In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.
Zidovudine/lamivudine/tenofovir has good virological efficacy in advanced HIV disease. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often.
Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)-infected individuals and 12 transplant recipients. Nine normal volunteers acted as controls. The cells were washed and cytospins prepared. Monoclonal antibodies (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA-DR molecules as well as phenotypic macrophage markers. P values apply to the differences between medians using the Mann-Whitney test. Median percentages of macrophages, lymphocytes and neutrophils were similar in all three groups. No differences were found in the median percentages of macrophages expressing the monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and transplant recipients a median of only 45% of macrophages expressed the pan-macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the normal volunteers. The AM population expressing the dendritic cell marker (MoAb RFD1) was also markedly reduced in both groups of immunocompromised patients (2 vs 28% in normal volunteers). Transplant recipients had significantly more phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs 2%), but the numbers were still low when compared with the volunteers (48%). HLA-DR expression on BAL cells was reduced by 90% in both immunocompromised groups. For the transplant recipients, severity of pneumonitis was correlated with expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538, p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05), while no such correlation was found in HIV-infected patients. These results suggest that a defective macrophage population is probably a serious factor contributing to immunosuppression.
StMMARYMoAbs and itnmunopcroxidasc tiielhods were used to Identify antigen-presenting and phagocytic cells and lo assess expression of HLA-DR molecules on cells obtained by bronehoalveolar iavagc (BAD from 33 AIDS patients and nine normal volunteers. In I7patienls, not receiving antiretroviral Iherapy, lhe expression of HLA-DR tnoleeulcs (MoAb RFDRl) as well as the percentages oi'eells expressing RFDI marker for antigen-presenting cells and RFD7 marker for mature phagocytes were significantly rcdueed. However, in BAL obtained after commencing treatment with zidovudine (AZT)in2l patients or with 2'.3'-dideoxyinosinc(DDI)in five patients, the expression of the tnarkers studied was found to have returned to levels of expression seen in normal lavages. The changes observed were clearly associated with antirelroviral treatment and did tioteorrelale with applications ofother drugs, blood CD4 counts or presence of infectious organisms in BAL fluid. As lhe alterations in the expression of HLA-DR molecules and RFDI marker on macrophages have been shown lo be assoeialed wiih functional capacities of these cells, the reversal of impaired expression ofphenolypic markers on alveolar macrophages in A IDS patients by AZT and DDI signifies an important ability of these drugs to modify immune reactivity and emphasizes the need to monitor such functions in HIV disease. treatment reduces frequency of opportunistic infections [9.10], but il is not known whether antirelroviral treatment can alTeel functional capacities of maerophages. In order to establish lhe effect of such treatment, we studied the expression of cell markers, believed lo be associated wiih function on alveolar macrophages in three groups of HIV-infected patients presenting with pneumonitis; (i) individuals not receivinganliretroviral drugs, and (ii) patients treated with AZT, or (iii) with 2',3'-dideoxyinosine (DDI), Keywords MATERIALS AND METHODS Brtincliotilrciiltir linage and study popidaiionBronchoalveotar lavagc (BAL) of lhe appropriate lobe (as indicated by radiographic abnormality) or of the right middle lobe (in palients wiih normal radiographs or generalized radiographic shadowing) was carried out using a fibreopiie bronchoscopc. A subsegmcntal bronchus was anaesthetized using 2",. lignoeaine and lavaged with 20-ml aliquots of O9'M, saline (buffered to pH 7-4 with NaHCO,) to a loial of 180 ml. The lavage fluid was gently aspirated after each aliquot and collected into a sterile, siliconizcd glass bottle maintained at 4 C. 13
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