When Should Children with HIV Infection Be Started on Antiretroviral Therapy?

Background to the debate: The advent of highly active antiretroviral therapy (HAART) dramatically improved the prognosis for both adults and children infected with HIV who had access to treatment. However, the optimal timing for initiating treatment remains controversial, particularly in children. This debate lays out the case for deferred treatment against the case for early initiation of HAART in children.     

What Happens to Patients on Antiretroviral Therapy Who Transfer Out to Another Facility?

Background

Long term retention of patients on antiretroviral therapy (ART) in Africa''s rapidly expanding programmes is said to be 60% at 2 years. Many reports from African ART programmes make little mention of patients who are transferred out to another facility, yet Malawi''s national figures show a transfer out of 9%. There is no published information about what happens to patients who transfer-out, but this is important because if they transfer-in and stay alive in these other facilities then national retention figures will be better than previously reported.

Methodology/Principal Findings

Of all patients started on ART over a three year period in Mzuzu Central Hospital, North Region, Malawi, those who transferred out were identified from the ART register and master cards. Clinic staff attempted to trace these patients to determine whether they had transferred in to a new ART facility and their outcome status. There were 805 patients (19% of the total cohort) who transferred out, of whom 737 (92%) were traced as having transferred in to a new ART facility, with a median time of 1.3 months between transferring-out and transferring-in. Survival probability was superior and deaths were lower in the transfer-out patients compared with those who did not transfer.

Conclusion/Significance

In Mzuzu Central Hospital, patients who transfer-out constitute a large proportion of patients not retained on ART at their original clinic of registration. Good documentation of transfer-outs and transfer-ins are needed to keep track of national outcomes. Furthermore, the current practice of regarding transfer-outs as being double counted in national cohorts and subtracting this number from the total national registrations to get the number of new patients started on ART is correct.     

Weight-Loss Strategies Used by the General Population: How Are They Perceived?

Background

The rising prevalence of obesity and the social pressure for thinness increase the prevalence of dieting. However, little is known about the overall perception of dieting strategies actually used by the general population.

Objectives

Our main objective was to investigate perceptions of weight-loss practices in an observational study in order to identify the most favourable strategy.

Design

Adults from the ongoing Nutrinet-Santé cohort study who had reported engaging in dieting in the three previous years were included in the study. For each diet, detailed information was collected on types of diets, circumstances and perception of the diet, and outcomes. Perceptions were compared across diets using sex-specific mixed effects models.

Result

Among the 48 435 subjects who had completed the respective questionnaire, 12 673 (26.7%, 87.8% of women) had followed at least one weight-loss diet in the previous three years. Diet plans prescribed by health professionals and diets conforming to official dietary recommendations were the most favourably perceived among all assessed weight-loss strategies. Alternatively, commercial diet plans and self-imposed dietary restrictions were more negatively perceived (Odds ratios (OR) for adherence difficulty 1.30 (95% confidence interval (0.99;1.7)) in men and OR 1.92 (1.76;2.10) in women compared to official nutritional guidelines; OR 1.06 (0.82;1.38) in men and OR 1.39 (1.26;1.54) in women respectively) compared to official nutritional guidelines.

Conclusion

Official dietary recommendations could be useful tools for maintaining a dietary balance while following a weight-loss diet.     

As Good As It Gets? The Problem of HIV Persistence despite Antiretroviral Drugs

Human immunodeficienty virus (HIV) infection is suppressed but not eliminated by antiretroviral drugs.?Viral?persistence in the face of therapy has been explained by viral latency, lowered effectiveness of drugs?in some anatomical sites and cell types, and cell-to-cell spread. These mechanisms allow for drug-sensitive virus to persist despite treatment. Understanding the persistence mechanism at work at?different times after infection, including the time of initial infection immediately following transmission?when reservoirs are first formed, will reveal if we are at the limit of what can be achieved with the?current therapy paradigm of suppressing ongoing virus replication with drugs. We discuss some of?the possible reasons why HIV persists at different points on the infection timeline, focusing on the?role ongoing replication may have in maintaining the infection despite drugs at early times postexposure.     

Veterans’ Perspectives on Interventions to Improve Retention in HIV Care

Poor retention in HIV medical care is associated with increased mortality among patients with HIV/AIDS. Developing new interventions to improve retention in HIV primary care is needed. The Department of Veteran Affairs (VA) is the largest single provider of HIV care in the US. We sought to understand what veterans would want in an intervention to improve retention in VA HIV care. We conducted 18 one-on-one interviews and 15 outpatient focus groups with 46 patients living with HIV infection from the Michael E. DeBakey VAMC (MEDVAMC). Analysis identified three focus areas for improving retention in care: developing an HIV friendly clinic environment, providing mental health and substance use treatment concurrent with HIV care and encouraging peer support from other Veterans with HIV.     

HIV Status Disclosure to Sexual Partners,among People Living with HIV and AIDS on Antiretroviral Therapy at Sokodé Regional Hospital,Togo

BackgroundMany studies have reported factors associated with HIV status disclosure among People Living With HIV and AIDS (PLWHA) but very few were conducted among PLWHA receiving ART. In Togo, no study on HIV status disclosure to sexual partners has been conducted among PLWHA on ART yet. We sought to document factors associated with HIV status disclosure among PLWHA receiving ART at Sokodé regional hospital in Togo.MethodThis was a cross-sectional study conducted from May to July 2013 at the regional hospital of Sokodé among 291 PLWHA who had been on ART for at least three months.ResultsA total of 291 PLWHA on ART were enrolled in this study. Their mean age (±SD) was 37.3±9.3 years and the sex ratio (Male/Female) was 0.4. Among them, 215 (74.6%) completed the questionnaire on HIV sero-status disclosure. We found that 131 PLWHA (60.9%) had disclosed their HIV sero-status to their sexual partners; 130 (60.5%) were aware of the HIV status of their sexual partners. In the multivariate analysis, the factors associated with HIV status disclosure to sexual partners were: adherence to ART (aOR = 4.89; 95%CI = [1.52; 15.78]), sexual partner awareness of HIV sero-status (aOR = 52.73; 95%CI = [14.76; 188.36]) and marital status of PLWHA (aOR = 6.10; 95%CI = [1.74; 21.37]).ConclusionThis study allowed us to note that the disclosure of HIV status to sexual partners is relatively low and to document the associated factors such as adherence to ART, sexual partner awareness of HIV sero-status and marital status.     

