The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism.

Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder. During the last 15 years, advances in genomic technologies and the availability of increasingly large patient cohorts have greatly expanded our knowledge of the genetic architecture of ASD and its neurobiological mechanisms. Over two hundred risk regions and genes carrying rare de novo and transmitted high-impact variants have been identified. Additionally, common variants with small individual effect size are also important, and a number of loci are now being uncovered. At the same time, these new insights have highlighted ongoing challenges. In this perspective article, we summarize developments in ASD genetic research and address the enormous impact of large-scale genomic initiatives on ASD gene discovery.

Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women.

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.

Predictors of HPV incidence and clearance in a cohort of Brazilian HIV-infected women.

Persistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents a higher rate of persistent infections and an earlier progression to cancer. We aimed to evaluate HR-HPV prevalence, incidence and clearance, and its association with HIV viral suppression, immunological response and other risk factors among WLHA followed at an STD/HIV reference center. This was a cohort study conducted at a reference center for STD/AIDS in Northeastern Brazil from September 2013 to September 2015. Follow-up visits were conducted at 6 and 12 months after enrolment, where socio-epidemiological data were obtained. Cervical samples were collected for conventional cytology and HPV DNA research (PCR COBAS® Roche) in addition to blood samples for CD4+ T lymphocyte count and HIV viral load. We prospectively evaluated 333 women. HR-HPV DNA prevalence was 33.3% at baseline. HPV-16 was present in 5.1%, HPV-18 in 3.9% and 29.4% WLHA had other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The HR-HPV incidence during the follow-up was 10.8%, at the 6-month visit was 7.7% and at the 12-month visit was 3.7%. Variables associated with HR-HPV incidence were: nulliparity, combined oral contraceptive use and detectable HIV viral load. The HR-HPV clearance rate was 41.7% and was associated with age >30 years and lymphocyte T CD4 count >500 cells/mm3 at enrolment. These findings contribute to the knowledge about a group of women that need more careful HPV screening and describe the association between an efficient immunological response and HIV viral suppression with lower incidence and increased clearance of HR-HPV.

Anogenital infection by Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected men and women in Salvador, Brazil.

BACKGROUND: Infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae are the most common bacterial sexually transmitted infections throughout the world. These sexually transmitted infections are a growing problem in people living with HIV/AIDS. However, the presence of these agents in extra genital sites, remains poorly studied in our country. The objective of this study was to estimate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae anal and genital infection in people living with HIV/AIDS followed in a reference center in Salvador, Brazil. METHODS: Cross-sectional study, from June 2013 to June 2015. Proven HIV-infected people attending this reference center were invited. Clinical and epidemiological data were obtained through interview with standardized form. Chlamydia trachomatis and Neisseria gonorrhoeae screening was performed using qPCR (COBAS 4800® Roche). RESULTS: The frequency of positive cases of Chlamydia trachomatis and Neisseria gonorrhoeae was 12.3% in total, 9.2% cases amongst women and 17.1% amongst men. We found 14.0% of positive cases in anus and 3.1% in genital region in men, while 5.6% and 3.6%, in women, respectively. Among men, anal infection was associated with age <29 years (p=0.033), report of anal intercourse (p=0.029), pain during anal intercourse (p=0.028). On the other hand, no association between genital infection and other variables were detected in bivariate analysis. Among women, we detected an association between Chlamydia trachomatis genital infection and age <29 years (p<0.001), younger age at first sexual intercourse (p=0.048), pregnancy (p<0.001), viral load >50copies/mL (p=0.020), and no antiretroviral use (p=0.008). Anal infection in women was associated with age <29 years old (p<0.001) and pregnancy (p=0.023), and was not associated with report of anal intercourse (p=0.485). CONCLUSION: Missed opportunities for diagnosis in extra genital sites could impact on HIV transmission. The extra genital sites need to be considered to break the HIV and bacterial sexually transmitted infections chain-of-transmission.

Use of new antiretroviral drugs and classes in Bahia, Brazil: a real life experience on salvage therapy of AIDS patients.

Antiretroviral therapy has significantly evolved in the last decade, with an increasing number of new drugs and classes. Currently, even heavily experienced patients can be successfully treated with new regimens. In Brazil, the recent incorporation of some new antiretroviral drugs made it possible to suppress HIV plasma viremia in most treated patients, with significant benefits in terms of quality of life and survival. However, little has been published on outcomes of patients under new drugs-based regimens. We reviewed the safety and efficacy of antiretroviral regimens using recently introduced drugs in Bahia. Our results confirm that patients using darunavir, raltegravir, enfuvirtide, or etravirine presented with a high rate of virological suppression without significant adverse events, after one year of follow-up.

Syphilis and HIV-1 among parturient women in Salvador, Brazil: low prevalence of syphilis and high rate of loss to follow-up in HIV-infected women.

