Risk Factors for Delayed Viral Suppression on First-Line Antiretroviral Therapy among Persons Living with HIV in Haiti, 2013-2017

Studies of viral suppression on first-line antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLHIV) in Haiti are limited, particularly among PLHIV outside of the Ouest department, where the capital Port-au-Prince is located. This study described the prevalence and risk factors for delayed viral suppression among PLHIV in all geographic departments of Haiti between 2013 and 2017. Individuals who received viral load testing 3 to 12 months after ART initiation were included. Data on demographics and clinical care were obtained from the Haitian Active Longitudinal Tracking of HIV database. Multivariable logistic regression was performed to predict delayed viral suppression, defined as a viral load ≥1000 HIV-1 RNA copies/mL after at least 3 months on ART. Viral load test results were available for 3,368 PLHIV newly-initiated on ART. Prevalence of delayed viral suppression was 40%, which is slightly higher than previous estimates in Haiti. In the multivariable analysis, delayed viral suppression was significantly associated with younger age, receiving of care in the Ouest department, treatment with lamivudine (3TC), zidovudine (AZT), and nevirapine (NVP) combined ART regimen, and CD4 counts below 200 cells/mm3. In conclusion, this study was the first to describe and compare differences in delayed viral suppression among PLHIV by geographic department in Haiti. We identified populations to whom public health interventions, such as more frequent viral load testing, drug resistance testing, and ART adherence counseling should be targeted

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged 50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection

Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs)

It has long been axiomatic that a protein’s structure determines its function. Intrinsically disordered proteins (IDPs) and disordered protein regions (IDRs) defy this structure–function paradigm. They do not exhibit stable secondary and/or tertiary structures and exist as dynamic ensembles of interconverting conformers with preferred, nonrandom orientations.(1-4) The concept of IDPs and IDRs as functional biological units was initially met with skepticism. For a long time, disorder, intuitively implying chaos, had no place in our perception of orchestrated molecular events controlling cell biology. Over the past years, however, this notion has changed. Aided by findings that structural disorder constitutes an ubiquitous and abundant biological phenomenon in organisms of all phyla,(5-7) and that it is often synonymous with function,(8-11) disorder has become an integral part of modern protein biochemistry. Disorder thrives in eukaryotic signaling pathways(12) and functions as a prominent player in many regulatory processes.(13-15) Disordered proteins and protein regions determine the underlying causes of many neurodegenerative disorders and constitute the main components of amyloid fibrils.(16) They further contribute to many forms of cancer, diabetes and to cardiovascular and metabolic diseases.(17, 18) Research into disordered proteins produced significant findings and established important new concepts. On the structural side, novel experimental and computational approaches identified and described disordered protein ensembles(3, 19, 20) and led to terms such as secondary structure propensities, residual structural features, and transient long-range contacts.(1, 21) The discovery of coupled folding-and-binding reactions defined the paradigm of disorder-to-order transitions(22) and high-resolution insights into the architectures of amyloid fibrils were obtained.(23, 24) On the biological side, we learned about the unexpected intracellular stability of disordered proteins, their roles in integrating post-translational protein modifications in cell signaling and about their functions in regulatory processes ranging from transcription to cell fate decisions.(15, 25, 26) One open question remaining to be addressed is how these in vitro structural insights relate to biological in vivo effects. How do complex intracellular environments modulate the in vivo properties of disordered proteins and what are the implications for their biological functions (Figure 1)?(27-29

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

International audienceImpairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo