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Long-term follow-up of patients with AIDS treated with parenteral cidofovir for cytomegalovirus retinitis: the HPMPC Peripheral Cytomegalovirus Retinitis Trial - The Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group

Lewis, RA; Carr, LM; Doyle, K; Fainstein, V; Gross, R; Orengo-Nania, S; Samo, TC; Shigley, JW; Spencer, SS; Weinert, M; Dunn, JP; Bartlett, J; Becker, R; Feinberg, J; Jabs, DA; Johnson, DA; LaSalvia, S; Miller, T; Neisser, LG; Semba, RD; Tay-Kearney, ML; Tucker, P; Barron, B; Jarrott, C; Peyman, G; Swenie, D; Friedman, AH; Ginsburg, R; Sacks, H; Severin, C; Teich, S; Wallach, F; Rescigno, R; Cowan, J; Horan, C; Kloser, P; Wanner, M; Friedberg, DN; Addessi, A; Chachoua, A; Dieterich, D; Hill, J; Hutt, R; Ligh, J; Lorenzo-Latkany, M; Pei, M; Powers, T; Scoppe, C; Weinberg, DV; Jampol, LM; Lyon, AT; Munana, A; Murphy, R; Palella, F; Richine, L; Strugala, Z; Valadez, G; Holland, GN; Carlson, ME; Chafey, S; Hardy, WD; Johiro, AK; MacArthur-Chang, LJ; Martin, MA; Moe, AA; Strong, CA; Tufail, A; Ugalat, PS; Weisz, JM; Freeman, WR; Arevalo-Colina, JF; Clark, T; Jarman, CL; Meixner, L; Meng, TC; Spector, S; Taskintuna, I; Torriani, FJ; O'Donnell, J; Alfred, P; Ballesteros, F; Clay, D; Coleman, R; Gordon, K; Gumbley, D; Hoffman, J; Irvine, A; Jacobson, M; Larson, J; Macalalag, L; Narahara, M; Payne, M; Seiff, S; Wilson, S; Woodring, H; Davis, J; Mendez, P; Murray, T; Simmons, T; van der Horst, C; Kylstra, J; Wohl, D; Ziman, K; Pavan, PR; Bergen, GA; Cohen, SM; Craig, JA; Dehler, RL; Elbert, E; Fox, RW; Grizzard, WS; Hammer, ME; Hernandez, LS; Herrera, S; Holt, D; Kemp, S; Larkin, JA; Ledford, DK; Lockey, RF; Menosky, MM; Millard, S; Nadler, JP; Nelson, RP; Norris, D; Ormerod, LD; Pautler, SE; Poblete, SJ; Rodriguez, D; Rosenbach, KP; Seekins, DW; Toney, JR; Jabs, DA; Dodge, JM; Klemstine, JL; Schuerholtz, TA; Stevens, M; Meinert, CL; Amend-Libercci, D; Coleson, L; Collins, KL; Collison, BJ; Dawson, C; Dodge, J; Donithan, M; Ewing, C; Fink, N; Gerczak, C; Harle, J; Holbrook, JT; Huffman, R; Isaacson, MR; Gilpin, AMK; Lane, M; Levine, CR; Martin, B; Meinert, J; Nowakowski, DJ; Owens, RM; Piantadosi, B; Saah, A; Smith, M; Tonascia, J; Van Natta, ML; Davis, MD; Armstrong, J; Brickbauer, J; Brothers, R; Chop, M; Hubbard, L; Hurlburt, D; Kastorff, L; Magli, Y; Neider, M; Onofrey, J; Stoppenbach, V; Vanderhoof-Young, M; Walls, M; Hughes, R; Kurinij, N; Mowery, RL; Alston, B; Foulkes, M; Jabs, DA; Davis, MD; Kurinij, N; Meinert, CL; Mowery, RL; Jabs, DA; Addessi, A; Alston, B; Clark, T; Davis, MD; Feinberg, J; Freeman, W; Holbrook, J; Holland, GN; Hubbard, L; Jacobson, M; Kurinij, N; Lewis, RA; McArthur-Chang, L; Meinert, C; Mowery, R; Murphy, R; Polsky, B; Tonascia, J; Jabs, DA; Davis, MD; Duncan, WR; Feinberg, J; Kessler, H; Kurinij, N; Lambert, AG; Meinert, CL; Mowery, RL; Powderly, W; Schnittman, S; Spector, S; Tonascia, J; Brown, BW; Conway, B; Grizzle, J; Nussenblatt, R; Phair, JP; Smith, H; Whitley, R; Alston, B; Davis, MD; Foulkes, M; Jabs, DA; Kurinij, N; Meinert, CL; Mowery, RL; Tonascia, J; Jabs, DA; Freeman, WR; Jacobson, M; Murphy, R; Van Natta, ML; Meinert, CL; Cheng, B; Frost, K; Lambert, AG; Marco, M
Objective: To evaluate patients with cytomegalovirus (CMV) retinitis treated with intravenous cidofovir for long-term outcomes. Design: Patients with CMV retinitis enrolled in a randomized, controlled clinical trial of intravenous cidofovir as treatment for retinitis were followed for long-term outcomes, including 21 patients initially enrolled in the deferral group who received cidofovir therapy after progression of retinitis. Setting: Thirteen tertiary care clinics specializing in AIDS care and ophthalmology. Participants: Fifty-eight patients with AIDS and small peripheral CMV retinitis lesions. Interventions: Cidofovir 5 mg/kg once weekly for 2 weeks followed by low-dose maintenance cidofovir therapy (3 mg/kg) in 35 patients or high-dose maintenance (5 mg/kg) in 23 patients. Main outcome measures: Time to progression of retinitis, drug toxicities. Results: Median time to progression of retinitis was 2.5 months. Median time to discontinuation of cidofovir because of intolerance was 6.6 months, and did not differ significantly between the two maintenance doses. Median time to discontinuation of cidofovir for intolerance other than probenecid reaction was 16.3 months for patients treated with low-dose maintenance and 5.0 months for patients treated with high-dose maintenance (P = 0.021). Proteinuria of 2+ or more occurred at a rate of 1.22/person year. In patients with sufficient follow-up to determine resolution of proteinuria, 89.9% of episodes resolved, and the median time to resolution was 20 days. Rates of probenecid intolerance and of cidofovir-associated uveitis were 0.35/person-year, and 0.20/person-year, respectively
ISI:000089021600012
ISSN: 0269-9370
CID: 54539