BACKGROUND: The occurrence of syphilis and HIV-1 infections during pregnancy are major risks to the fetus due to mother-to-child transmission (MTCT). OBJECTIVES: To determine peripartum seroprevalence and risk factors of syphilis and HIV-1 infection among pregnant women in Salvador, Brazil, and the rate of HIV-1 MTCT. METHODS: Cross-sectional study of pregnant women who were admitted for delivery in a reference maternity hospital between May 2008 and March 2009 was conducted. Women were screened for HIV-1 infection and syphilis, and interviewed regarding demographic, behavioral and obstetric data. Newborns to HIV-infected mothers were tested by b-DNA and DNA-PCR to detect HIV-1. RESULTS: A total 3300/8516 women were evaluated. Mean age was 25.8 ± 7.3 years. HIV-1 and syphilis seroprevalence rates were 0.84% (28/3300) and 0.51% (17/3300), respectively. HIV-1 infection was associated with: low education (p=0.04), having a partner with known HIV infection (p<0.0001) or with previous sexually transmitted infection (p<0.0001), blood transfusion (p=0.003), or accidental exposure to blood (p=0.003). Syphilis was associated with being Caucasian (p=0.02), having no steady partner (p=0.02), being a housewife (p=0.01), having an intravenous drug user (IVDU) sexual partner (p=0.04) or a sexual partner with previous STI (p<0.001). Higher education (p=0.04) was protective against HIV-infection. Attending a prenatal care program was protective against syphilis (p=0.008) and HIV-1 (p=0.02). No case of HIV-1 MTCT was detected, but 25% of children born to HIV-infected mothers were lost to follow up. CONCLUSIONS: In Salvador, peripartum prevalence of syphilis and HIV-1 infection among pregnant women were low, and associated with classic risk factors for both infections. The great proportion of very late diagnosis of HIV infection, and the high rate of loss of follow-up among positive mothers and their infants are of high concern.

Short communication: Use of raltegravir in late-presenting HIV-infected pregnant women.

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.

Anogenital infection by Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected men and women in Salvador, Brazil

ABSTRACT Background: Infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae are the most common bacterial sexually transmitted infections throughout the world. These sexually transmitted infections are a growing problem in people living with HIV/AIDS. However, the presence of these agents in extra genital sites, remains poorly studied in our country. The objective of this study was to estimate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae anal and genital infection in people living with HIV/AIDS followed in a reference center in Salvador, Brazil. Methods: Cross-sectional study, from June 2013 to June 2015. Proven HIV-infected people attending this reference center were invited. Clinical and epidemiological data were obtained through interview with standardized form. Chlamydia trachomatis and Neisseria gonorrhoeae screening was performed using qPCR (COBAS 4800® Roche). Results: The frequency of positive cases of Chlamydia trachomatis and Neisseria gonorrhoeae was 12.3% in total, 9.2% cases amongst women and 17.1% amongst men. We found 14.0% of positive cases in anus and 3.1% in genital region in men, while 5.6% and 3.6%, in women, respectively. Among men, anal infection was associated with age <29 years (p = 0.033), report of anal intercourse (p = 0.029), pain during anal intercourse (p = 0.028). On the other hand, no association between genital infection and other variables were detected in bivariate analysis. Among women, we detected an association between Chlamydia trachomatis genital infection and age <29 years (p < 0.001), younger age at first sexual intercourse (p = 0.048), pregnancy (p < 0.001), viral load >50 copies/mL (p = 0.020), and no antiretroviral use (p = 0.008). Anal infection in women was associated with age <29 years old (p < 0.001) and pregnancy (p = 0.023), and was not associated with report of anal intercourse (p = 0.485). Conclusion: Missed opportunities for diagnosis in extra genital sites could impact on HIV transmission. The extra genital sites need to be considered to break the HIV and bacterial sexually transmitted infections chain-of-transmission.

Syphilis and HIV-1 among parturient women in Salvador, Brazil: low prevalence of syphilis and high rate of loss to follow-up in HIV-infected women

BACKGROUND: The occurrence of syphilis and HIV-1 infections during pregnancy are major risks to the fetus due to mother-to-child transmission (MTCT). OBJECTIVES: To determine peripartum seroprevalence and risk factors of syphilis and HIV-1 infection among pregnant women in Salvador, Brazil, and the rate of HIV-1 MTCT. METHODS:Cross-sectional study of pregnant women who were admitted for delivery in a reference maternity hospital between May 2008 and March 2009 was conducted. Women were screened for HIV-1 infection and syphilis, and interviewed regarding demographic, behavioral and obstetric data. Newborns to HIV-infected mothers were tested by b-DNA and DNA-PCR to detect HIV-1. RESULTS: A total 3300/8516 women were evaluated. Mean age was 25.8 ± 7.3 years. HIV-1 and syphilis seroprevalence rates were 0.84% (28/3300) and 0.51% (17/3300), respectively. HIV-1 infection was associated with: low education (p = 0.04), having a partner with known HIV infection (p < 0.0001) or with previous sexually transmitted infection (p < 0.0001), blood transfusion (p = 0.003), or accidental exposure to blood (p = 0.003). Syphilis was associated with being Caucasian (p = 0.02), having no steady partner (p = 0.02), being a housewife (p = 0.01), having an intravenous drug user (IVDU) sexual partner (p = 0.04) or a sexual partner with previous STI (p < 0.001). Higher education (p = 0.04) was protective against HIV-infection. Attending a prenatal care program was protective against syphilis (p = 0.008) and HIV-1 (p = 0.02). No case of HIV-1 MTCT was detected, but 25% of children born to HIV-infected mothers were lost to follow up. CONCLUSIONS: In Salvador, peripartum prevalence of syphilis and HIV-1 infection among pregnant women were low, and associated with classic risk factors for both infections. The great proportion of very late diagnosis of HIV infection, and the high rate of loss of follow-up among positive mothers and their infants are of high concern.