Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

BackgroundAIDS Clinical Trial Group (ACTG) 5199 compared neurological and neuropsychological (NP) test performance of HIV-1+ participants in resource-limited settings (RLS) treated with three WHO recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes.MethodsStandardized neurological and brief NP examinations were administered to participants every 24 weeks. Generalized estimating equation (GEE) models assessed the association between TB with neurological and NP performance.ResultsCharacteristics of the 860 participants at baseline were: 53% female, 49% African; median age 34 years; CD4 of 173 cells/mm 3; and plasma HIV-1 RNA of 5.0 log c/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary (1 with both), and one case of CNS TB. Over the 192 weeks of follow-up after baseline there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB co-infection had significantly poorer performance on Grooved Pegboard (p< 0.001) and Fingertapping Non-Dominant hand (p<0.01). TB was associated with diffuse CNS disease (p<0.05). Furthermore, those with TB had 9.27 times (p< 0.001) higher odds of reporting decreased quality of life, and had 8.02 times (p= 0.0005) higher odds of loss of productivity.ConclusionsTB co-infection was associated with poorer neuropsychological functioning, particularly the fine motor skils, and had a substantial impact on functional ability and quality of life.Clinical Trials IdentifierNCT00096824 http://clinicaltrials.gov/ct2/show/NCT00096824?term=international+neurological&recr=Closed&type=Obsr&rank=1.

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV− participants from Brazil ( n = 240), India ( n = 480), Malawi ( n = 481), Peru ( n = 239), South Africa (480), Thailand ( n = 240), and Zimbabwe ( n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores ( p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

BACKGROUND AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. METHODS Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. RESULTS The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). CONCLUSIONS The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. CLINICAL TRIALS REGISTRATION NCT00096824.

Methods First, we have developed cryopreservation methods that allow infection of foreskin tissue explants after thawing (654 +/178.3 pg of p24/gr of tissue) and provide comparable infection rates to fresh samples( 716.5 +/446pg of p24/gr of tissue). Second, we have developed an ex vivo assay that uses human foreskin explants to replicate the polarized viral entry. After 12h of polarized exposure, HIV entering the explant is amplified for 6 days of culture with activated PBMCs and measured using p24 ELISA.

Introduction In the 26-year HIV/AIDS epidemic in Peru more than 39 682 cases of HIV and 25 533 cases of AIDS have been reported. Despite a higher concentration of the epidemic in men who have sex with men, there has been transmission to other groups and a decline in the male to female ratio of HIV infection. The objective of our study was to examine trends and factors associated with obtaining HIV testing for women of childbearing age (WCBA). Methods We used Demographic and Family Health Surveys databases of Peru from the years 2000, and 2004 to 2008 to study trends of self-reported HIV testing. The association between HIV testing and sociodemographic and reproductive health factors was assessed using bivariate analyses and logistic regression. Results We analysed data from 124 797 Peruvian WCBA. There was a significant difference in the number of WCBA who reported having been tested for HIV, with more than a doubling of testing between 2000 (15.3%) and 2008 (39.6%) (p<0.001). HIV testing was associated with urban residence (OR 1.96), higher educational level (OR 5.14), speaking Spanish (OR 3.10), having a partner (OR 3.21), self-perception of high risk for HIV (OR 1.41), and having had a sexually transmitted infection in the preceding year (OR 2.18). Conclusion There has been an increasing number of WCBA who report HIV testing since 2000, but less than half of WCBA do not seek HIV testing. Major factors associated with HIV testing should be considered when planning new initiatives to increase HIV testing of WCBA.

