Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/μL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, β-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.

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Human papillomavirus type 16 (HPV-16) transcription was analysed in one squamous cervical carcinoma by cDNA cloning and DNA sequencing, and in eight additional squamous cervical carcinomas and 11 precancerous lesions by RNA-RNA in situ hybridization. The nucleotide sequences of the cDNA clones revealed structures of early HPV-16 mRNAs (E6*-^ E7-E1 E4-E5) in agreement with data reported for other premalignant and malignant tumours, cDNA clones possibly representing viral RNA of antisense orientation were also detected. These RNAs included sequences of the upstream regulatory region, part of the early and the late region of the genome. In three of eight squamous cervical carcinomas examined by in situ hybridization, signals specific for viral antisense RNA were also found. The antisense RNAs had a predominantly nuclear localization. Viral antisense RNA could not be detected in any of 11 HPV-16-positive premalignant lesions. The expression of HPV antisense RNA is likely to be linked to viral integration into the host genome. The possible effects of viral antisense transcription with regard to tumour progression remain to be determined.

Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/μL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, β-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.

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We studied the prognostic value on the decrease of CD4 lymphocyte count of anti-p24 antibody (ab) titer and compared this value with that of polyclonal and monoclonal p24 (ag) titer before and after immune complex dissociation (ICD); 53 human immunodeficiency virus (HIV)-infected patients having CD4+ counts above 400/mm3 when first examined were followed up over a 3-year period including at least four visits; HIV disease progressors (n = 18) were defined as having CD4+ counts below 200/mm3 and non-progressors (n = 35) as having CD4+ counts still above 400/mm3 at the end of follow-up. Sera were collected at each visit and assayed for p24 ag with and without ICD and for anti-p24 ab titer. The mean anti-p24 ab titer of progressors and of non-progressors at entry was significantly different. A threshold of anti-p24 ab titer indicating a HIV progression was determined at 1/300. The proportion of individuals with an anti-p24 ab titer lower than 1/300 at least once during the study period was 34% in non-progressors and 94% in progressors. The difference between progressors and non-progressors at entry was significant with monoclonal p24 ag without ICD and more significant with monoclonal p24 ag after ICD. The marker having the highest predictive value was the anti-p24 ab titer, then monoclonal p24 ag with ICD, then polyclonal p24 ag with ICD. Anti-p24 ab is an earlier and stronger marker of the decrease of CD4 lymphocyte count than p24 ag even after ICD.