, Leiden; G. Schrey, S. van der Geest, A. van der Ven, Maastricht; P. Koopmans, M. Keuter, D. Telgt, Nijmegen; M. van der Ende, I. Gyssens, S. de Marie, Rotterdam; J. Juttman, C. van der Heul, Tilburg; J. Borleffs, I. Hoepelman, C. Jaspers, K. Schurink, Utrecht; W. Blok, Vlissingen; Swiss HIV Cohort Study — M. Battegay, H. Bucher, P. Erb, T. Klimkait, C. Rudin, Basel; M. Gorgievski, Bern; M. Egger, Bristol, United Kingdom; B. Hirschel, L. Perrin, V. Schiffer, Geneva; P. Bürgisser, P. Francioli (study coordinator), F. Paccaud, G. Pantaleo, P. Sudre, M. Rickenbach, A. Telenti, Lausanne; E. Bernasconi, J.C. Piffaretti, Lugano; R. Amiet, W. Fierz, C. Kind, P. Vernazza, St. Gall; M. Flepp, H. Günthard, M. Opravil, P. Grob, U. Lauper, J. Schupbach, R. Weber, Zurich; Danish Cohort of Patients Stopping Prophylaxis — J. Gerstoft, Copenhagen; N. Obel, Aarhus; H. Nielsen, Aalborg; C. Pedersen, Odense; Frankfurt HIV Cohort — S. Staszewski, V. Miller, E. Helm, Frankfurt, Germany; HSR Cohort — A. Lazzarin, Milan, Italy; DMI-2 Study Group at Nice University Hospital — P. Dellamonica, P.M. Roger, J.P. Cassuto, A. Pesce, J.G. Fuzibet, F. Sanderson, Y. Le Fichoux, J. Cottalorda, J.F. Michiels, Nice, France; Italian Cohort of Patients Naive to Antiretrovirals — M. Montroni, G. Scalise, A. Costantini, M.S. Del Prete, Ancona; U. Tirelli, G. Nasti, Aviano; G. Angarano, L.M. Perulli, Bari; F. Suter, C. Arici, Bergamo; F. Chiodo, F.M. Gritti, V. Colangeli, C. Fiorini, L. Guerra, Bologna; G. Carosi, G.P. Cadeo, F. Castelli, C. Minardi, D. Vangi, Brescia; S. Caprioli, G. Migliorino, Busto Arsizio; P.E. Manconi, P. Piano, Cagliari; T. Ferraro, L. Cosco, Catanzaro; E. Pizzigallo, F. Ricci, Chieti; G.M. Vigevani, L. Pusterla, Como; G. Carnevale, A. Pan, Cremona; P. Viganò, G.C. Ghiselli, Cuggiono; F. Ghinelli, L. Sighinolfi, Ferrara; F. Leoncini, F. Mazzotta, S. Ambu, S. Lo Caputo, Florence; B. Grisorio, S. Ferrara, Foggia; P. Grima, P. Tundo, Galatina; G. Pagano, N. Piersantelli, A. Alessandrini, R. Piscopo, Genoa; M. Toti, S. Chigiotti, Grosseto; F. Soscia, L. Tacconi, Latina; A. Orani, G. Castaldo, Lecco; A. Scasso, A. Vincenti, Lucca; A. Scalzini, F. Alessi, Mantua; M. Moroni (study coordinator), A. Lazzarin, A. Cargnel, F. Milazzo, L. Caggese, V. Testori, F. Delfanti, B. Carini, B. Adriani, S. Garavaglia, C. Moioli, Milan; R. Esposito, C. Mussini, Modena; N. Abrescia, A. Chirianni, O. Perrella, M. Piazza, M. DeMarco, V. Montesarchio, E. Manzillo, S. Nappa, Naples; P. Cadrobbi, R. Scaggiante, Padua; A. Colomba, T. Prestileo, Palermo; G. Filice, L. Minoli, F.A. Patruno Savino, R. Maserati, Pavia; S. Pauluzzi, A. Tosti, Perugia; F. Alberici, M. Sisti, Piacenza; F. Menichetti, A. Smorfa, Pisa; C. De Stefano, A. La Gala, Potenza; T. Zauli, G. Ballardini, Ravenna; L. Bonazzi, M.A. Ursitti, Reggio Emilia; R. Ciammarughi, M. Arlotti, Rimini; L. Ortona, F. Dianzani, A. Antinori, G. Antonucci, S. D'Elia, G. Ippolito, P. Narciso, N. Petrosillo, G. Rezza, V. Vullo, A. De Luca, A. Del Forno, M.R. Capobianchi, M. Zaccarelli, P. De Longis, M. Ciardi, E. Girardi, G. D'Offizi, F. Palmieri, P. Pezzotti, M. Lichter, Rome; M.S. Mura, M. Mannazzu, Sassari; P. Caramello, A. Sinicco, M.L. Soranzo, D. Giacobbi, M. Sciandra, B. Salassa, Turin; D. Torre, Varese; A. Poggio, G. Bottari, Verbania; E. Raise, S. Pasquinucci, Venice; F. De Lalla, G. Tositti, Vicenza; F. Resta, A. Chimienti, Taranto; A. Cozzi Lepri, London, United Kingdom.
