Enhanced Antiretroviral treatment support in relation to Quality of Life and Virological failure in low income setting : A cluster randomized controlled trial in Quang Ninh, Vietnam

Background Antiretroviral therapy (ART) has become more widely available in Vietnam since 2005. However, up to now, very little is known about characteristics of people living with HIV (PLHIV) at ART initiation including factors influencing ART adherence. On the other hand, scaling up HIV care in Vietnam faces challenges, including shortages of health care personnel willing to work with HIV-infected individuals resulting in heavy workloads and constrained support to patient adherence. To counter this, community-based peer support interventions have sought to improve adherence to ART, to lessen internal HIV-related stigma as well as to improve treatment outcomes. Aim The overall aim of this thesis is to assess the effect of enhanced treatment support on treatment outcomes including Immunological and Virological failure as well as Quality of Life among PLHIV on ART in, Quang Ninh, Vietnam. The aim of study (paper) I was to explore factors influencing adherence to antiretroviral therapy and to assess possible intervention strategies to enhance ART adherence. The aim of study II was to describe patient characteristics at baseline with an emphasis on sero-discordance among married patients. The aim of study III was to assess the impact of peer support on quality of life after one year follow up. The aim of study IV was to assess the effect of the peer support intervention on adherence as well as immunological and virological failure after 2 years of follow up. Methods Data for the thesis was collected in Quang Ninh, a province in Northern Vietnam, and was organized into four studies (I-IV). In study I a qualitative approach was used through focus group discussions with persons living with HIV and their family members. Based on the findings from study I, an intervention strategy was developed engaging PLHIV to support adherence, peer support, with home visits twice a week the first two months and thereafter weekly. Study II, III and IV were based on a cluster randomized controlled trial to assess the effect of peer support on quality of life (QOL) as well as adherence, immunological and virological treatment failure among 640 PLHIV initiating ART in 4 districts in Quang Ninh. In study II, a baseline structured questionnaire was used to assess characteristics of patients initiating ART. In study III a structured questionnaire was used to assess QOL (WHOQOL-HIVBREF) which was conducted every four months. In study IV the adherence assessment was done using a modified AACTG structured questionnaire which was carried out every 3 months, immunological and virological failure were assessed using CD4 count and viral load (Exavir Load) every 6 months. Findings In study I, stigma was described as the main barrier to ART adherence, causing patients to delay their ART medications of fear of unintentional disclosure. The preferred support to enhance adherence among patients was community-based peer-support by other PLHIV who had received sufficient training. Study II showed that PLHIV initiating ART in Quang Ninh generally had severe immunosuppression and males presented with more severe immunosuppression than females. Of male patients, the majority (70%) reported a history of heroin use and HIV transmission through sharing needles, among females the majority reported sexual transmission (95%). The sero-discordance rate among the married patients was in total 58%, significantly higher among men compared to women (71% vs. 18%). Factors associated with a high rate of sero-discordance were injection drug use (IDU) history, tuberculosis (TB) history and the availability of voluntary counseling and testing (VCT) in residential locations. High sero-concordance was associated with college/university education. In study III, there was a significantly higher QOL rating in the peer support intervention group compared to the control group after 12 months follow up among patients who were enrolled on ART with severe immunosuppression but not for patients enrolled with mild or no clinical symptoms. The peer support intervention did not have any effect on Internal AIDS-related stigma. Study IV showed no significant difference between intervention and control group on self-reported adherence, virological and immunological failure rates after 2 years of follow up. High VL at baseline is a predictor for both VL failure and CD4 trends (IV). Conclusions: Stigma is reported to be a main obstacle to HIV treatment adherence. To prevent HIV transmission among sero-discordant couples measures should be taken including increased information, provision of condoms as well as ART to the HIV positive partner regardless of CD4 count. Peer support has a positive impact on QOL among patients initiating ART severely immune-compromised. Peer support did not show any significant effect on self-reported adherence, virological and immunological failure rates after 2 year of follow up. The results suggest adherence support measures for PLHIV on ART should be contextualized according to individual, clinical and social needs