Objectives The NIMH Collaborative HIV/STD Intervention Trial implemented a 2-year intervention based on the theory of diffusion of innovations to decrease unprotected sex with non-primary partners among high-risk populations including heterosexually-identified, socially marginalised men in urban, coastal Peru. Methods 20 communities in 3 cities were randomised to the intervention or comparison arm. In intervention communities, 15% of the target population was trained as Community Popular Opinion Leaders (CPOLs) to deliver HIV prevention messages to their peers. In all communities, yearly assessments of the study cohort, independent of the intervention, gathered information on sexual behaviour, provided pre-test counselling, and testing for HIV/STIs at baseline, 1 year, and 2 years after randomisation. This analysis included the 2146 heterosexually-identified men who fulfilled the trial's inclusion criteria (frequented community social venues, were aged 18 to 40, and had sex in the past 6 months). Results Unprotected sex with a non-primary partner decreased by 10% in both study arms among heterosexually identified men. Almost half of the participants, in both the intervention and in the comparison arms, reported unprotected intercourse with a non-primary partner at the final follow-up (47.6% vs 48.7%, p=0.694) and there was no difference after controlling for baseline behaviour, OR 1.04, (95% CI 0.79—to 1.38). STI incidence was also did not differ by randomisation condition, IRR 1.14 (95% CI 0.77—to 1.68) comparing incidence in intervention vs control communities. Discussion We speculate that the lack of effect of the intervention among the heterosexually-identified men may be attributable to 1) an insufficiently strong intervention approach, 2) this group of men did not feel vulnerable to HIV or STI, or 3) the repeated biomedical testing and ancillary required counselling were as potent as the CPOL intervention. Future HIV prevention trials with this population should try to tailor the intervention to this group's risk perceptions and behaviours.

Commercial sex continues to play an integral role in the dissemination of sexually transmitted diseases (STD), including human immunodeficiency virus (HIV), to the general population. Governments across the world have taken health outreach measures to reduce STD in commercial sex workers. In Peru, female sex workers (FSW) can register with the Peruvian Ministry of Health to obtain free STD screening tests (including HIV testing) and gynecological examinations, free treatments, and safe sex counseling. In spite of such efforts, an undocumented number of FSW remain unregistered. In this study, we aim to characterize socio-demographics, sexual behaviors, and knowledge of sexually transmitted diseases of non-registered female sex workers. Also, we intend to examine the effectiveness of such governmental health initiatives as applied to the registered female sex workers (FSW) as we compare in Callao, Peru. A one-stage cluster-sample survey was conducted in Callao. Non-registered FSW were interviewed in randomly selected establishments at night time. A total of 45 women with a median age of 27 participated. Our results suggests that the non registered FSW have less recent health check ups and HIV testing, lower STD recognition, and use of condoms compared to registered FSW. In conclusion, this study suggests that public health efforts that target non-registered FSW are needed in Peru and should cover legal information, condom promotion, education, prevention, and medical management of STD.

With the objective of monitoring the distribution of HIV-1 subtypes and circulating recombinant forms (CRFs) in South America, population-based surveillance studies were performed in seven countries. Peripheral blood mononuclear cell, filter paper, fresh blood, and cocultivation samples were collected from HIV-positive patients from Colombia, Ecuador, Peru, Bolivia, Chile, Argentina, and Uruguay, during a 7-year period (1995-2001). DNA was prepared and HIV envelope subtypes were determined by heteroduplex mobility assay and DNA sequencing from 1289 HIV-positive samples. While subtypes B and F were the most commonly observed subtypes, two CRF02_AG strains were detected, in Ecuador. This is the first report of the existence of this CRF in South America.

