Directly Administered Antiretroviral Therapy for HIV-Infected Individuals in Opioid Treatment Programs: Results from a Randomized Clinical Trial

Background

Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.

Methods

HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.

Results

We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log₁₀ HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.

Conclusions

In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.

Trial Registration

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Interleukin-6 Receptor Blockade Selectively Reduces IL-21 Production by CD4 T Cells and IgG4 Autoantibodies in Rheumatoid Arthritis

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Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists

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Climate change and community disassembly: impacts of warming on tropical and temperate montane community structure

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Mhc supertypes confer both qualitative and quantitative resistance to avian malaria infections in a wild bird population

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Incorporating ecological principles into statistical models for the prediction of species’ distribution and abundance

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Spatial determinants of infection risk in a multi‐species avian malaria system

Spatially‐variable processes can be an important element of host–parasite interactions, but their longer term demographic and evolutionary effects depend on the magnitude of variation in space, the scale at which variation occurs and the degree to which such processes are temporally stable. Here, we use multiple years of data from a study of two closely related tit species (Paridae), infected with two congeneric species of avian malaria (Plasmodium), to evaluate the roles of extrinsic and intrinsic factors in driving spatial heterogeneity in infection risk, and to address questions of scale and temporal stability in these vector‐driven host–parasite interactions. We show that the two malaria parasite species exhibit markedly different spatial epidemiology: P. relictum infections are effectively randomly distributed in space, with no temporal consistency, whereas P. circumflexum infections exhibit pronounced spatial structuring that is stable over the six years of this study and similar in both host species. We show that both conspecific and heterospecific host density contribute to elevated infection risk, but that the main determinants of elevated risk of P. circumflexum infection risk are habitat features probably associated with vector distribution and abundance. We discuss the implications of these findings, both for our understanding of the epidemiology of malaria in the wild, but also in terms of the longer‐term evolutionary and demographic consequences that spatially variable parasite‐mediated selection may have on host populations.     

Isolation and Identification of Volatile Chemicals Formed in Aqueous l-Cysteine Solution with a UV Light

Thirty-six volatile compounds were positively identified in the dichloromethane extract of an aqueous solution of l-cysteine that was irradiated with UV light at 253.7 nm for 24 hr. The irradiated solution was colorless but has a cooked meat-like flavor. The compounds identified were thiophenes, pyrazines, thiazoles, thiazolines, thiazolidines, and polymethylene sulfides. 2-Methylthiazole was found in the largest quantity, approximately 40% of the extract. Proposed photochemical reactions of cysteine included Strecker degradation, isomerization, dimerization, and homolytic fission of C-C, C-S, or S-H bonding.     

Discontinuous Molecular Dynamics (DMD) Study of Heteropolymer Collapse in an Explicit Solvent

In this study, we employ the discontinuous molecular dynamics simulation method to investigate the collapse properties of a single heteropolymer chain in an explicit solvent. Solvent density ρ, fraction of hydrophobic monomers n _H (defined as the ratio of the number of hydrophobic monomers to the total number of monomers) and a hydrophobicity parameter λ (which controls the energy mismatch between the monomers and solvent particles) were systematically varied to examine their role in polymer collapse. The average static structure factor of the polymer was used to find the so-called θ-point characterizing the state of an ideal chain. Phase diagrams of ρ versus λ for the coil–globule transition were mapped out for different values of n _H. Increasing the fraction of hydrophobic monomers n _H, solvent density ρ, and hydrophobicity parameter λ were all shown to aid in stabilizing the globule phase. In an effort to explore scaling behaviour of the coil–globule phase diagram as a function of n _H, and to investigate whether the phase boundaries for different n _H collapsed on to one universal curve, we rescaled λ by n _H ^δ λ; we determined δ = 1.72, in contrast to mean-field predictions of δ = 2.0.     

Observations on the specific associations found between scyphomedusae and commensal fish and invertebrates in the Philippines

Our observations on scyphomedusae from selected Philippine embayments identified specific animals commensal with five species of rhizostome scyphomedusae, Acromitoides purpurus, Mastigias sp., Phyllorhiza punctata, Rhopilema hispidum and Versuriga anadyomene. Acromitoides purpurus medusae harbor the crab Charybdis feriata, the carangid fish Alepes djedaba and the poecilostomatoid copepod Paramacrochiron sp. The carangid A. djedaba was an associate of the blue morph of A. purpurus and Rhopilema hispidum in Panguil Bay. A black-pigmented Alepes sp. was found associated with burgundy A. purpurus medusae in Carigara Bay. Charybdis feriata juveniles are common commensals of all morphs of A. purpurus, R. hispidum and P. punctata medusae. Only the zooxanthelate Mastigias sp. lacked animal symbionts. We invoke the “meeting-point hypothesis” and the general theory of fish aggregation to floating structures to explain fish symbiosis with their medusan hosts. The invertebrate-medusa associations are attributed to feeding behaviors and predator avoidance by resident commensals. This study provides record of the poorly studied scyphozoan species and their association with animals in Philippine waters. Finally, we discuss the potential reasons why the golden spotted jellyfish, Mastigias sp., appears to lack animal commensals.