Targeted ethnography as a critical step to inform cultural adaptations of HIV prevention interventions for adults with severe mental illness.

As in other countries worldwide, adults with severe mental illness (SMI) in Brazil are disproportionately infected with HIV relative to the general population. Brazilian psychiatric facilities lack tested HIV prevention interventions. To adapt existing interventions, developed only in the US, we conducted targeted ethnography with adults with SMI and staff from two psychiatric institutions in Brazil.

Arginine methylation of the HIV-1 nucleocapsid protein results in its diminished function.

Objective: The HIV-1 nucleocapsid protein (NC) is involved in transfer RNA3 annealing to the primer binding site of viral genomic RNA by means of two basic regions that are similar to the N-terminal portion of the arginine-rich motif (ARM) of Tat. As Tat is known to be asymmetrically arginine dimethylated by protein arginine methyltransferase 6 (PRMT6) in its ARM, we investigated whether NC could also act as a substrate for this enzyme.

Methods: Arginine methylation of NC was demonstrated in vitro and in vivo, and sites of methylation were determined by mutational analysis.

Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations.

Objectives: To determine the underlying biochemical mechanisms responsible for the diminished viral replicative capacity associated with K65R/M184V-containing viruses.

Methods: We studied the efficiency of (-)ssDNA synthesis by recombinant wild-type and mutated HIV-1 reverse transcriptases in cell-free assays. In addition, we determined susceptibility levels to nucleoside analog reverse transcriptase inhibitors (NRTIs) both in cell-free and cell culture assays.

High rates of forward transmission events after acute/early HIV-1 infection.

Background: A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)-transmission dynamics in Quebec.

Methods: HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998-2005; n=215) and the provincial genotyping program (2001-2005; n=481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n=593) and infections from untreated (n=135) and treated (n=660) chronically infected (CI) potential transmitter populations (2001-2005).

A randomized controlled trial of goal choice interventions for alcohol use disorders among men who have sex with men.

This study tested the efficacy of behavioral treatments for alcohol use disorders (AUD) among men who have sex with men (MSM) and who are at risk for HIV transmission. HIV-negative MSM with current AUD (N = 198) were recruited, offered treatment focused on reducing drinking and HIV risk, and followed during treatment and 12 months posttreatment. Participants (n = 89) accepted treatment and were randomized to either 4 sessions of motivational interviewing (MI) or 12 sessions of combined MI and coping skills training (MI + CBT).

Impact of the 16th International Conference on AIDS: can these conferences lead to policy change?

This Commentary reflects on the success of the XVI International Conference on AIDS, that was held in Toronto between August 13-18, 2006. Not only was the Conference judged to have been a scientific success, it will probably also be recognized over time as having had important political impact. It is vital that scientists and policy-makers continue to be able to interact at these meetings as part of global efforts to combat the HIV epidemic.

New pandemics: HIV and AIDS, HCV and chronic hepatitis, influenza virus and flu.

New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year.

Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat Interactions with both cyclin T1 and the Tat transactivation region.

Arginine methylation has been shown to regulate signal transduction, protein subcellular localization, gene transcription, and protein-protein interactions that ultimately alter gene expression. Although the role of cellular protein arginine methyltransferases (PRMT) in viral gene expression is largely unknown, we recently showed that the Tat protein of human immunodeficiency virus type 1 (HIV-1) is a substrate for one such enzyme, termed PRMT6. However, the mechanism by which arginine methylation impairs the transactivation potential of Tat and the sites of arginine methylation within Tat remain obscure.

A model for adapting evidence-based behavioral interventions to a new culture: HIV prevention for psychiatric patients in Rio de Janeiro, Brazil.

As in other countries worldwide, adults with severe mental illness in Brazil have elevated rates of HIV infection relative to the general population. However, no HIV prevention interventions have been tested for efficacy with psychiatric patients in Brazil. We conducted participatory research with local providers, community leaders, patient advocates, and patients using an intervention adaptation process designed to balance fidelity to efficacious interventions developed elsewhere with fit to a new context and culture.

A double-blind study of citalopram versus placebo in the treatment of compulsive sexual behaviors in gay and bisexual men.

