Current recommendations state that antiretroviral therapy (ART) should be commenced before the onset of severe HIV-associated immune deficiency and the development of AIDS-defining infections or malignancies. However, many patients only present and are diagnosed with HIV infection when they already have advanced disease. The optimal treatment for patients with advanced HIV disease remains to be defined. Key management questions include whether the virological and immunological responses to ART are comparable to those seen in patients with less advanced disease; whether the efficacy of different antiretroviral (ARV) regimens differs in patients with advanced disease; and whether there is an increased risk of drug toxicity and the immune reconstitution inflammatory syndrome.
Girardi E, Sampaolesi A, Gentile M, et al.Increasing proportion of late diagnosis of HIV infection among patients with AIDS in Italy following introduction of combination antiretroviral therapy. J Acquir Immune Defic Syndr2000;25(1):71-76.
2.
Castilla J, Sobrino P, De La Fuente L, et al.Late diagnosis of HIV infection in the era of highly active antiretroviral therapy: Consequences for AIDS incidence. AIDS2002;16(14):1945-1951.
3.
Sabin CA, Lampe FC, Chaloner C, et al.An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: The limitations of observational databases when auditing antiretroviral treatment use. HIV Med2003;4(2):87-93.
4.
Health Protection Agency, SCIEH, ISD, National Public Health Service for Wales, CDSC Northern Ireland and the UASSG. Renewing the focus. HIV and other sexually transmitted infections in the United Kingdom in 2002. An update: November 2003. Accessed November 4, 2004, from http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/publications/annual2003/annual2003.pdf
5.
McDonald AM, Li Y, Dore GJet al.Late HIV presentation among AIDS cases in Australia, 1992-2001. Aust N Z J Public Health2003;27(6):608-613.
6.
Neal JJ, Fleming PL. Frequency and predictors of late HIV diagnosis in the United States, 1994 through 1999. 9th Conference on Retroviruses and Opportunistic Infections. February24-28, 2002. Seattle. [Abstract 474-M]
7.
Burns FM, Fakoya AO, Copas AJ, French PD. Africans in London continue to present with advanced HIV disease in the era of highly active antiretroviral therapy. AIDS2001;15(18):2453-2455.
8.
Late versus early testing of HIV - 16 sites, United States, 2000-2003. MMWR Morb Mortal Wkly Rep2003;52(25):581-586.
9.
Panel on Clinical Practices for Treatment of HIV Infection, US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2004.
10.
Yeni PG, Hammer SM, Hirsch MS, et al.Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA2004;292(2):251-265.
11.
Pozniak A, Gazzard B, Anderson J, et al.British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med2003;4 (Suppl 1):1-41.
12.
Egger M, May M, Chene G, et al.Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies. Lancet2002;360(9327):119-129.
13.
Chene G, Sterne JA, May M, et al.Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: Analysis of prospective studies. Lancet2003;362:679-686.
14.
Hogg RS, Yip B, Chan KJ, et al.Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA2001;286(20):2568-2577.
15.
Ahdieh-Grant L, Yamashita TE, Phair JP, et al.When to initiate highly active antiretroviral therapy: A cohort approach. Am J Epidemiol2003;157(8):738-746.
16.
Staszewski S, Morales-Ramirez J, Tashima KT, et al.Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med1999;341(25):1865-1873.
17.
Albrecht MA, Bosch RJ, Hammer SM, et al.Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N Engl J Med2001;345(6):398-407.
18.
Lucas GM, Chaisson RE, Moore RD. Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz. AIDS2001;15(13):1679-1686.
19.
Bartlett JA, Johnson J, Herrera G, et al.Initial therapy with abacavir + lamivudine (ABC+3TC) combined with efavirenz (NNRTI), amprenavir/ritonavir (PI) or stavudine (NRTI): ESS40001(CLASS). XIV International AIDS Conference. July 7 - 12, 2002. Barcelona, Spain. [Abstract TuPeB4544]
20.
Squires K, Lazzarin A, Gatell JM, et al.Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr2004;36(5):1011-1019.
21.
Hicks C, King MS, Gulick RM, et al.Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study. AIDS2004;18(5):775-779.
22.
Miro JM, Antela A, Arrizabalaga J, et al.[Recommendation of GESIDA (AIDS Study Group)/National Plan on AIDS with respect to the anti-retroviral treatment in adult patients infected with the human immunodeficiency virus in the year 2000 (I)]. Enferm Infecc Microbiol Clin2000;18(7):329-351.
23.
Floridia M, Fragola V, Galluzzo CM, et al.HIV-related morbidity and mortality in patients starting protease inhibitors in very advanced HIV disease (CD4 count of < 50 cells/microL): An analysis of 338 clinical events from a randomized clinical trial. HIV Med2002;3(2):75-84.
24.
