病毒学和免疫学随访经4-9年四种病毒抑制药包括整合酶抑制剂结合短程药物轮转AIDS治疗

• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: 逆转录病毒科 整合酶抑制剂 玫瑰树碱类 啶黄 维生素B12 HⅣ-1
• 年，卷（期）: 2002,（1）
• 所属期刊栏目: 研究原著
• 页码范围: 1-15
• 页数: 15页
• 分类号: R96
• 语种: 英文

摘要

AIM: To present the 4 to 9 years (median: 6 years)treatment follow up of 10 HIV1-AIDS patients, 9 at AIDS and 1 at A3 stages. METHODS: We have applied from 1992 to 1994, AZT combined with 2 integrase inhibitors,acriflavine and hydroxy-methyl-ellipticine. We could shift, in 1994, to combinations of 3 drugs including two more retrowanscfiptase inhibitors (RTI), ddI and ddC,and, after 1995, to combinations of 4 drugs including also two other RTI, d4T and 3TC, and 3 protease inhibitors (PI), indinavir, ritonavir, and saquinavir. In 1998, as cobalamine was shown by an in vitro test, to act as integrase inhibitor, vitamin B12 was added in cycles of various lengths. Every three weeks, not only the investigations were repeated, but the virostatics were changed. RESULTS: No grade 2 virostatics toxicity has been registered. The viral loads (VL) decreased according to exponential curves. Their initial parts obeyed first order kinetics. The second parts were and still are asymptotic. The first parts could be rectilinear or sinuous. The sinuosities were associated to cofactors present before treatment (chimerism, UV irradiation,hepatitis C or B and C, brain toxoplasmosis). The asymptotic parts, whose VL were below PCR detectable levels, presented discrete, reversible HIV1 rebounds,associated to other cofactors (such as herpes zoster,herpes 6, CMV, flat condyloma, and influenza).Among immunologic parameters, the monocyte and CTLnumbers increased and presented, during the rapidly decreasing part of VL curve, a significant inverse correlation with it. Neither CT4+ nor suppressor T-cell (STC) numbers presented such correlation. Near 100 %of CTL were CD28+ Later, vitamin B12 applications increased monocyte and CD28+ CTL numbers, and appeared to reinforce VL stabilization. CONCLU-SION: The combinations of inhibitors affecting 3retrovirus targets, retrotranscriptase, integrase, and protease have given to 10 out of 10 AIDS patients survivals varying today between 4 to 9 years, in excellent conditions. The UVA-pretreated patient is the only one presenting a not maximally reduced asymptotic VL, while his CD4 + and STC have been absent for 8 years. Other patient VL regressed exponentially to become asymptotic,below PCR detectable levels.