Management of HIV Infection
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HIV disease is a serious global health problem and a major cause of morbidity and mortality worldwide. It has recently been estimated that more than 30 million adults and 1.1 million children are infected with HIV; it is expected that 40 million people will have acquired the virus by the year 2000. The high costs of treating patients with HIV infection place a heavy burden on healthcare resources.
Primary aims of management of patients with HIV infection are decreased morbidity and improved survival via sustained suppression of HIV replication and the prevention of emergence of drug-resistant virus. Triple therapy with combinations of antiretroviral drugs is now regarded as optimal treatment and is the standard of care in most developed countries. Two nucleoside analogue reverse transcriptase inhibitors, such as lamivudine and zidovudine, plus a protease inhibitor or a non-nucleoside analogue reverse transcriptase inhibitor are among the combinations of drugs recommended for initial or second-line treatment.
A combination formulation of lamivudine and zidovudine has recently become available; it can be taken as a single tablet twice daily rather than as 8 tablets per day when the 2 drugs are given separately.
Combination therapy with lamivudine and zidovudine (as dual therapy or in combination with another nucleoside analogue reverse transcriptase inhibitor) decreases the rate of HIV disease progression in antiretroviral therapy-naive or -experienced patients. Dual therapy with lamivudine and zidovudine or triple therapy with lamivudine and zidovudine-containing regimens produces reductions in HIV RNA levels and improvements in CD4+ cell counts.
Lamivudine plus zidovudine therapy, alone or in combination with other drugs, is generally well tolerated. Gastrointestinal symptoms are the most common events reported during dual therapy with the 2 drugs. Neutropenia and anaemia may also occur during combination therapy with lamivudine and zidovudine and blood counts must be monitored regularly for signs of haematological toxicity.
Thus, the combination formulation of lamivudine and zidovudine has a potentially useful role as a component of initial or second-line treatment regimens for patients with HIV infection. Reducing the number of tablets that have to be taken each day simplifies the administration of lamivudine and zidovudine. The combination formulation is likely to be particularly beneficial in the management of patients who find it difficult to adhere to more complex treatment regimens.
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- 1.GlaxoWellcome USA. Lamivudine/zidovudine prescribing information. 1998Google Scholar
- 7.Anon. The pathogenesis of AIDS. Sci Med 1997 Mar–Apr; 4: 6–13Google Scholar
- 8.Anon. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep 1992 Dec 18; 41(RR-17): 1–18Google Scholar
- 15.Anon. Recent statistics on the global burden of HIV infection/AIDS. Pharmacoecon Outcomes News 1997; 141: 11Google Scholar
- 21.Chen HX, Ryan PA, Ferguson RP, et al. Characteristics of acquired immunodeficiency syndrome in older adults. J Am Geriate Soc 1998 Feb; 46: 153–6Google Scholar
- 30.Update: trends in AIDS incidence–United States, 1996. MMWR Morb Mortal Wkly Rep 1997 Sep 19; 46: 861-7Google Scholar
- 33.Johnson VA. New developments in antiretroviral drug therapy for HIV-1 infections. AIDS Clin Rev 1995-96: 305-46Google Scholar
- 37.Greener M. Recent advances in the treatment of HIV disease. AIDS Lett 1998 (65): 1–3Google Scholar
- 45.Daly P, Green SL, Freimuth WW, et al. An open-label randomized study of Rescriptor (DLV, delavirdine mesylate) in triple and quadruple combinations with zidovudine (ZDV), in-dinavir (IDV) and lamivudine (3TC) in HTV-1 infected individuals [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 84Google Scholar
- 46.Staszewski S, Morales-Ramirez J, Flanigan T, et al. A phase II, multicenter, randomized, open-label study to compare the antiretroviral activity and tolerability of efavirenz (EFV) + indinavir (IDV), versus EFV + zidovudine (ZDV) + lamivudine (3TC) versus IDV + ZDV + 3TC at 24 weeks [DMP 266-006] [abstract] [Poster]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 330Google Scholar
- 47.Haas D, Seekins D, Cooper R, et al. A phase II, double-blind, placebo-controlled, dose ranging study to assess the antiretroviral activity and safety of efavirenz (EFV Sustiva, DMP 266) in combination with open-label zidovudine with lamivudine at 36 weeks [DMP 266-005] [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 330Google Scholar
- 48.Morales-Ramirez J, Tashima K, Hardy D, et al. A phase II, multicenter, randomized. open label study to compare the antiretroviral activity and tolerability of Efavirenz (EFV) + Indinavir (IDV), versus EFV + zidovudine (ZDV)+lamivudine (3TC), versus IDV + 3TC AT >36 weeks PMP 266-006] [abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. 1998 Sep 24–27; San Diego, 394Google Scholar