- References
References
1
Palella FJ Jr ,Delaney KM ,Moorman AC , et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998;338:853-860
Full Text | Web of Science | Medline2
Egger M ,Hirschel B ,Francioli P , et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study: Swiss HIV Cohort Study. BMJ 1997;315:1194-1199
CrossRef | Web of Science | Medline3
Mocroft A ,Vella S ,Benfield TL , et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998;352:1725-1730
CrossRef | Web of Science | Medline4
Ledergerber B ,Egger M ,Opravil M , et al. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study: Swiss HIV Cohort Study. Lancet 1999;353:863-868
CrossRef | Web of Science | Medline5
Ledergerber B ,Egger M ,Erard V , et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA 1999;282:2220-2226
CrossRef | Web of Science | Medline6
Miller V ,Mocroft A ,Reiss P , et al. Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study. Ann Intern Med 1999;130:570-577
Web of Science | Medline7
Schneider MM ,Borleffs JC ,Stolk RP ,Jaspers CA ,Hoepelman AI . Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1-infected patients treated with highly active antiretroviral therapy. Lancet 1999;353:201-203
CrossRef | Web of Science | Medline8
Weverling GJ ,Mocroft A ,Ledergerber B , et al. Discontinuation of Pneumocystis carinii pneumonia after start of highly active antiretroviral therapy in HIV-1 infection. Lancet 1999;353:1293-1298
CrossRef | Web of Science | Medline9
Furrer H ,Egger M ,Opravil M , et al. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. N Engl J Med 1999;340:1301-1306
Full Text | Web of Science | Medline10
Kirk O ,Lundgren JD ,Pedersen C ,Nielsen H ,Gerstoft J . Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy? AIDS 1999;13:1647-1651
CrossRef | Web of Science | Medline11
1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: U.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA). MMWR Morb Mortal Wkly Rep 1999;48:1-59, 61
Medline12
Montaner JS ,Lawson LM ,Gervais A , et al. Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia: a randomized, placebo-controlled study. Ann Intern Med 1991;114:948-953
Web of Science | Medline13
Shelhamer JH ,Ognibene FP ,Macher AM , et al. Persistence of Pneumocystis carinii in lung tissue of acquired immunodeficiency syndrome patients treated for pneumocystis pneumonia. Am Rev Respir Dis 1984;130:1161-1165
Web of Science | Medline14
Lundgren JD ,Phillips AN ,Vella S , et al. Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1997;16:153-160
CrossRef | Medline15
Ledergerber B ,von Overbeck J ,Egger M ,Luthy R . The Swiss HIV Cohort Study: rationale, organization and selected baseline characteristics. Soz Praventivmed 1994;39:387-394
CrossRef | Medline16
Brodt HR ,Kamps BS ,Gute P ,Knupp B ,Staszewski S ,Helm EB . Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy. AIDS 1997;11:1731-1738
CrossRef | Web of Science | Medline17
Rizzardi GP ,Lazzarin A ,Musicco M , et al. Risks and benefits of aerosolized pentamidine and cotrimoxazole in primary prophylaxis of Pneumocystis carinii pneumonia in HIV-1-infected patients: a two-year Italian multicentric randomized controlled trial. J Infect 1996;32:123-131
CrossRef | Web of Science | Medline18
Pradier C ,Pesce A ,Taillan B ,Roger PM ,Bentz L ,Dellamonica P . Reducing the incidence of Pneumocystis carinii pneumonia: a persisting challenge. AIDS 1997;11:832-833
Web of Science | Medline19
d'Arminio Monforte A ,Lepri AC ,Rezza G , et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. AIDS 2000;14:499-507
CrossRef | Web of Science | Medline20
