"I Wasn't in My Right Mind": Qualitative Findings on the Impact of Alcohol on Condom Use in Patients Living with HIV/AIDS in Brazil, Thailand, and Zambia (HPTN 063).

PURPOSE: There have been significant biomedical improvements in the treatment and prevention of HIV over the past few decades. However, new transmissions continue to occur. Alcohol use is a known barrier to medication adherence and consistent condom use and therefore may affect treatment as prevention (TasP) efforts. The purpose of this study was to further explore how alcohol is associated with condom use and sexual transmission behavior in three international cities. METHOD: HIV Prevention Trials Network 063 was an observational mixed-methods study of HIV-infected patients currently in care in Rio de Janeiro, Brazil; Chiang Mai, Thailand; and Lusaka, Zambia. Across these three global cities, 80 qualitative interviews were conducted from 2010 to 2012. From these interviews, quotes related to substance use, almost all of which were alcohol, were analyzed using thematic analysis to identify how the use was related to sexual transmission behaviors. RESULTS: Overall, the theme that alcohol impairs cognitive abilities emerged from the data and included the following subthemes: expectancies, impaired decision-making, loss of control, and less concern for others. Themes specific to international settings and risk subgroups were also identified. CONCLUSION: Our analysis identified how alcohol influences sexual transmission behavior in HIV patients in three international settings. These findings may provide direction for content development for future secondary prevention interventions to effectively implement TasP internationally.

Antiretroviral Medication Adherence and Amplified HIV Transmission Risk Among Sexually Active HIV-Infected Individuals in Three Diverse International Settings.

Successful biomedical prevention/treatment-as-prevention (TasP) requires identifying individuals at greatest risk for transmitting HIV, including those with antiretroviral therapy (ART) nonadherence and/or 'amplified HIV transmission risk,' defined as condomless sex with HIV-uninfected/unknown-status partners when infectious (i.e., with detectable viremia or STI diagnosis according to Swiss criteria for infectiousness). This study recruited sexually-active, HIV-infected patients in Brazil, Thailand, and Zambia to examine correlates of ART nonadherence and 'amplified HIV transmission risk'. Lower alcohol use (OR = .71, p < .01) and higher health-related quality of life (OR = 1.10, p < .01) were associated with greater odds of ART adherence over and above region. Of those with viral load data available (in Brazil and Thailand only), 40 % met Swiss criteria for infectiousness, and 29 % had 'amplified HIV transmission risk.' MSM had almost three-fold (OR = 2.89, p < .001) increased odds of 'amplified HIV transmission risk' (vs. heterosexual men) over and above region. TasP efforts should consider psychosocial and contextual needs, particularly among MSM with detectable viremia.

MCAK associates with the tips of polymerizing microtubules.

MCAK is a member of the kinesin-13 family of microtubule (MT)-depolymerizing kinesins. We show that the potent MT depolymerizer MCAK tracks (treadmills) with the tips of polymerizing MTs in living cells. Tip tracking of MCAK is inhibited by phosphorylation and is dependent on the extreme COOH-terminal tail of MCAK. Tip tracking is not essential for MCAK's MT-depolymerizing activity. We propose that tip tracking is a mechanism by which MCAK is preferentially localized to regions of the cell that modulate the plus ends of MTs.

In vitro and in vivo analysis of microtubule-destabilizing kinesins.

Cellular microtubules are rigid in comparison to other cytoskeletal elements (1,2). To facilitate cytoplasmic remodeling and timely responses to cell signaling events, microtubules depolymerize and repolymerize rapidly at their ends (3). These dynamic properties are critically important for many cellular functions, such as spindle assembly, the capture and segregation of chromosomes during cell division and cell motility. Microtubule dynamics are spatially and temporally controlled in the cell by accessory proteins. Molecular motor proteins of the kinesin superfamily that act to destabilize microtubules play important roles in this regulation (4).