How Many Genetic Variants Remain to Be Discovered?

A great majority of genetic markers discovered in recent genome-wide association studies have small effect sizes, and they explain only a small fraction of the genetic contribution to the diseases. How many more variants can we expect to discover and what study sizes are needed? We derive the connection between the cumulative risk of the SNP variants to the latent genetic risk model and heritability of the disease. We determine the sample size required for case-control studies in order to achieve a certain expected number of discoveries in a collection of most significant SNPs. Assuming similar allele frequencies and effect sizes of the currently validated SNPs, complex phenotypes such as type-2 diabetes would need approximately 800 variants to explain its 40% heritability. Much smaller numbers of variants are needed if we assume rare-variants but higher penetrance models. We estimate that up to 50,000 cases and an equal number of controls are needed to discover 800 common low-penetrant variants among the top 5000 SNPs. Under common and rare low-penetrance models, the very large studies required to discover the numerous variants are probably at the limit of practical feasibility. Under rare-variant with medium- to high-penetrance models (odds-ratios between 1.6 and 4.0), studies comparable in size to many existing studies are adequate provided the genotyping technology can interrogate more and rarer variants.     

Limbs vs. Jaws: Can They Be Compared?

Current experimental research on mammalian limb muscle structureand function is compared to that on mammalian jaw muscles. Twomajor areas of comparison are stressed: structural and functional.Comparisons of limbs and jaws are made from the point of viewof the impact of recent studies on simple mechanical modelsof limb/jaw muscle function. Limb muscle structure is comparedto jaw muscles at the level of muscle architecture, muscle histochemicaland motor unit properties, and the organization of motor unitsinto neuromuscular compartments. Such comparisons reveal thatalthough limb muscles and jaw muscles might be organized insimilar ways, fundamental differences exist, both in terms ofmuscle structure and the functional conclusions which have beenbased on studies of muscle structure. The comparisons also demonstratethat much recent evidence from structural studies have had littledirect impact on simple models of muscle function but a muchlarger influence on the assumptions of the models. Comparisonsof limb/jaw muscle function from kinematic and EMG studies,indicate that many masticatory strategies are used by differentmammals but the basic problems of posture and locomotion havebeen met with essentially similar solutions, even among diversemammalian groups. The results of such comparisons demonstratethat both limb and jaw muscle function are sufficiently complexthat new or re-vitalized models are needed if the relationshipbetween structure and function are ever to be understood.     

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Background

Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan.

Methods and Findings

Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel.

Conclusion

The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere.     

Reproductive Strategies: How Big Is Your Love?

In swordtails, gene copy number variation is associated with alternative male mating strategies, size and puberty. Though it is unclear how the different aspects are linked mechanistically, the nature of the gene, a melanocortin receptor, suggests avenues for future inquiry.     

Albatrosses Following Fishing Vessels: How Badly Hooked Are They on an Easy Meal?

Fisheries have major impacts on seabirds, both by changing food availability and by causing direct mortality of birds during trawling and longline setting. However, little is known about the nature and the spatial-temporal extent of the interactions between individual birds and vessels. By studying a system in which we had fine-scale data on bird movements and activity, and near real-time information on vessel distribution, we provide new insights on the association of a threatened albatross with fisheries. During early chick-rearing, black-browed albatrosses Thalassarche melanophris from two different colonies (separated by only 75 km) showed significant differences in the degree of association with fisheries, despite being nearly equidistant to the Falklands fishing fleet. Most foraging trips from either colony did not bring tracked individuals close to vessels, and proportionally little time and foraging effort was spent near ships. Nevertheless, a few individuals repeatedly visited fishing vessels, which may indicate they specialise on fisheries-linked food sources and so are potentially more vulnerable to bycatch. The evidence suggests that this population has little reliance on fisheries discards at a critical stage of its nesting cycle, and hence measures to limit fisheries waste on the Patagonian shelf that also reduce vessel attractiveness and the risk of incidental mortality, would be of high overall conservation benefit.     

Cell Penetrating Peptides: How Do They Do It?

Cell penetrating peptides consist of short sequences of amino acids containing a large net positive charge that are able to penetrate almost any cell, carrying with them relatively large cargoes such as proteins, oligonucleotides, and drugs. During the 10 years since their discovery, the question of how they manage to translocate across the membrane has remained unanswered. The main discussion has been centered on whether they follow an energy-independent or an energy-dependent pathway. Recently, we have discovered the possibility of an energy-independent pathway that challenges fundamental concepts associated with protein-membrane interactions (Herce and Garcia, PNAS, 104: 20805 (2007) [1]). It involves the translocation of charged residues across the hydrophobic core of the membrane and the passive diffusion of these highly charged peptides across the membrane through the formation of aqueous toroidal pores. The aim of this review is to discuss the details of the mechanism and interpret some experimental results consistent with this view.