Gathe JC Jr., Ive P, Wood R, et al.SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS2004;18(11):1529-1537.
25.
van Leth F, Phanuphak P, Ruxrungtham K, et al.Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: A randomised open-label trial, the 2NN Study. Lancet2004;363(9417):1253-1263.
26.
van Leth F, Andrews S, Grinsztjen B, et al.Virologic failure in antiretroviral therapy naive patients is only determined by extreme low values of CD4+ cells or high values of HIV-1 RNA concentration, not by choice of treatment with nevirapine or efavirenz. 11th Conference on Retroviruses and Opportunistic Infections. February 8 -11, 2004. San Francisco. [Abstract 550]
27.
Phillips AN, Staszewski S, Weber R, et al.HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA2001;286(20):2560-2567.
28.
Fischl MA, Ribaudo HJ, Collier AC, et al.A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease. J Infect Dis2003;188(5):625-634.
29.
Rodriguez-French A, Boghossian J, Gray GE, et al.The NEAT study: A 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. J Acquir Immune Defic Syndr2004; 35(1):22-32.
30.
Ruane P, Mendonca J, Timerman A, et al.Kaletra vs. nelfinavir in antiretroviral-naive subjects: Week 60 comparison in a phase III, blinded, randomized clinical trial. 1st International AIDS Society Conference on HIV Pathogenesis and Treatment. July 8 - 11, 2001. Buenos Aires, Argentina. [Abstract 6]
31.
Gulick RM, Ribaudo HJ, Shikuma CM, et al.Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med2004;350(18):1850-1861.
32.
Waters L, Stebbing J, Jones R, et al.A comparison of the CD4 response to antiretroviral regimens in patients commencing therapy with low CD4 counts. J Antimicrob Chemother2004;54(2):503-507.
33.
The EfaVIP Cohort Study Group. Clinical, virologic, and immunologic response to efavirenz- or protease inhibitor-based highly active antiretroviral therapy in a cohort of antiretroviral-naive patients with advanced HIV infection (EfaVIP 2 Study). J Acquir Immune Defic Syndr2004;35(4):343-350.
34.
Friedl AC, Ledergerber B, Flepp M, et al.Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy. The Swiss HIV Cohort Study. AIDS2001;15(14):1793-1800.
35.
Arribas JR, Pulido F, Miro JM, et al.High effectiveness of efavirenz-based highly active antiretroviral therapy in HIV-1-infected patients with fewer than 100 CD4 cells/microl and opportunistic diseases: The EfaVIP Study (Efavirenz in Very Immunosuppressed Patients). AIDS2002;16(11):1554-1556.
36.
Easterbrook P, Wilkins E, Gazzard B, et al.Efficacy and tolerability of trizivir plus efavirenz in antiretroviral naive adults with advanced HIV disease at 48 weeks: The Tetra study. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. September 14 - 17, 2003. Chicago. [Abstract 4745]
37.
Williams I, Asboe D, Babiker A, Goodall R, Hooker M. A virological benefit from an induction/maintenance strategy compared with a standard 3-drug regimen in anti-retroviral naive patients: The FORTE trial. 11th Conference on Retroviruses and Opportunistic Infections. February 8 -11, 2004. San Francisco. [Abstract 564]
38.
Shafer RW, Smeaton LM, Robbins GK, et al.Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med2003;349(24): 2304-2315.
39.
Katlama C, Carcelain G, Duvivier C, et al.Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: The ILSTIM study-ANRS 082. AIDS2002;16(15):2027-2034.
40.
Marchetti G, Meroni L, Varchetta S, et al.Low-dose prolonged intermittent interleukin-2 adjuvant therapy: Results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment. J Infect Dis2002;186(5):606-616.
41.
David D, Nait-Ighil L, Dupont B, Maral J, Gachot B, Theze J. Rapid effect of interleukin-2 therapy in human immunodeficiency virus-infected patients whose CD4 cell counts increase only slightly in response to combined antiretroviral treatment. J Infect Dis2001; 183(5):730-735.
42.
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 Med1999;130(7):570-577.
43.
Michelet C, Arvieux C, Francois C, et al.Opportunistic infections occurring during highly active antiretroviral treatment. AIDS1998;12(14):1815-1822.
44.
Brechtl JR, Breitbart W, Galietta M, Krivo S, Rosenfeld B. The use of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: Impact on medical, palliative care, and quality of life outcomes. J Pain Symptom Manage2001;21(1):41-51.
45.
French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS2004;18(12):1615-1627.
46.
French MA, Lenzo N, John M, et al.Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med2000;1(2):107-115.
47.
Hirsch HH, Kaufmann G, Sendi P, Battegay M. Immune reconstitution in HIV-infected patients. Clin Infect Dis2004;38(8):1159-1166.
