Anna Hakobyan

Unmet Need for Family Planning, Contraceptive Failure, and Unintended Pregnancy among HIV-Infected and HIV-Uninfected Women in Zimbabwe

Background Prevention of unintended pregnancies among women living with HIV infection is a strategy recommended by the World Health Organization for prevention of mother-to-child transmission of HIV (PMTCT). We assessed pregnancy intentions and contraceptive use among HIV-positive and HIV-negative women with a recent pregnancy in Zimbabwe. Methods We analyzed baseline data from the evaluation of Zimbabwe’s Accelerated National PMTCT Program. Eligible women were randomly sampled from the catchment areas of 157 health facilities offering PMTCT services in five provinces. Eligible women were ≥16 years old and mothers of infants (alive or deceased) born 9 to 18 months prior to the interview. Participants were interviewed about their HIV status, intendedness of the birth, and contraceptive use. Results Of 8,797 women, the mean age was 26.7 years, 92.8% were married or had a regular sexual partner, and they had an average of 2.7 lifetime births. Overall, 3,090 (35.1%) reported that their births were unintended; of these women, 1,477 (47.8%) and 1,613 (52.2%) were and were not using a contraceptive method prior to learning that they were pregnant, respectively. Twelve percent of women reported that they were HIV-positive at the time of the survey; women who reported that they were HIV-infected were significantly more likely to report that their pregnancy was unintended compared to women who reported that they were HIV-uninfected (44.9% vs. 33.8%, p<0.01). After adjustment for covariates, among women with unintended births, there was no association between self-reported HIV status and lack of contraception use prior to pregnancy. Conclusions Unmet need for family planning and contraceptive failure contribute to unintended pregnancies among women in Zimbabwe. Both HIV-infected and HIV-uninfected women reported unintended pregnancies despite intending to avoid or delay pregnancy, highlighting the need for effective contraceptive methods that align with pregnancy intentions.

Evaluating the Impact of Zimbabwe’s Prevention of Mother-to-Child HIV Transmission Program: Population-Level Estimates of HIV-Free Infant Survival Pre-Option A

Objective We estimated HIV-free infant survival and mother-to-child HIV transmission (MTCT) rates in Zimbabwe, some of the first community-based estimates from a UNAIDS priority country. Methods In 2012 we surveyed mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. Enrolled infants were born 9–18 months before the survey. We collected questionnaires, blood samples for HIV testing, and verbal autopsies for deceased mothers/infants. Estimates were assessed among i) all HIV-exposed infants, as part of an impact evaluation of Option A of the 2010 WHO guidelines (rolled out in Zimbabwe in 2011), and ii) the subgroup of infants unexposed to Option A. We compared province-level MTCT rates measured among women in the community with MTCT rates measured using program monitoring data from facilities serving those communities. Findings Among 8568 women with known HIV serostatus, 1107 (12.9%) were HIV-infected. Among all HIV-exposed infants, HIV-free infant survival was 90.9% (95% confidence interval (CI): 88.7–92.7) and MTCT was 8.8% (95% CI: 6.9–11.1). Sixty-six percent of HIV-exposed infants were still breastfeeding. Among the 762 infants born before Option A was implemented, 90.5% (95% CI: 88.1–92.5) were alive and HIV-uninfected at 9–18 months of age, and 9.1% (95%CI: 7.1–11.7) were HIV-infected. In four provinces, the community-based MTCT rate was higher than the facility-based MTCT rate. In Harare, the community and facility-based rates were 6.0% and 9.1%, respectively. Conclusion By 2012 Zimbabwe had made substantial progress towards the elimination of MTCT. Our HIV-free infant survival and MTCT estimates capture HIV transmissions during pregnancy, delivery and breastfeeding regardless of whether or not mothers accessed health services. These estimates also provide a baseline against which to measure the impact of Option A guidelines (and subsequently Option B+).

Option A improved Hiv-free infant survival and mother to child Hiv transmission at 9–18 months in Zimbabwe

Objective: We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Design: Serial cross-sectional community-based serosurveys. Methods: We analyzed serosurvey data collected in 2012 and 2014 among mother–infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9–18 months before each survey to mothers at least 16 years old. We randomly selected mother–infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. Results: We analyzed 7249 mother–infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was −5.2 percentage points (95% confidence interval = −8.1, −2.3, P < 0.001). The mean difference in the catchment area level HIV-free survival was 5.5 percentage points (95% confidence interval = 2.6, 8.5, P < 0.001). Between 2012 and 2014, 1779 infant infections were averted compared with the pre-Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). Conclusion: We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9–18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwes remarkable progress toward eMTCT.

Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles

Introduction Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations. The mechanisms involved in their initiation and development remain poorly understood, however the existence of some clear similarities between autoimmune and autoinflammatory disorders indicates variable degrees of interaction between immune-related mechanisms. Methods Our study aims at contributing to a holistic, pathway-centered view on the inflammatory condition of autoimmune and autoinflammatory diseases. We have evaluated similarities and specificities of pathway activity changes in twelve autoimmune and autoinflammatory disorders by performing meta-analysis of publicly available gene expression datasets generated from peripheral blood mononuclear cells, using a bioinformatics pipeline that integrates Self Organizing Maps and Pathway Signal Flow algorithms along with KEGG pathway topologies. Results and conclusions The results reveal that clinically divergent disease groups share common pathway perturbation profiles. We identified pathways, similarly perturbed in all the studied diseases, such as PI3K-Akt, Toll-like receptor, and NF-kappa B signaling, that serve as integrators of signals guiding immune cell polarization, migration, growth, survival and differentiation. Further, two clusters of diseases were identified based on specifically dysregulated pathways: one gathering mostly autoimmune and the other mainly autoinflammatory diseases. Cluster separation was driven not only by apparent involvement of pathways implicated in adaptive immunity in one case, and inflammation in the other, but also by processes not explicitly related to immune response, but rather representing various events related to the formation of specific pathophysiological environment. Thus, our data suggest that while all of the studied diseases are affected by activation of common inflammatory processes, disease-specific variations in their relative balance are also identified.

Application of MATLAB in -Omics and Systems Biology

Biological data analysis has dramatically changed since the introduction of highthroughput -omics technologies, such as microarrays and next-generation sequencing. The key advantage of obtaining thousands of measurements from a single sample soon became a bottleneck limiting transformation of generated data into knowledge. It has become apparent that traditional statistical approaches are not suited to solve problems in the new reality of “big biological data.” From the other side, traditional computing languages such as C/C++ and Java, are not flexible enough to allow for quick develop‐ ment and testing of new algorithms, while MATLAB provides a powerful computing environment and a variety of sophisticated toolboxes for performing complex bioinfor‐ matics calculations. We have used MATLAB to develop the pathway signal flow (PSF) algorithm for assessment of pathway activity changes based on high-throughput gene expression and pathway topologies. Additionally, we have created a KEGGParser tool for parsing, editing, and visualizing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps. We have used these tools to obtain a collection of KEGG pathways and evaluate their activity changes in different clinical forms of pulmonary sarcoidosis (PS). The application of PSF provided an extended systems view on pathway deregulation states and implicated several new pathways in sarcoidosis that had not been identified using other analysis approaches.

Quantitative trait association study for mean telomere length in the South Asian genomes

MOTIVATION Mean telomere length (MTL) is associated with cancers and age-related diseases, which necessitates identification of genomic and environmental factors that impact telomere length dynamics. Here, we present a pilot genome wide association (GWA) study for MTL in South Asian population using publicly available next generation whole genome sequences (WGS), both for MTL and genotype calculations. RESULTS MTL in the studied population was not correlated with age, which is in accordance with previous reports. Further, we identified that individuals with Sikh religion had longer telomeres, which may be the result of complex interaction between genetic background and environmental factors. Finally, we identified 51 MTL-associated SNPs residing in five loci. The top ones were located in ADARB2 gene, which has previously been implicated with extreme old age. CONCLUSION Our results show that WGS data can be used in telomere length studies. In addition, we introduce novel loci implicated in MTL that may be worth considering in further telomere studies. CONTACT aarakelyan@sci.am SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Fragile Sites as Drivers of Gene and Genome Evolution

Purpose of ReviewAlthough the detailed composition of the human genome is known base by base for its major part, the orchestration of and which elements exactly facilitate organization and flexibility of higher order gene and genome architecture, are poorly understood and scarcely studied.Recent FindingsThis review focuses on fragile sites (FSs). They are considered as regions of chromosome breakage with overlapping signatures for breakpoints observed repeatedly in tumor and constitutional rearrangements, and also in evolutionary conserved breakpoints. Thus, FSs are promising targets to study and get deeper insights into chromosome, gene, and genome evolution.SummaryHere, we summarize the current knowledge on FSs and their correlation with aforementioned breakpoint categories. Based on that, we introduce a new model for FSs driven gene and genome evolution, which also can explain the recently observed spreading of (pseudo-)gene family members among the human genome. FSs therefore may provide an “infrastructure” to distribute gene copies onto different sites of the genome and may be the underlying cause for formation of gene families.