Improving the representation of hydrological connectivity in conceptual models

Understanding hydrological connectivity is one of the main objectives in hydrological research. Hydrological models have been proved to be an efficient tool for a better understanding of hydrological connectivity. Conceptual models have shown certain advantages compared to physically-based distributed models in terms of data requirement and computational time. However, the hydrological connectivity in conceptual models is usually not well represented. In this study, the Soil and Water Assessment Tool (SWAT) was selected for further improvements to have a better representation and simulation of hydrological connectivity. SWAT is a semi-distributed hydrological model used to simulate the effect of land use management practices on water, sediment, and nutrient yields at a basin scale. SWAT has been tested and applied worldwide. However, the non-spatial characteristic of the hydrologic response unit (HRU) concept used in SWAT has been identified as one of the main disadvantages for modeling hydrological connectivity. In this study, the hydrologic routing subroutine of SWAT was examined and the groundwater subroutine was modified to account for hydrological connectivity in porous and karst-dominated aquifers. Results show that the current hydrologic routing subroutines of SWAT are not able to simulate hydrological connectivity between river segments in the river network. The Muskingum routing method in SWAT could (1) cause unphysical oscillations in the simulated streamflow and (2) overestimate the evapotranspiration loss in the river and results in a hydrologic disconnectivity during low flow periods. For improving the representation of hydrological connectivity in the subsurface porous aquifer, the multicell aquifer model was proposed and incorporated into SWAT. The modified model, the so-called SWAT-MCA model, was validated in two basins located in Niedersachsen, Germany. The results show that the SWAT-MCA model could well simulate the regional groundwater flow and return flow from aquifer to stream. For improving the representation of hydrological connectivity in the karst-dominated aquifer due to interbasin groundwater flow (IGF) was added to SWAT, the SWAT_IGF was developed. The developed model was applied in a karst area located in the Southwest Harz Mountains, Germany. The model was validated with the observed streamflow and spring flow. Results show that the SWAT_IGF could well represent the hydrological connection due to interbasin groundwater flow in karst areas. The modified models, SWAT-MCA and SWAT_IGF could be applied for other regions to regional groundwater flow in porous aquifer and IGF in karst-dominated aquifers

Control of Alternaria alternata, Causal Agent of Dead (Dormant) Flower Bud Disease of Pear

Dead (dormant) flower buds of pear are an important phenomenon in pear production in the Netherlands. Vigourous or unbalanced tree growth and Pseudomonas syringae pv. syringae (P.s.s.) are mentioned as likely causes of dead flower buds. Pseudomonas syringae pv. syringae was occasionally isolated from diseased flower buds. However, Alternaria alternata was nearly always isolated from diseased buds and also often in symptomless flower buds. By identifying the causal agent of dead flower buds disease, an effective control strategy can be developed. In field trials it was proven that fungicide treatments can reduce disease incidences significantly

MicroRNA-155 is induced during the macrophage inflammatory response

The mammalian inflammatory response to infection involves the induction of several hundred genes, a process that must be carefully regulated to achieve pathogen clearance and prevent the consequences of unregulated expression, such as cancer. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators that has also been linked to cancer. However, the relationship between inflammation, innate immunity, and miRNA expression is just beginning to be explored. In the present study, we use microarray technology to identify miRNAs induced in primary murine macrophages after exposure to polyriboinosinic:polyribocytidylic acid or the cytokine IFN-{beta}. miR-155 was the only miRNA of those tested that was substantially up-regulated by both stimuli. It also was induced by several Toll-like receptor ligands through myeloid differentiation factor 88- or TRIF-dependent pathways, whereas up-regulation by IFNs was shown to involve TNF-{alpha} autocrine signaling. Pharmacological inhibition of the kinase JNK blocked induction of miR-155 in response to either polyriboinosinic:polyribocytidylic acid or TNF-{alpha}, suggesting that miR-155-inducing signals use the JNK pathway. Together, these findings characterize miR-155 as a common target of a broad range of inflammatory mediators. Importantly, because miR-155 is known to function as an oncogene, these observations identify a potential link between inflammation and cancer