Frequency and predictors of estimated HIV transmissions and bacterial STI acquisition among HIV-positive patients in HIV care across three continents.

INTRODUCTION: Successful global treatment as prevention (TasP) requires identifying HIV-positive individuals at high risk for transmitting HIV, and having impact via potential infections averted. This study estimated the frequency and predictors of numbers of HIV transmissions and bacterial sexually transmitted infection (STI) acquisition among sexually active HIV-positive individuals in care from three representative global settings. METHODS: HIV-positive individuals (n=749), including heterosexual men, heterosexual women and men who have sex with men (MSM) in HIV care, were recruited from Chiang Mai (Thailand), Rio De Janeiro (Brazil) and Lusaka (Zambia). Participants were assessed on HIV and STI sexual transmission risk variables, psychosocial characteristics and bacterial STIs at enrolment and quarterly for 12 months (covering 15 months). Estimated numbers of HIV transmissions per person were calculated using reported numbers of partners and sex acts together with estimates of HIV transmissibility, accounting for ART treatment and condom use. RESULTS: An estimated 3.81 (standard error, (SE)=0.63) HIV transmissions occurred for every 100 participants over the 15 months, which decreased over time. The highest rate was 19.50 (SE=1.68) for every 100 MSM in Brazil. In a multivariable model, country×risk group interactions emerged: in Brazil, MSM had 2.85 (95% CI=1.45, 4.25, p<0.0001) more estimated transmissions than heterosexual men and 3.37 (95% CI=2.01, 4.74, p<0.0001) more than heterosexual women over the 15 months. For MSM and heterosexual women, the combined 12-month STI incidence rate for the sample was 22.4% (95% CI=18.1%, 27.3%; incidence deemed negligible in heterosexual men). In the multivariable model, MSM had 12.3 times greater odds (95% CI=4.44, 33.98) of acquiring an STI than women, but this was not significant in Brazil. Higher alcohol use on the Alcohol Use Disorders Identification Test (OR=1.04, 95% CI=1.01, 1.08) was also significantly associated with increased STI incidence. In bivariate models for both HIV transmissions and STI incidence, higher depressive symptoms were significant predictors. CONCLUSIONS: These data help to estimate the potential number of HIV infections transmitted and bacterial STIs acquired over time in patients established in care, a group typically considered at lower transmission risk, and found substantial numbers of estimated HIV transmissions. These findings provide an approach for evaluating the impact (in phase 2 studies) and potentially cost-effectiveness of global TasP efforts.

Intimacy versus isolation: a qualitative study of sexual practices among sexually active HIV-infected patients in HIV care in Brazil, Thailand, and Zambia.

The success of global treatment as prevention (TasP) efforts for individuals living with HIV/AIDS (PLWHA) is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW) and 30 women who have sex with men (WSM) participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM). Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2). There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries indicates that similar intervention content may be effective for a range of settings.

Motor-dependent microtubule disassembly driven by tubulin tyrosination.

In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of alpha-tubulin. The significance of this selective detyrosination of MTs is not understood. In this study, we report that tubulin detyrosination in fibroblasts inhibits MT disassembly. This inhibition is relieved by overexpression of the depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression of MCAK expression prevents disassembly of normal tyrosinated MTs in fibroblasts. Detyrosination of MTs suppresses the activity of MCAK in vitro, apparently as the result of a decreased affinity of the adenosine diphosphate (ADP)-inorganic phosphate- and ADP-bound forms of MCAK for the MT lattice. Detyrosination also impairs MT disassembly in neurons and inhibits the activity of the neuronal depolymerizing motor KIF2A in vitro. These results indicate that MT depolymerizing motors are directly inhibited by the detyrosination of tubulin, resulting in the stabilization of cellular MTs. Detyrosination of transiently stabilized MTs may give rise to persistent subpopulations of disassembly-resistant polymers to sustain subcellular cytoskeletal differentiation.