Hepatitis C Virus/Human immunodeficiency virus coinfection: clinical management issues [In Process Citation]

Poles MA; Dieterich DT
The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized
PMID: 10913414
ISSN: 1058-4838
CID: 14719

Effect of hepatitis C virus and HIV-1 on hepatic parenchymal and mononuclear cell proliferation and apoptosis [Meeting Abstract]

Talal, AH; Yee, H; Dieterich, DT
ISI:000086783703815
ISSN: 0016-5085
CID: 54595

HIV and Hepatitis Virus Infection

Poles, MA; Dieterich, DT
As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.
PMID: 11095854
ISSN: 1523-3847
CID: 156486

Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection

Dieterich DT
The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of cirrhosis, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of interferon-alpha and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors
PMID: 10653464
ISSN: 0002-9343
CID: 11852

Patients, physicians, and clinical trials: the other side of the coins [Interview]

Abramson SB; Flexner C; Snyderman R; Dieterich DT; Korn D; Temple R; Sherwood L; Goldblatt D
PMID: 10510587
ISSN: 1081-5589
CID: 9726

Combination therapy of hepatitis B with lamivudine and famciclovir [Meeting Abstract]

Purow, JM; Weisz, K; Eison, RC; Talal, A; Dieterich, DT
ISI:000079778403471
ISSN: 0016-5085
CID: 54040

Filgrastim use for interferon induced neutropenia in patients with hepatitis C [Meeting Abstract]

Ball, LM; Sulkowski, MS; Wolf, L; Weisz, KB; Tice, AD; Dieterich, DT
ISI:000079778405145
ISSN: 0016-5085
CID: 54042

Activity of combination therapy with interferon alfa-2b plus ribavirin in chronic hepatitis C patients co-infected with HIV

Dieterich DT; Purow JM; Rajapaksa R
The hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) often co-infect the same individuals because they share comparable routes of transmission. Co-infection with HIV in those patients infected with HCV influences the accuracy of HCV diagnostic testing, levels of HCV viremia, severity of liver histopathology, and rate of progression to cirrhosis. By contrast, the effect of HCV co-infection on HIV disease is unclear. Nevertheless, the combination therapy containing recombinant interferon alfa-2b (rIFN-alpha 2b) plus ribavirin has been shown to be efficacious in the treatment of chronic hepatitis C, whereas alpha interferon monotherapy has been shown to be efficacious in patients co-infected with HCV and HIV. It is therefore logical to propose and test the hypothesis that combination rIFN-alpha 2b/ribavirin therapy will also benefit patients who are co-infected with HCV and HIV. A double-blind, placebo-controlled study is presently under way to investigate this hypothesis
PMID: 10349696
ISSN: 0272-8087
CID: 14720

Testosterone replacement therapy for HIV-related wasting: abstract and commentary [Comment]

Dieterich DT
PMID: 9851485
ISSN: 0098-7484
CID: 8026