About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods.Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: ( a ) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels ( Ͼ 1,000 HIV-1 copies/10 5 PBMC and Ͼ 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; ( b ) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; ( c ) a significantly lower ( Ͼ 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern.These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants. ( J. Clin. Invest. 1996. 97:323-330.)

Biomarkers have a wide application in research and clinic, they help to choose the correct treatment for diseases. Recent studies, addressing the vaginal microbiome using next generation sequencing (NGS), reported the involvement of bacterial species in infertility. We compared the vaginal microbiome of idiopathic infertile women with that of healthy, including bacterial vaginosis affected women and non-idiopathic infertile women, to identify bacterial species suitable as biomarkers. Information on microorganisms was obtained from the V3-16S rDNA sequencing of cervical-vaginal fluids of 96 women using the Ion Torrent platform. Data were processed with QIIME and classified against the Vaginal 16S rDNA Reference Database. The analysis revealed a significant beta-diversity variation (p < 0.001) between the four groups included in the study. L. iners, L. crispatus, and L. gasseri distinguished idiopathic infertile women from the other groups. In these women, a microbial profile similar to that observed in bacterial vaginosis women has been detected. Our results suggest that the quantitative assessment and identification of specific microorganisms of the cervical-vaginal microflora could increase the accuracy of available tools for the diagnosis of infertility and improve the adoption of therapeutic protocols.

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.

Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with the local immune mediators, providing an opportunity to define the link between vaginal commensal microorganisms and opportunistic pathogens in the relation of a given vaginal community state type (CST). A total of 90 vaginal samples from Caucasian asymptomatic women of reproductive age (18-40 years) attending the yearly examination and not reporting any vaginal complaints were retrospectively evaluated for microbiome assessment and immune factor dosage. The samples were tested by the Ion Torrent PGM and the Luminex Bio-Plex technologies for the analysis of microbiome and immune factors, respectively. In our study, the CST classification together with the local immune response profiling represented a good predictive indicator of the vaginal health, suggesting that the predominance of a specific Lactobacillus and its relative abundance are pivotal elements to maintain a physiologic status. A vaginal colonization from Bifidobacterium may absolve a protective role similar to that of Lactobacillus, corresponding to a newly identified CST, although studies are needed to better clarify its clinical significance. Moreover, within each CST, a different pattern of inflammation is activated and orchestrated both by the dominant Lactobacillus spp. and by specific non-Lactobacillus bacteria and can give insights into the pathogenic mechanisms. In conclusion, this study contributes to the characterization of vaginal dysbiosis, reshaping this concept by taking into consideration the CST profiling, local immune marker, and immune-microbial network.

To assess HCV genotype distribution and its determinants, 318 consecutive HCV RNA positive patients were examined. Subtype 1b infection was the most prevalent (35.5%), followed by subtype 1a (22%), 3a (21.4%) and 2 genotype (21.3%). Subtypes 1a, 1b and 3a had a comparable prevalence (30-35%) in the 0-15-, 16-30- and 31-45-year age groups. In subjects older than 45 years, genotype 2 prevalence increased, whereas subtype 1a and 3a infections decreased markedly. In this age group types 1b and 2 accounted for a prevalence of more than 90% in a comparable proportion. Genotype prevalence rates according to different risk factors were different statistically (P < 0.001): subtype 1a and 3a infections were predominant in injection drug users (42.9% and 37.7%, respectively), whereas community acquired infections and infections in patients with a history of transfusion were caused mainly by subtype 1b (38.5% and 66.6%, respectively). Logistic regression showed that age and injection drug use are independent determinants of genotype distribution.

HIV infection is characterized by the reduction of the CD4 ϩ , CD45RA ϩ , CD26 ϩ , and CD28 ϩ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-␥ ; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4 ϩ , CD45RA ϩ , CD45R0 ϩ , and CD26 ϩ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-␥ , RANTES, and sCD30 in HIV ϩ patients.10 HIV ϩ patients with CD4 cell counts between 200 and 500 cells/mm 3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4 ϩ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA ϩ /CD26 ϩ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-␥ , and sCD30 were significantly upregulated.These results demonstrate that rIL-2 in HIV ϩ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-␥ . These effects may be beneficial to HIV ϩ patients by improving their immune response to microorganisms or vaccines. ( J. Clin.

Chlamydia trachomatis causing chronic inflammatory diseases has investigated as possible human papillomavirus (HPV) cofactor in cervical cancer. The aim of this study is to evaluate the prevalence of Chlamydia trachomatis and HPV co-infection in different cohorts of asymptomatic women from a Northern Italy area at high incidence for cervical cancer. Cervical samples from 441 females were collected from Cervical Cancer Screening Program, Sexually Transmitted Infectious and Assisted Reproductive Technology centres. HPV and Chlamydia trachomatis were detected simultaneously and genotyped using a highly sensitive bead based assay. The overall prevalence of Chlamydia trachomatis was estimated 9.7%, in contrast with the reported national data of 2.3%, and co-infection with HPV was diagnosed in the 17% of the samples. In females ≤ 25 years of age, the infection reached a peak of 22% and co-infection with HPV of 45.8% (P < 0.001). Of note, in young females diagnosed with low grade cervical lesions, no significant difference between Chlamydia trachomatis and HPV distribution was observed, while differently, HPV co-infection was found significantly associated to the presence of intraepithelial lesions when compared to older females (20% vs. 1%; P < 0.001). In this study, the use of a high sensitive molecular technique exhibited higher analytical sensitivity than the referred assays for the diagnosis of Chlamydia trachomatis and HPV co-infection in asymptomatic females, leading to reduction of the potential to identify incorrectly the infection status. An active screening for timely treatment of Chlamydia trachomatis infection is suggested in young females to evaluate a possible decrease in incidence of pre-cancer intraepithelial lesions.

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