An immunohistochemical analysis with monoclonal antibody p16(INK4a) was performed in formalin-fixed, paraffin-embedded samples of 60 cases. The aim was to investigate in biopsies the expression of p16(INK4a) of normal uterine cervical tissue, pre-cancerous and cancerous lesions, and their relation with human papilloma virus (HPV) and HIV status. Three parameters were evaluated: percentage of p16(INK4a) positive cells, reaction intensity, and cell staining pattern. All of these parameters were statistically different when compared among different histological groups. However, logistic regression model showed that the reaction intensity was the best indicator of the expression of p16(INK4a). This expression increases from normal to invasive squamous carcinoma. Sixty-six percent of the patients with CIN grade 1 (CIN1) expressed p16(INK4a) (all these cases were infected with high risk HPV). Our study supports the hypothesis that p16(INK4a) expression in pre-cancerous lesions and cancers can be used to identify HPV-transformed cells. Of great interest for routine diagnostic use is the fact that immunohistochemical testing for p16(INK4a) seems to be capable of identifying HPV-positive cells and potentially recognizing those lesions with an increased risk of progression to high-grade lesions.
ResumoOBJETIVO: O objetivo foi descrever a distribuição dos genótipos do papilomavírus humano e a frequência de infecções por múltiplos genótipos, bem como avaliar a associação entre genótipos de papilomavírus humano, faixa etária e resultados cito-histopatológicos. MÉTODOS: Estudo retrospectivo de corte transversal realizado entre junho de 2010 e outubro de 2013 em Salvador, Bahia, Brasil. Foram revisados 351 prontuários de mulheres com genotipagem positiva pelo teste PapilloCheck ® , usado para detectar 24 tipos de papilomavírus humano. Os achados cito-histopatológicos foram classificados em grupos de: achados negativos para neoplasia (exames citopatológico e histopatológico negativos), lesão de baixo grau (achado citopatológico -lesão intraepitelial de baixo grau -ou achado histopatológico -neoplasia intraepitelial cervical grau 1, neoplasia intraepitelial vaginal grau 1 ou condiloma e lesão de alto grau (achado citopatológico -lesão intraepitelial de alto grau -ou histopatologia com laudo maior ou igual a neoplasia intraepitelial cervical grau 2 ou neoplasia intraepitelial vaginal grau 2). RESULTADOS: O genótipo de alto risco mais frequente foi o HPV 16, com 18,5%; intervalo de confiança de 95% (IC95%) 14,6-23,0, seguido pelo HPV 56 (14%; IC95% 10,5-18,0) e o HPV 39 (13,4%; IC95% 9,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)8). O HPV 18 (5,4%; IC95% 3,3-8,3) esteve entre os menos comuns. Entre os tipos de baixo grau, o HPV 42 (15,7%; IC 95% 12,0-20,0), o HPV 6 (11,4%; IC95% 8,3-15,2) e o HPV 44/55 (11,1%; IC95% 8,0-14,9) foram os mais encontrados, enquanto o HPV 11 (2,8%; IC95% 1,4-5,2) foi o menos frequente. A proporção do HPV 16 aumentou com a severidade das anormalidades cito-histopatológicas de 13,8% (12/87) nas lesões de baixo grau para 42,4% (14/33) nas lesões de alto grau. Houve associação significativa entre a presença de lesão cito-histopatológica de baixo ou alto grau e os genótipos de alto risco, HPV 16, HPV 52, HPV 73 e HPV 82, e o de baixo risco, HPV 43. Mulheres com menos de 30 anos apresentaram frequência significativamente maior do HPV 16 (22,2 versus 12,9%, p=0,01), do HPV 42 (19,7 versus 10,9%, p=0,01) e do HPV 45 (6,6 versus 1,4%, p=0,01), além de infecção múltipla (58,1 versus 47,4%, p=0,04). CONCLUSÕES: Observou-se uma variabilidade da distribuição dos diversos genótipos de papilomavírus humano em mulheres no estado da Bahia. Na amostra estudada, o HPV 16 foi o mais frequente, assim como em outras regiões do Brasil e do mundo. Encontramos o HPV 56 e o HPV 39 como o segundo e o terceiro mais frequentes. Entretanto, o HPV 18 esteve entre os menos comuns. Os tipos não oncogênicos, HPV 42, 6 e 44/55, foram os mais observados, enquanto o HPV11 foi o menos frequente.Abstract PURPOSE: The aim of this study was to evaluate the human papillomavirus genotypes and the frequency of multiple human papillomavirus infections, as well as to assess the association between human papillomavirus genotype, cyto-histopathological abnormalities and age range. METHODS: A retrospective cross-sectional study was ...
The risk of HIV-1 mother-to-child transmission (MTCT) is clearly correlated with the maternal HIV cell-free viral load (VL) at delivery. Preventing MTCT in late-presenting (after 28 weeks) HIV-infected pregnant women remains a clinical challenge, and ensuring a rapid decrease of maternal VL is an important preventive strategy. Raltegravir (RGV) has a higher first and second phase viral decay rate, has a high placental transfer, with a potential preloading effect for neonate, and demonstrates effective accumulation in cervicovaginal secretions. We report 14 cases in which RGV was used late in pregnancy for HIV-1 MTCT prophylaxis. All women were RGV naive and the prophylaxis regimens included RGV plus at least two other antiretroviral agents. At RGV initiation, the median gestational age was 36 weeks (range 34-38) and the median maternal plasma HIV-1 RNA viral load was 35,364 copies/ml (range 636-391,535). At delivery, the median gestational age was 38 weeks (range 37-40). The median exposure time to RGV was 17 days (range 7-32), with a mean maternal VL decay of 2.6 log. At delivery, seven women had undetectable ( < 50 copies/ml) VL, four had between 64 and 457 copies/ml, and in three VL was not available. All but one infant's HIV-RNA tests were negative at 1 and 3 months (one case of in utero MTCT). Raltegravir-containing antiretroviral regimens induced a rapid HIV-RNA decline in maternal VL at delivery, and were safe and effective in preventing MTCT for late-presenting, HIV-infected women.