Phillips AN ,Lee CA ,Elford J , et al. Serial CD4 lymphocyte counts and development of AIDS. Lancet 1991;337:389-392
CrossRef | Web of Science | Medline21
Mocroft AJ ,Lundgren JD ,d'Arminio Monforte A , et al. Survival of AIDS patients according to type of AIDS-defining event. Int J Epidemiol 1997;26:400-407
CrossRef | Web of Science | Medline22
Soriano V ,Dona C ,Rodriguez-Rosado R ,Barreiro P ,Gonzales-Lahoz J . Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy. AIDS 2000;14:383-386
CrossRef | Web of Science | Medline23
Phair J ,Munoz A ,Detels R , et al. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. N Engl J Med 1990;322:161-165
Full Text | Web of Science | Medline24
Masur H ,Ognibene FP ,Yarchoan R , et al. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med 1989;111:223-231
Web of Science | Medline25
Lundgren JD ,Barton SE ,Lazzarin A , et al. Factors associated with the development of Pneumocystis carinii pneumonia in 5,025 European patients with AIDS. Clin Infect Dis 1995;21:106-113
CrossRef | Web of Science | Medline26
Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 1992;41:1-11
Medline27
Bozzette SA ,Finkelstein DM ,Spector SA , et al. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995;332:693-699
Full Text | Web of Science | Medline28
Hardy WD ,Feinberg J ,Finkelstein DM , et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: AIDS Clinical Trials Group protocol 021. N Engl J Med 1992;327:1842-1848
Full Text | Web of Science | Medline29
Mei Q ,Gurunathan S ,Masur H ,Kovacs JA . Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in dihydropteroate synthase gene. Lancet 1998;351:1631-1632
CrossRef | Web of Science | Medline30
Helweg-Larsen J ,Benfield TL ,Eugen-Olsen J ,Lundgren JD ,Lundgren B . Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia. Lancet 1999;354:1347-1351
CrossRef | Web of Science | Medline31
Rodriguez-Barradas MC ,Tharapel RA ,Groover JE , et al. Colonization by Streptococcus pneumoniae among human immunodeficiency virus-infected adults: prevalence of antibiotic resistance, impact of immunization, and characterization by polymerase chain reaction with BOX primers of isolates from persistent S. pneumoniae carriers. J Infect Dis 1997;175:590-597
CrossRef | Web of Science | Medline32
Hirschel B ,Lazzarin A ,Chopard P , et al. A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia. N Engl J Med 1991;324:1079-1083
Full Text | Web of Science | Medline33
El-Sadr WM ,Murphy RL ,Yurik TM , et al. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. N Engl J Med 1998;339:1889-1895
Full Text | Web of Science | Medline34
Navin TR ,Rimland D ,Lennox JL , et al. Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus. J Infect Dis 2000;181:158-164
CrossRef | Web of Science | Medline35
Hirschtick RE ,Glassroth J ,Jordan MC , et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus. N Engl J Med 1995;333:845-851
Full Text | Web of Science | Medline36
Carr A ,Tindall B ,Brew BJ , et al. Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS. Ann Intern Med 1992;117:106-111
Web of Science | Medline37
Benfield TL ,Vestbo J ,Junge J ,Nielsen TL ,Jensen AB ,Lundgren JD . Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 1995;151:1058-1062
Web of Science | Medline
- Citing Articles (62)
Citing Articles
1
DH Dockrell, R Breen, M Lipman, RF Miller. (2011) 3 Pulmonary opportunistic infections. HIV Medicine 12, 25-42
CrossRef2
David H. Dockrell, Simon Edwards, Martin Fisher, Ian Williams, Mark Nelson. (2011) Evolving controversies and challenges in the management of opportunistic infections in HIV-seropositive individuals. Journal of Infection
