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Introduction: Prevention of mother to child transmission of HIV (PMTCT) is frequently challenged by irregular access to more effective anti-retroviral therapy. Nevirapine single dose (sdNVP), sdNVP+AZT+3TC for MTCT prophylaxis and NVP+ AZT+3TC for treatment and PMTCT were withdrawn due to low genetic resistance barrier and low efficacy. However current PMTCT lines in Mozambique include DTG+3TC+TDF, TDF+3TC+EFV, DTG +ABC+3TC, and AZT + NVP syrup prophylaxis for exposed babies. We assessed NVP hair and plasma concentrations and association with HIV-1RNA suppression among HIV+ ante-partum and post-partum women under PMTCT in Maputo, Mozambique., Methods: From December 2013 to November 2014, prospectively were enrolled 200 HIV+ ante-partum women on 200mg nevirapine and zidovudine 300 plus lamivudine 150mg twice daily at least with 3 months treatment and seen again at 24 weeks post-partum. Self-reported pill-taking adherence, NVP concentrations in hair, plasma, hemoglobin, CD4 cell count, HIV-1 RNA load was evaluated. NVP concentration in hair and plasma was analyzed as categorical quartile variable based on better data fit. NVP concentration was set between ≤3.77 ng/ml in plasma and ≤17,20 ng/mg in hair in quartile one to ≥5.36 ng/ml in plasma and ≥53.21 ng/mg in hair in quartile four. Logistic regression models for repeated measures were calculated. Following the World Health Organization (WHO) guidelines we set viral suppression at HIV-1RNA < 1000 c/mL. Outcome was HIV-1 RNA<1000 copies/ml. Predictor was NVP concentration in hair categorized in quartiles., Results: In total 369 person-visits (median of 1.85) were recorded. Self-reported adherence was 98% (IQR 97-100%) at ante-partum. In 25% person visits, NVP concentrations were within therapeutic levels (3.77 ng/ml to 5.35 ng/ml) in plasma and (17.20 ng/mg to 53.20 ng/mg) in hair. In 50% person visits NVP concentrations were above 5.36 ng/ml in plasm and 53.21 ng/mg in hair. HIV-1 RNA suppression was found in 34.7% of women with two viral loads, one at enrollment and another in post-partum. Odds of HIV-1 RNA suppression in quartile 4, was about 6 times higher than in quartile 1 (p-value = 0.006) for NVP hair concentration and 7 times for NVP plasma concentration (p-value = 0.012)., Conclusions: The study results alert for potential low efficacy of current PMTCT drug regimens in use in Mozambique. Affordable means for individual monitoring adherence, ART plasma and hair levels, drug resistant and HIV-1 RNA levels monitoring are recommended for prompt identification of inadequate drug regimens exposure patterns and adjust accordingly., Competing Interests: The authors have declared that no competing interests exist.

Recent studies suggest that a large proportion of new HIV-1 infections in mature epidemics occurs within discordant couples, making discordancy a major contributor to the spread of HIV/AIDS in Africa. This paper aims at assessing changes over a five-year period (2009-2015) on the (risk) factors associated with HIV serodiscordance among couples in Mozambique, using cross-sectional data from the INSIDA and IMASIDA surveys. The pooled data of both surveys were analyzed using a joint model for three parameters characterizing in a particular way disagreement and sero(con/dis)corance between the HIV statuses of couples, as introduced by Aerts et al.: the probability that the female partner is HIV positive, given that both partners differ in their HIV status, the probability that only one partner is HIV positive, given that at least one of the two partners is positive ("positive" serodiscordance), and the probability that both partners are negative given that at most one of the two partners is positive ("negative" seroconcordance). The results reveal similar significant factors and estimates as in Aerts et al. (HIV prevalence, union number for woman, STI for man, condom use by woman and wealth index), but the additional significant factors "condom use by man" (no use had a negative effect on the positive serodiscordance) and "union number for man" (for couples where the man has been married or co-habiting with a woman before had a decreased negative seroconcordance) were identified. The only factor that had a different effect over time (IMASIDA as compared to INSIDA) was the effect of "HIV prevalence of province" on the negative seroconcordance. The negative effect of a higher HIV prevalence was less pronounced in 2015 for negative seroconcordance., Competing Interests: The authors have declared that no competing interests exist.

Maternal mortality remains very high in Mozambique, with estimates from 2015 showing a maternal mortality ratio of 489 deaths per 100,000 live births, even though the rates tend to decrease since 1990. Pregnancy related hemorrhage, gestational hypertension and diseases such as malaria and HIV/AIDS are amongst the leading causes of maternal death in Mozambique, and a significant number of these deaths occur within health facilities. Often, the analysis of data on maternal mortality involves the use of counts of maternal deaths as outcome variable. Previously we showed that a class of hierarchical zero-inflated models were very successful in dealing with overdispersion and clustered counts when analyzing data on maternal deaths and related risk factors within health facilities in Mozambique. This paper aims at providing additional insights over previous analyses and presents an extension of such models to account for spatial variation in a disease mapping framework of facility-based maternal mortality in Mozambique., Competing Interests: The authors have declared that no competing interests exist.