The control of STI represents a unique opportunity to improve reproductive health of women living with HIV. STI diagnosis can change their behavior and reduce the sexual transmission of HIV and bacterial STI.
This study aimed to evaluate the prevalence of sexually transmitted infections (STIs) and associated risk factors in HIV-infected pregnant women followed for prenatal care in Salvador, Bahia. This was a cross-sectional study of 63 women seeking prenatal care at a reference center. Participants were interviewed regarding socio-epidemiological and clinical history, and were tested for HBsAg, anti-HCV, anti HTLV I/II, VDRL, Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis, Ureaplasma urealyticum, CD4 count, and HIV plasma viral load. The main outcome variable was the presence of any STI. The mean age of patients was 28.2 years (16-40 years). 23 (36.5%) were diagnosed with at least one STI. The frequency of diagnoses was: HBV, 3.2%; HCV, 8.1%; HTLV I/II, 3.4%; syphilis, 9.5%; Chlamydia trachomatis, 11.1%; HPV, 15.0%; Mycoplasma hominis, 2.1%, and Ureaplasma urealyticum, 2.1%. No case of Neisseria gonorrhoeae was identified. No association was found between socio-epidemiological variables and the presence of an STI. CD4 T lymphocyte < 500 cells/μL (p=0.047) and plasma viral load >1,000 copies (p = 0.027) were associated with the presence of STI. STIs are frequent in pregnant women infected with HIV, and all HIV-infected pregnant women should be screened to decrease transmission of these pathogens and to protect their own health.
Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA <50 copies per mL), in all patients who received at least one dose of study drugs (modified intention-to-treat analysis). Missing information was treated as failure. We assessed safety in all patients. Results We enrolled and randomly assigned treatment to 33 patients (17 in raltegravir group) between June 2015 and June 2017. The study was interrupted by the IRB because a significant difference between arms was detected in an interim analysis. All patients completed follow up at delivery. At delivery, virological suppression was achieved by 13/17 (76.5%) of patients in raltegravir group, versus 4/16 (25.0%) in lopinavir/ritonavir group (RR 3.1, 95% CI: 1.3-7.4). Patients in raltegravir group had significantly higher proportion of virological suppression at 2, 4, and 6 weeks than lopinavir/ritonavir group. Adverse events were most of mild intensity, but patients in lopinavir/ritonavir group had significantly more gastrointestinal adverse events. There was neither discontinuation nor deaths in this trial. Conclusion Raltegravir might be a first-line option for treatment of HIV-infected late-presenting pregnant women.
Human Papilloma Virus (HPV) plays a central role in the development of cervical cancer. However, other coexisting factors, such as HIV infection, must be present for this to occur. We evaluated the prevalence of HPV in HIV-positive and HIV-negative patients in the city of Salvador , Bahia, Brazil, and determined the most prevalent types of HPV in these patients. Fifty-five cases were selected from among patients attending three institutions providing cervical pathology services in the city of Salvador. HIV testing (Elisa/WB), HPV-DNA testing by PCR, colposcopy, cytology and biopsy were carried out in all patients. The histopathological results were classified as follows: 11 cases were normal/negative for neoplasia, 15 were diagnosed as cervical intraepithelial neoplasia grade 1 (CIN 1), 10 were CIN 2, 15 cases were CIN 3 and there were four cases of invasive squamous cell carcinoma. Among the 55 patients studied, 43 tested positive for HPV-DNA and 20 for HIV. All HIV-positive patients were positive for HPV-DNA. The most prevalent types of HPV were HPV 16, 52, 58, 53, 54, 33 and 51, and there was little difference between the groups of HIV-positive and HIV-negative patients with respect to the type of HPV encountered. The HIV-positive patients were found to be infected with a greater number of types of HPV than the HIV-negative patients. This study corroborates the existence of regional variations in the distribution of certain types of HPV, which is probably due to the particular ethnic constitution found in this region of Brazil. Key Words: Human papilloma virus (HPV), human immunodeficiency virus (HIV), cervical intraepithelial neoplasias (CIN), cervical invasive carcinoma.Invasive squamous cell cervical cancer develops from well-defined precancerous lesions, which can potentially progress to invasive disease if they are not detected early and treated. There is epidemiological and molecular evidence that infection by human papilloma virus (HPV) plays an important role in the development of uterine cancer [1]. However, infection by oncogenic HPV types is necessary but insufficient to cause cervical cancer [2], the association of other coexisting factors in addition to HPV is necessary to modulate the transition from cervical infection to cancer.Some coexisting factors inherent to HPV influence the risk of progression of CINs and the development of cervical cancer. This risk is related to the HPV genotype, variants, viral load, persistence, and integration of the viral DNA of the host genome [1,[3][4][5][6]. Currently accepted coexisting factors related to the host are high parity, prolonged use of oral contraceptives [7][8][9][10][11], smoking [12,13], and sexually transmitted diseases (STD), such as herpes simplex virus type 2, Chlamydia trachomatis [14,15] and, especially, acquired immunodeficiency syndrome (AIDS), [16,17].The first report relating cervical intraepithelial neoplasia (CIN) to HIV was published by Bradbier [18]. Other publications followed and, based on this information, invasive squamous cell ...
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