CrossRef3
, F. Schoeni-Affolter, B. Ledergerber, M. Rickenbach, C. Rudin, H. F. Gunthard, A. Telenti, H. Furrer, S. Yerly, P. Francioli. (2010) Cohort Profile: The Swiss HIV Cohort Study. International Journal of Epidemiology 39:5, 1179-1189
CrossRef4
, C. Giaquinto, M. Penazzato, R. Rosso, S. Bernardi, O. Rampon, P. Nasta, A. Ammassari, A. Antinori, R. Badolato, G. Castelli Gattinara, A. d’Arminio Monforte, M. De Martino, A. De Rossi, P. Di Gregorio, S. Esposito, F. Fatuzzo, S. Fiore, A. Franco, C. Gabiano, L. Galli, O. Genovese, V. Giacomet, A. Giannattasio, C. Gotta, A. Guarino, A. Martino, F. Mazzotta, N. Principi, M. B. Regazzi, P. Rossi, R. Russo, M. Saitta, F. Salvini, S. Trotta, A. Viganò, G. Zuccotti, G. Carosi. (2010) Italian consensus statement on paediatric HIV infection. Infection 38:4, 301-319
CrossRef5
AS Walker, D Ford, CF Gilks, P Munderi, F Ssali, A Reid, E Katabira, H Grosskurth, P Mugyenyi, J Hakim, JH Darbyshire, DM Gibb, AG Babiker. (2010) Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort. The Lancet 375:9722, 1278-1286
CrossRef6
Yukiko Komano, Masayoshi Harigai, Ryuji Koike, Haruhito Sugiyama, Jun Ogawa, Kazuyoshi Saito, Naoya Sekiguchi, Masayuki Inoo, Ikuko Onishi, Hiroyuki Ohashi, Fujio Amamoto, Masayuki Miyata, Hideo Ohtsubo, Kazuko Hiramatsu, Masahiro Iwamoto, Seiji Minota, Naoki Matsuoka, Goichi Kageyama, Kazuyoshi Imaizumi, Hitoshi Tokuda, Yasumi Okochi, Koichiro Kudo, Yoshiya Tanaka, Tsutomu Takeuchi, Nobuyuki Miyasaka. (2009) Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case-control study of 21 patients. Arthritis & Rheumatism 61:3, 305-312
CrossRef7
José M. Miró. (2008) Prevención de las infecciones oportunistas en pacientes adultos y adolescentes infectados por el VIH en el año 2008. Enfermedades Infecciosas y Microbiología Clínica 26:7, 437-464
CrossRef8
S Grabar, E Lanoy, C Allavena, M Mary-Krause, M Bentata, P Fischer, A Mahamat, C Rabaud, D Costagliola, . (2008) Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy. HIV Medicine 9:4, 246-256
CrossRef9
Babafemi O. Taiwo, Robert L. Murphy. (2008) Clinical applications and availability of CD4+ T cell count testing in sub-Saharan Africa. Cytometry Part B: Clinical Cytometry 74B:S1, S11-S18
CrossRef10
Harigai, Masayoshi, Koike, Ryuji, Miyasaka, Nobuyuki, . (2007) Pneumocystis Pneumonia Associated with Infliximab in Japan. New England Journal of Medicine 357:18, 1874-1876
Full Text11
Gianni E D??Egidio, Stephen Kravcik, Curtis L Cooper, D William Cameron, Dean A Fergusson, Jonathan B Angel. (2007) Pneumocystis jiroveci pneumonia prophylaxis is not required with a CD4+ T-cell count < 200 cells/??l when viral replication is suppressed. AIDS 21:13, 1711-1715
CrossRef12
Munir Pirmohamed, Nicola S Drummond, Dean J Naisbitt, B Kevin Park. (2007) Drug hypersensitivity reactions in patients with HIV disease. Expert Review of Clinical Immunology 3:3, 395-410
CrossRef13
Deepa G. Lazarous, Anne E. O’Donnell. (2007) Pulmonary infections in the HIV-infected patient in the era of highly active antiretroviral therapy: An update. Current Infectious Disease Reports 9:3, 228-232
CrossRef14
Olivier Lortholary, Gwendoline Poizat, Valérie Zeller, Ségolène Neuville, André Boibieux, Muriel Alvarez, Pierre Dellamonica, Françoise Botterel, Françoise Dromer, Geneviève Chêne. (2006) Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS 20:17, 2183-2191
CrossRef15