- 49.Anon. Guidelines for the use of antiretroviral agents in pediatric HIV infection. MMWR Morb Mortal Wkly Rep 1998; 47(RR-4): 1–31Google Scholar
- 54.Harrigan PR, Kinghorn I, Kohli A, et al. Virological response to AZT/3TC combination therapy in AZT-naive patients (Trial NUCB 3001) [abstract]. J Acquir Immune Defic Syndrom Hum Retrovirol 1995; 10 Suppl. 3: S27–8Google Scholar
- 56.Data on file. 1998 (GlaxoWellcome Inc. North Carolina, USA)Google Scholar
- 57.Moore KHP, Lloyd PP, Duncan B, et al. Bioequivalence of Combivir tablets and Epivir plus Retrovir tablets [abstract]. 5th Conference on Retroviruses and Opportunistic Infections. 1998 Feb 1–5; Chicago, 205Google Scholar
- 61.Rozenbaum W, Chauveau E. Phase 3 study of the antiviral activity of AZT+3TC given as separate regimens versus a new fixed dose combination (COMBIVIR) [abstract]. 5th Conference on Retroviruses and Opportunistic Infections. 1998 Feb 1–5; Chicago Google Scholar
- 62.Yetzer E, Eron J, Shaefer M, et al. Combivir (Lamivudine (3TC) 150mg/Zidovudine (ZDV) 300mg) given BID + a protease inhibitor (PI) compared with 3TC 150 mg BID and ZDV 200 mg TID + a PI [abstract]. 38th Interscience Conference on Antimicrob Agents Chemother. 1998 Sep 24–27; San Diego, 440Google Scholar
- 63.Shaefer M, Eron J, Yetzer E, et al. Combivir (lamivudine (3TC) 150 mg/zidovudine (ZDV) 300 mg) given BID plus a protease inhibitor (PI) compared to 3TC 150mg BID and ZDV 200mg TID plus a PI [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 55Google Scholar
- 64.Henry K, Shaeffer MS, Bellman P, et al. Preliminary data of effective switch/intensification treatment with Combivir and Ziagen in therapy-experienced patients. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. 1998 Sep 24–27; San Diego, 392Google Scholar
- 66.van Leeuwen R, Lange JMA, Nijhuis M, et al. Results of long-term follow-up of HIV-infected patients treated with lamivudine monotherapy, followed by a combination of lamivudine and zidovudine. Antiviral Ther 1997 Apr; 2: 79–90Google Scholar
- 71.Lafeuillade A, Poggi C, Djediouane A, et al. A pilot study of a combination of three reverse transcriptase inhibitors in HIV-1 infection. Antiviral Ther 1997 Dec; 2: 219–27Google Scholar
- 72.Gallant J, Seekins D, Hicks C, et al. A phase II, double-blind, placebo-control, dose-ranging study to assess the antiretroviral activity and safety of Efavirenz (EFV, SUSTIVA, DMP266) in combination with open-label zidovudine (ZDV) w/lamivudine (3TC) at >48 weeks.[DMP266-005]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. Sep 24–27; San Diego, 441Google Scholar
- 73.Boucher CAB, Borleffs J, et al. Long-term evaluation of saquinavir-soft-gel-capsule or indinavir as part of combination triple therapy (CHEESE study) [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 65Google Scholar
- 74.Borleffs JC, Boucher CA, Bravenboer B, et al. Saquinavir-soft gelatine capsules versus indinavir as part of AZT and 3TC containing triple therapy [abstract]. 37th ICAAC 1997 Sep 28: 260Google Scholar
- 75.Eron J, Peterson D, Murphy R, et al. An open-label, randomized, comparative study of d4T + ddI + IDV versus ZDV + 3TC + IDV in treatment naive HIV-infected patients (START II) [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 812Google Scholar
- 76.Mayers D, Jemsak J, Eyster E, et al. A double-blind, placebocontrolled study to assess the safety, tolerability and antiretroviral activity of efavirenz (EFV, Sustiva DMP 266) in combination with open-label zidovudine (ZDV) and lamivudine (3TC) in HIV-1 infected patients [DMP 266-004] [abstract]. 12th World AIDS Conference. 1998 Jun 28–Jul 3; Geneva, 331Google Scholar
- 78.Eron J, Yetzer E, Poertz D, et al. Combivir, a fixed formulation of lamivudine (3TC) 150 mg and zidovudine (ZDV) 300 mg given BID plus a protease inhibitor (PI) compared to 3TC 150 mg BID and ZDV 200 mg TID plus a PI [abstract]. 5th Conference on Retroviruses and Opportunistic Infections. 1998 Feb 1–5, Chicago, 151Google Scholar
- 79.Hirsch M, Meibohm A, Rawlins S, et al. Indinavir (IDV) in combination with zidovudine (ZDV) and lamivudine (3TC) in ZDV-experienced patients with CD4+ cell counts <50 cells/mm3 [abstract]. 4th Conference on Retroviruses and Opportunistic Infections 1997 Jan 22–26; Washington, DC 1997Google Scholar
- 81.Elwood E. Efavirenz offers new options in HIV infection. In-pharma 1998; 1(1148): 5–6Google Scholar
- 82.Hill A, Gazzard B, AVANTI Steering Committee, et al. Low frequency of genotypic mutations associated with resistance to AZT and 3TC after combination treatment with indinavir [abstract]. 12th World Conference. 1998 Jun 28–Jul 3; Geneva, 812Google Scholar
- 85.US audit of HIV drug use in 1997. Pharmacoecon Outcomes News 1998 Feb 7; 148: 11Google Scholar
- 86.Todd C. Lamivudine spares resources in HIV infection, reveals CAESAR study. Pharmacoecon Outcomes News 1998; 27(168): 3–4Google Scholar