G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways.

Whereas the number of people newly infected by HIV is continuing to decline globally, the epidemic continues to expand in many parts of the world. As the HIV/AIDS epidemic has matured in many countries, it is believed that the proportion of new infections occurring within couples has risen. Across countries, including Mozambique, a sizeable proportion of couples with HIV infection are discordant. A serodiscordant couple is a couple in which one partner has tested positive for HIV and the other has not. To describe the HIV serodiscordance among couples, a variety of association measures can be used. In this paper, we propose the serodiscordance measure (SDM) as a new alternative measure. Focus is on the specification of flexible marginal and random effects models for multivariate correlated binary data together with a full-likelihood estimation method, to adequately and directly describe the measure of interest. Fitting joint models allows examining the effects of different risk factors and other covariates on the probability to be HIV positive for each member within a couple, and estimating common effects for both probabilities more efficiently, while accounting for the association between their infection status. Moreover, the interpretation of the proposed association parameter SDM is more direct and relevant and effects of covariates can be studied as well. Results show that the HIV prevalence for the province where a couple was located as well as the union number for the woman within a couple are factors associated with HIV serodiscordance. These findings are important for the Mozambican public health policy makers to design national prevention plans, which include policies to stimulate regular HIV testing for couples as well as adolescents and young adults, prior to getting married or living together as a couple.

Background: Prevalence of HIV in Mozambique among individuals aged 15-49 years is 11.5%. The HIV prevalence is higher in women than in men across the country, peaking at ages 25-29 years and 35-39 years, respectively. In this study, we aimed at determining the prevalence and incidence of HIV, prevalence of Hepatitis B (HBV), and prevalence of syphilis in youths. We also characterized a cohort of youths for future participation in phase I/II HIV vaccine trials., Methods: The study was conducted at a youth clinic in Maputo Central Hospital from August 2009 to October 2011. Youths of both genders aged 18-24 years (n = 1380) were screened for HIV using a sequential algorithm of two immunochromatographic assays, HBV using an enzyme linked immunosorbant test, and syphilis using a treponemal immunochromatographic strip test. The HIV seronegative participants (n = 1309) were followed-up for 12 months with quarterly study visits. The clinical and behavioral data were collected using structured questionnaires. The HIV seroconversions were confirmed by a molecular assay., Results: The study population was female dominant (76.8%). All participants had a formal education, with 44.6% studying for technical or higher education degrees. The mean age at sexual debut was 16.6 years (SD: ± 1.74), with 85.6% reporting more than one sexual partner in life. The screening showed the prevalence of HIV, HBV, and syphilis at 5.1% (95% CI: 3.97-6.31), 12.2% (95% CI 10.5%-14.0%), and 0.36% (95% CI 0.15%-0.84%), respectively. The HIV incidence rate was found to be 1.14/100 person years (95% CI: 0.67-1.92). Retention rates were stable throughout the study being 85.1% at the last visit., Conclusion: Incidence of HIV in this cohort of youths in Maputo was relatively low. Also, the prevalence of HIV and syphilis was lower than the national values in this age group. However, the HBV prevalence was higher than in previous reports in the country.

Background: Clinical laboratory reference values from North American and European populations are currently used in most Africans countries due to the absence of locally derived reference ranges, despite previous studies reporting significant differences between populations. Our aim was to define reference ranges for both genders in 18 to 24 year-old Mozambicans in preparation for clinical vaccine trials., Methods: A cross-sectional study including 257 volunteers (102 males and 155 females) between 18 and 24 years was performedat a youth clinic in Maputo, Mozambique. All volunteers were clinically healthy and human immunodeficiency virus, Hepatitis B virus and syphilis negative.Median and 95% reference ranges were calculated for immunological, hematological and chemistry parameters. Ranges were compared with those reported based on populations in other African countries and the US. The impact of applying US NIH Division of AIDS (DAIDS) toxicity tables was assessed., Results: The immunology ranges were comparable to those reported for the US and western Kenya.There were significant gender differences in CD4+ T cell values 713 cells/µL in males versus 824 cells/µL in females (p<0.0001). Hematologic values differed from the US values but were similar to reports of populations in western Kenya and Uganda. The lower and upper limits of the ranges for hemoglobin, hematocrit, red blood cells, white blood cells and lymphocytes were somewhat lower than those from these African countries. The chemistry values were comparable to US values, with few exceptions. The upper limits for ALT, AST, bilirubin, cholesterol and triglycerides were higher than those from the US. DAIDStables for adverse events predicted 297 adverse events and 159 (62%) of the volunteers would have been excluded., Conclusion: This study is the first to determine normal laboratory parameters in Mozambique. Our results underscore the necessity of establishing region-specific clinical reference ranges for proper patient management and safe conduct of clinical trials.