Jose M. Miro, Juan C. Lopez, Daniel Podzamczer, Jose M. Pena, Juan C. Alberdi, Esteban Martinez, Pere Domingo, Jaime Cosin, Xavier Claramonte, Jose R. Arribas, Miguel Santin, Esteban Ribera, . (2006) Discontinuation of Primary and Secondary Toxoplasma gondii Prophylaxis Is Safe in HIV‐Infected Patients after Immunological Restoration with Highly Active Antiretroviral Therapy: Results of an Open, Randomized, Multicenter Clinical Trial. Clinical Infectious Diseases 43:1, 79-89
CrossRef16
H.-Y. Sun, M.-Y. Chen, C.-F. Hsiao, S.-M. Hsieh, C.-C. Hung, S.-C. Chang. (2006) Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy. Clinical Microbiology and Infection 12:4, 381-388
CrossRef17
Andrew N Phillips, Jens D Lundgren. (2006) The CD4 lymphocyte count and risk of clinical progression. Current Opinion in HIV and AIDS 1:1, 43-49
CrossRef18
Stephen D Lawn, Motasim Badri, Robin Wood. (2005) Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort. AIDS 19:18, 2109-2116
CrossRef19
Simon Urschel, Jose Ramos, Maria Mellado, Carlo Giaquinto, Gwenda Verweel, Tobias Schuster, Tim Niehues, Bernd Belohradsky, Uwe Wintergerst. (2005) Withdrawal of Pneumocystis jirovecii prophylaxis in HIV-infected children under highly active antiretroviral therapy. AIDS 19:18, 2103-2108
CrossRef20
B Gazzard, . (2005) British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2005). HIV Medicine 6:S2, 1-61
CrossRef21
I Perbost, B Malafronte, C Pradier, LDI Santo, B Dunais, E Counillon, H Vinti, P Enel, JG Fuzibet, JP Cassuto, P Dellamonica. (2005) In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection?. HIV Medicine 6:4, 232-239
CrossRef22
Stephen D Lawn, Linda-Gail Bekker, Robin Wood. (2005) How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control. AIDS 19:11, 1113-1124
CrossRef23
José M. Miró, Julián Torre-Cisneros, Asunción Moreno, Montserrat Tuset, Carmen Quereda, Montserrat Laguno, Elisa Vidal, Antonio Riveroa, Juan González, Carlos Lumbreras, José A. Iribarrena, Jesús Fortún, Antonio Rimola, Antonio Rafecas, Guillermina Barril, Marisa Crespo, Joan Colom, Jordi Vilardell, José A. Salvador, Rosa Polo, Gregorio Garrido, Lourdes Chamorro, Blanca Miranda. (2005) Documento de consenso GESIDA/GESITRA-SEIMC, SPNS y ONT sobre trasplante de órgano sólido en pacientes infectados por el VIH en España (marzo 2005). Enfermedades Infecciosas y Microbiología Clínica 23:6, 353-362
CrossRef24
C. A. Benson, J. E. Kaplan, H. Masur, A. Pau, K. K. Holmes. (2005) Treating Opportunistic Infections among HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. Clinical Infectious Diseases 40:Supplement 3, S131-S235
CrossRef25
Claudine Zellweger, Milos Opravil, Enos Bernasconi, Matthias Cavassini, Heiner C Bucher, Veronique Schiffer, Thomas Wagels, Markus Flepp, Martin Rickenbach, Hansjakob Furrer. (2004) Long-term safety of discontinuation of secondary prophylaxis against Pneumocystis pneumonia. AIDS 18:15, 2047-2053
CrossRef26
Patrick Willemot, Marina B Klein. (2004) Prevention of HIV-associated opportunistic infections and diseases in the age of highly active antiretroviral therapy. Expert Review of Anti-infective Therapy 2:4, 521-532
CrossRef27
H Green, P Hay, DT Dunn, S McCormack, . (2004) A prospective multicentre study of discontinuing prophylaxis for opportunistic infections after effective antiretroviral therapy. HIV Medicine 5:4, 278-283
CrossRef28
Hans H. Hirsch, Gilbert Kaufmann, Pedram Sendi, Manuel Battegay. (2004) Immune Reconstitution in HIV‐Infected Patients. Clinical Infectious Diseases 38:8, 1159-1166
CrossRef29
F van Leth, FWNM Wit, P Reiss, JKME Schattenkerk, ME van der Ende, MME Schneider, JW Mulder, PHJ Frissen, F de Wolf, JMA Lange. (2004) Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy. HIV Medicine 5:2, 74-81
CrossRef30