Objective: Compulsive sexual behavior (CSB) is a condition characterized by loss of control over sexual behavior and repeated negative consequences, including unsafe sex. Selective serotonin reuptake inhibitors have been found to reduce CSB symptomatology in open-label trials. The objective of this study was to conduct a preliminary double-blind, placebo-controlled evaluation of the efficacy, acceptability, and tolerability of citalopram in the treatment of CSB.

Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIVmac239.

Background: The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIVmac239) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation, expression, and the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a series of deletions in the SIVmac239 leader sequence in order to determine the involvement of this region in both the packaging and dimerization of viral genomic RNA. We also assessed the impact of these deletions upon viral infectiousness, replication kinetics and gene expression in cell lines and monkey peripheral blood mononuclear cells (PBMC).

PRMT6 diminishes HIV-1 Rev binding to and export of viral RNA.

Background: The HIV-1 Rev protein mediates nuclear export of unspliced and partially spliced viral RNA through interaction with the Rev response element (RRE) by means of an arginine rich motif that is similar to the one found in Tat. Since Tat is known to be asymmetrically arginine dimethylated by protein arginine methyltransferase 6 (PRMT6) in its arginine rich motif, we investigated whether the Rev protein could act as a substrate for this enzyme.

Results: Here, we report the methylation of Rev due to a single arginine dimethylation in the N-terminal portion of its arginine rich motif and the association of Rev with PRMT6 in vivo.

Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors.

Human immunodeficiency virus type 2 (HIV-2) contains numerous natural polymorphisms in its protease (PR) gene that are implicated in drug resistance in the case of HIV-1. This study evaluated emergent PR resistance in HIV-2. Three HIV-2 isolates were selected for resistance to amprenavir (APV), nelfinavir (NFV), indinavir (IDV), and tipranavir (TPV) in cell culture.

Criteria for drugs used in pre-exposure prophylaxis trials against HIV infection.

The authors formulate criteria for an optimal pre-exposure prophylaxis drug candidate, and evaluate existing antiviral drug classes for their suitability.

Training South African mental health care providers to talk about sex in the era of AIDS.

Objective: Mental health care providers in South Africa often lack the skills to conduct effective prevention activities in psychiatric settings. This article describes the development and evaluation of an HIV education program for mental health care providers at three psychiatric institutions in South Africa.

Methods: The research team worked with a core group of 16 mental health care providers to assess HIV training needs and to develop a training intervention focused on identified issues.

High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens.

We analyzed the reverse transcriptase genotypes of human immunodeficiency virus type 1 subtype C viruses isolated from 23 patients in Botswana treated with didanosine-based regimens. The K65R mutation was selected either alone or together with the Q151M, S68G, or F116Y substitution in viruses from seven such individuals. The results of in vitro passage experiments were consistent with an apparent increased propensity of subtype C viruses to develop the K65R substitution.

HIV resistance to antiviral drugs: public health implications.

The widespread occurrence of HIV strains resistant to antiviral drugs has given rise to a number of important concerns distinct from the obvious question of the relationship between drug resistance and treatment failure. A major issue is the extent to which drug-resistant viruses may be transmitted in primary infection via sexual or intravenous routes and how this relates to the relative fitness of such strains. It is also important to understand the potential role of effective antiviral therapy in the decrease of viral burden in both blood and sexual secretions, and the extent to which this may be compromised in individuals harboring resistant viruses.

A low-cost, sustainable intervention for drinking reduction in the HIV primary care setting.

Excess drinking poses multiple substantial health risks to HIV-infected individuals. However, no published intervention studies have focused on drinking reduction as the main outcome in HIV primary care patients. An intervention in this setting must place minimal demands on pressured staff and resources.

HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture.

Background: Genotypic diversity among HIV-1 subtypes and circulating recombinant forms (CRF) may lead to distinct pathways to drug resistance. This study evaluated subtype-related differences in the development of resistance in culture to tenofovir.

Methods: Genotyping determined nucleotide diversity among subtypes.

Is HIV drug resistance a limiting factor in the development of anti-HIV NNRTI and NRTI-based vaginal microbicide strategies?

Antiviral drugs that act at specific sites within the HIV life cycle have important rationale for development as anti-HIV microbicides. However, to be effective, such drugs must act by directly interfering with viral enzymatic function and eliminate the ability of HIV to mediate infection. Compounds that are developed as microbicides must have high potency, and should ideally not be well absorbed from the vaginal cavity in order to minimize any potential problems of drug resistance.