Glucose-6-phosphatase confers on gluconeogenic tissues the capacity to release endogenous glucose in blood. The expression of its gene is modulated by nutritional mechanisms dependent on dietary fatty acids, with specific inhibitory effects of polyunsaturated fatty acids (PUFA). The presence of consensus binding sites of hepatocyte nuclear factor 4 (HNF4) in the -1640/+60 bp region of the rat glucose-6-phosphatase gene has led us to consider the hypothesis that HNF4alpha could be involved in the regulation of glucose-6-phosphatase gene transcription by long chain fatty acid (LCFA). Our results have shown that the glucose-6-phosphatase promoter activity is specifically inhibited in the presence of PUFA in HepG2 hepatoma cells, whereas saturated LCFA have no effect. In HeLa cells, the glucose-6-phosphatase promoter activity is induced by the co-expression of HNF4alpha or HNF1alpha. PUFA repress the promoter activity only in HNF4alpha-cotransfected HeLa cells, whereas they have no effects on the promoter activity in HNF1alpha-cotransfected HeLa cells. From gel shift mobility assays, deletion, and mutagenesis experiments, two specific binding sequences have been identified that appear able to account for both transactivation by HNF4alpha and regulation by LCFA in cells. The binding of HNF4alpha to its cognate sites is specifically inhibited by polyunsaturated fatty acyl coenzyme A in vitro. These data strongly suggest that the mechanism by which PUFA suppress the glucose-6-phosphatase gene transcription involves an inhibition of the binding of HNF4alpha to its cognate sites in the presence of polyunsaturated fatty acyl-CoA thioesters.

Objective To determine human immunodeficiency virus (HIV) seroprevalence in a sample of men who have sex with men (MSM) in Buenos Aires City and to identify risk factors associated with HIV type 1 infection.Methods Participants were invited to receive HIV counselling and testing at 'NEXO' (a gay non-governmental organization) by means of informative leaflets distributed in gay nightclubs, porno cinemas, gymnasiums, and in the streets. During the encounter, the study was explained by a trained social worker and individuals were invited to volunteer for the study. Diagnosis of HIV was performed using two screening tests and Western Blot assay was used as confirmatory.Results Human immunodeficiency virus was detected in 96 (13.8%; 95% CI: 11.4-16.7) of 694 MSM. Fourteen (14.6%) of the 96 HIV-positive MSM were already aware of their HIV serostatus. In univariate analysis, HIV-1 infection (odds ratio [OR] >1.5) was found to be associated with older age (30-39 years), being unemployed, a previous sexually transmitted disease (STD) history, and having an HIV-positive partner. Cocaine consumption and irregular use of condoms with occasional partners were also found to be risk factors. In multivariate logistic regression analysis, being unemployed (OR = 3.42; 95% CI: 1.17-9.99) and having an HIV-positive partner (OR = 2.67; 95% CI: 1.09-6.52) remained significant risk factors.Discussion The high HIV-1 prevalence observed suggests an urgent need for implementation of effective prevention campaigns. This represents the first cross-sectional epidemiological study of HIV among the high-risk group of MSM in Argentina.

Surveillance for HIV infection among people at increased risk was conducted in five countries in South America. Seroprevalence studies were conducted in more than 36,000 people in Ecuador, Peru, Boliva, Uruguay, and Argentina, along with genetic analysis of the HIV-1 strains. In all countries, the prevalence of HIV-1 among men who have sex with men (MSM) was high (3-30%), whereas the prevalence among female commercial sex workers (FCSMs) was low (0.3-6%). By envelope heteroduplex mobility assay, subtype B predominated in MSM communities and in FCSWs in Ecuador, Bolivia, and Peru. A new genetic screening assay, the multiregion hybridization assay for subtypes B and F (MHA-bf), was developed to improve large-scale genetic screening in South America. MHA-bf can screen four regions of the genome for subtype B or subtype F, and thus can detect most recombinants. The sensitivity of MHA-bf when applied to a panel of pure subtypes and CRF12_BF was 100%, and 88% of unique recombinants were also detected as recombinant. Using MHA-bf, more than 80% of samples from Ecuador, Peru, and Bolivia were classified as pure subtype B, whereas in Uruguay and Argentina this proportion was only 30 to 40%. BF recombinants were the most prevalent form of HIV-1 in Uruguay and Argentina. Subtype B is the most common subtype in countries lacking injecting drug use (IDU) epidemics, whereas BF recombinants are more common in countries where extensive IDU epidemics have been documented, suggesting the ontogeny of recombinant strains in particular risk groups in South America.