Cristina Mussini, Patrizio Pezzotti, Jose M. Miro, Esteban Martinez, Juan Carlos Lopez Bernaldo de Quiros, Paola Cinque, Vanni Borghi, Andrea Bedini, Pere Domingo, Pedro Cahn, Philippe Bossi, Andrea De Luca, Antonella d’Arminio Monforte, Mark Nelson, Nneka Nwokolo, Silvia Helou, Ricardo Negroni, Gaia Jacchetti, Spinello Antinori, Adriano Lazzarin, Andrea Cossarizza, Roberto Esposito, Andrea Antinori, Judith A. Aberg, . (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 38:4, 565-571
CrossRef31
Jay K. Kolls. (2004) HIV Immunology and new therapies. Pediatric Pulmonology 37:S26, 59-61
CrossRef32
Naimish Patel, Henry Koziel. (2004) Pneumocystis jiroveci Pneumonia in Adult Patients with AIDS. Treatments in Respiratory Medicine 3:6, 381-397
CrossRef33
(2003) British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Medicine 4:S1, 1-41
CrossRef34
K Crothers, L Huang. (2003) Recurrence of Pneumocystis carinii pneumonia in an HIV-infected patient: apparent selective immune reconstitution after initiation of antiretroviral therapy. HIV Medicine 4:4, 346-349
CrossRef35
Diego Serraino, Vincenzo Puro, Evangelo Boumis, Claudio Angeletti, Enrico Girardi, Nicola Petrosillo, Giuseppe Ippolito. (2003) Epidemiological aspects of major opportunistic infections of the respiratory tract in persons with AIDS. AIDS 17:14, 2109-2116
CrossRef36
Ferdinand W. N. M. Wit, Peter Reiss. (2003) When to start antiretroviral therapy and what to start with—a European perspective. Current Infectious Disease Reports 5:4, 349-357
CrossRef37
Donata Medaglini, Arnd Hoeveler. (2003) The European research effort for HIV/AIDS, malaria and tuberculosis. Vaccine 21, S116-S120
CrossRef38
Paul A Volberding. (2003) HIV therapy in 2003. AIDS 17, S4-S11
CrossRef39
J-L Meynard, M Guiguet, L Fonquernie, B Lefebvre, V Lalande, I Honore, M-C Meyohas, P-M Girard. (2003) Impact of highly active antiretroviral therapy on the occurrence of bacteraemia in HIV-infected patients and their epidemiologic characteristics. HIV Medicine 4:2, 127-132
CrossRef40
Cristina Mussini, Patrizio Pezzotti, Andrea Antinori, Vanni Borghi, Antonella d’Arminio Monforte, Alessandra Govoni, Andrea De Luca, Adriana Ammassari, Nicola Mongiardo, Maria Chiara Cerri, Andrea Bedini, Cristina Beltrami, Maria Alessandra Ursitti, Teresa Bini, Andrea Cossarizza, Roberto Esposito, . (2003) Discontinuation of Secondary Prophylaxis for Pneumocystis carinii Pneumonia in Human Immunodeficiency Virus–Infected Patients: A Randomized Trial by the CIOP Study Group. Clinical Infectious Diseases 36:5, 645-651
CrossRef41
Anna R Thorner, Eric S Rosenberg. (2003) Early Versus Delayed Antiretroviral Therapy in Patients with HIV Infection. Drugs 63:13, 1325-1337
CrossRef42
Véronique Bortolotti, Anne Buvé. (2002) Prophylaxis of opportunistic infections in HIV-infected adults in sub-Saharan Africa: opportunities and obstacles. AIDS 16:10, 1309-1317
CrossRef43
Olaf Degen, Jan ven Lunzen, Matthias A. Horstkotte, Ingo Sobottka, Hans-Jurgen Stellbrink. (2002) Pneumocystis carinii pneumonia after the discontinuation of secondary prophylaxis. AIDS 16:10, 1433-1434
CrossRef44
Jean T. Santamauro, Rashmi Nisha Aurora, Diane E. Stover. (2002) Pneumocystis carinii pneumonia in patients with and without HIV infection. Comprehensive Therapy 28:2, 96-108
CrossRef45
SAMUEL A. SHELBURNE, RICHARD J. HAMILL, MARIA C. RODRIGUEZ-BARRADAS, STEPHEN B. GREENBERG, ROBERT L. ATMAR, DANIEL M. MUSHER, JOSEPH C. GATHE, FEHMIDA VISNEGARWALA, BARBARA W. TRAUTNER. (2002) Immune Reconstitution Inflammatory Syndrome. Medicine 81:3, 213-227
CrossRef46
M Floridia, V Fragola, CM Galluzzo, G Giannini, MF Pirillo, M Andreotti, C Tomino, S Vella for the ISS-IP1 Study Group. (2002) HIV-related morbidity and mortality in patients starting protease inhibitors in very advanced HIV disease (CD4 count of < 50 cells/uL): an analysis of 338 clinical events from a randomized clinical trial*. HIV Medicine 3:2, 75-84
CrossRef47
Hansjakob Furrer, . (2002) Management of opportunistic infection prophylaxis in the highly active antiretroviral therapy era. Current Infectious Disease Reports 4:2, 161-174
CrossRef48
V. Zeller, C. Truffot, R. Agher, P. Bossi, R. Tubiana, E. Caumes, M. Jouan, F. Bricaire, C. Katlama. (2002) Discontinuation of Secondary Prophylaxis against Disseminated Mycobacterium avium Complex Infection and Toxoplasmic Encephalitis. Clinical Infectious Diseases 34:5, 662-667
CrossRef49
Suwat Chariyalertsak, Khuanchai Supparatpinyo, Thira Sirisanthana, Kenrad E. Nelson. (2002) A Controlled Trial of Itraconazole as Primary Prophylaxis for Systemic Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection in Thailand. Clinical Infectious Diseases 34:2, 277-284
CrossRef50
Thomas A. Trikalinos, John P. A. Ioannidis. (2001) Discontinuation of Pneumocystis carinii Prophylaxis in Patients Infected with Human Immunodeficiency Virus: A Meta‐Analysis and Decision Analysis. Clinical Infectious Diseases 33:11, 1901-1909
CrossRef51
Jay Alan Fishman. (2001) Prevention of Infection Caused by Pneumocystis carinii in Transplant Recipients. Clinical Infectious Diseases 33:8, 1397-1405
CrossRef52
(2001) British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Medicine 2:4, 276-313
CrossRef53
JD Lundgren. (2001) When to start and stop?. HIV Medicine 2:4, 229-230
CrossRef54
Lyn-li Lim, Alan C. Street, Sharon R. Lewin. (2001) Pneumocystis carinii pneumonia after cessation of secondary prophylaxis in a patient on highly active antiretroviral therapy with a CD4 cell count greater than 200/mm3. AIDS 15:14, 1912-1913
CrossRef55
Simon Urschel, Tobias Schuster, Dominik Dunsch, Uwe Wintergerst, Roland Hofstetter, Bernd H. Belohradsky. (2001) Discontinuation of primary Pneumocystis carinii prophylaxis after reconstitution of CD4 cell counts in HIV-infected children. AIDS 15:12, 1589-1591
CrossRef56
Munir Pirmohamed, B. Kevin Park. (2001) HIV and drug allergy. Current Opinion in Allergy and Clinical Immunology 1:4, 311-316
CrossRef57
Susan L. Koletar, Alison E. Heald, Dianne Finkelstein, Richard Hafner, Judith S. Currier, J. Allen McCutchan, Marc Vallee, Francesca J. Torriani, William G. Powderly, Robert J. Fass, Robert L. Murphy. (2001) A prospective study of discontinuing primary and secondary Pneumocystis carinii pneumonia prophylaxis after CD4 cell count increase to > 200 × 106/l. AIDS 15:12, 1509-1515
CrossRef58
(2001) Discontinuing Prophylaxis against Pneumocystis carinii Pneumonia. New England Journal of Medicine 344:21, 1639-1641
Full Text59
de Quiros, Juan C. Lopez Bernaldo, Miro, Jose M., Peña, Jose M., Podzamczer, Daniel, Alberdi, Juan C., Martínez, Esteban, Cosin, Jaime, Claramonte, Xavier, Gonzalez, Juan, Domingo, Pere, Casado, Jose L., Ribera, Esteban, the Grupo de Estudio del SIDA 04/98. (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 344:3, 159-167
Full Text60
Girard, Pierre-Marie, . (2001) Discontinuing Pneumocystis carinii Prophylaxis. New England Journal of Medicine 344:3, 222-223
Full Text61
&NA;. (2001) Withdrawal of primary and secondary PCP prophylaxis feasible. Inpharma Weekly &NA;:1272, 14
CrossRef62
M Pirmohamed, D J Back. (2001) The pharmacogenomics of HIV therapy. The Pharmacogenomics Journal 1:4, 243-253
CrossRef
