Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa.

BACKGROUND: Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. METHODS: Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. RESULTS: Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227-661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150-247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16-38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). CONCLUSION: TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.

Empowering Lay-Counsellors with Technology: Masivukeni, a Standardized Multimedia Counselling Support Tool to Deliver ART Counselling.

Lay-counsellors in resource-limited settings convey critical HIV- and ART-information, and face challenges including limited training and variable application of counselling. This study explored lay-counsellors and Department of Health (DoH) perspectives on the utility of a multimedia adherence counselling program. Masivukeni, an mHealth application that provides scaffolding for delivering standardized ART counselling was used in a 3-year randomized control trail at two primary health care clinics in Cape Town, South Africa. In this programmatic and descriptive narrative report, we describe the application; lay-counsellors' response to open-ended questions regarding their experience with using Masivukeni; and perspectives of the City of Cape Town and Western Cape Government DoH, obtained through ongoing engagements and feedback sessions. Counsellors reported Masivukeni empowered them to provide high quality counselling. DoH indicated strong support for a future implementation study assessing feasibility for larger scale roll-out. Masivukeni has potential as a counselling tool in resource-limited settings.

'There's no place like home': perceptions of home-based HIV testing in Lesotho.

HIV testing has the potential to reduce HIV transmission by identifying and counseling individuals with HIV, reducing risk behaviors, linking persons with HIV to care and earlier treatment, and reducing perinatal transmission. In Lesotho, a high HIV prevalence country in which a large proportion of the population has never tested for HIV, home-based testing (HBT) may be an important strategy to increase HIV testing. We identified factors influencing acceptability of HIV prevention strategies among a convenience sample of 200 pregnant or post-partum Basotho women and 30 Basotho men. We first conducted cross-sectional surveys, followed by key informant interviews with all 30 men and focus group discussions with a sub-set of 62 women. In total, 82% of women reported positive perceptions of HBT; women and men viewed HBT as a potential way to increase testing among men and saw the home as a comfortable, supportive environment for testing and counseling couples and families together. Potential barriers to HBT uptake included concerns about confidentiality, privacy, coercion to test, conflict within the family and fear of HIV/AIDS-associated stigma. Participants emphasized community mobilization and education as important elements of HBT.

Association between use of specific drugs and antiretroviral adherence: findings from MACH 14.

To determine the association between individual substances of abuse and antiretroviral adherence, analyses require a large sample assessed using electronic data monitoring (EDM). In this analysis, EDM data from 1,636 participants in 12 US adherence-focused studies were analyzed to determine the associations between recent use of various substances and adherence during the preceding 4 weeks. In bivariate analyses comparing adherence among patients who had used a specific substance to those who had not, adherence was significantly lower among those who had recently used cocaine, other stimulants or heroin but not among those who had used cannabis or alcohol. In multivariate analyses controlling for sociodemographics, amount of alcohol use and recent use of any alcohol, cocaine, other stimulants and heroin each was significantly negatively associated with adherence. The significant associations of cocaine, other stimulants, heroin, and alcohol use with adherence suggest that these are important substances to target with adherence-focused interventions.

Structural barriers to ART adherence in Southern Africa: Challenges and potential ways forward.

Structural barriers to antiretroviral therapy (ART) adherence are economic, institutional, political and cultural factors, that collectively influence the extent to which persons living with HIV follow their medication regimens. We identify three sets of structural barriers to ART adherence that are salient in Southern Africa: poverty-related, institutional, and political and cultural. Examples of poverty-related barriers are competing demands in the context of resource-constrained settings, the lack of transport infrastructure, food insecurity, the role of disability grants and poor social support. Examples of institutional factors are logistical barriers, overburdened health care facilities, limited access to mental health services and difficulties in ensuring adequate counselling. Examples of political and cultural barriers are controversies in the provision of treatment for AIDS, migration, traditional beliefs about HIV and AIDS, poor health literacy and gender inequalities. In forging a way forward, we identify ways in which individuals, communities and health care systems may overcome some of these structural barriers. Finally, we make recommendations for further research on structural barriers to ART adherence. In all likelihood, enhancing adherence to ART requires the efforts of a variety of disciplines, including public health, psychology, anthropology, sociology and medicine.

Is 'bareback' a useful construct in primary HIV-prevention? Definitions, identity and research.

The terms bareback and bareback identity are increasingly being used in academic discourse on HIV/AIDS without clear operationalization. Using in-depth, face-to-face interviews with an ethnically diverse sample of 120 HIV-infected and -uninfected men, mainly gay-identifying and recruited online in New York City, this study explored respondents' definitions of bareback sex, the role that intentionality and risk played in those definitions, and whether respondents identified as 'barebackers'. Results showed overall agreement with a basic definition of bareback sex as condomless anal intercourse, but considerable variation on other elements. Any identification as barebacker appeared too loose to be of use from a public health prevention perspective. To help focus HIV-prevention efforts, we propose a re-conceptualization that contextualises risky condomless anal intercourse and distinguishes between behaviours that are intentional and may result in HIV-primary transmission from those that are not.

Screening for depressive symptoms in an online sample of men who have sex with men.

Depression is a debilitating disorder and relatively high rates have been reported in studies of men who have sex with men (MSM). This study was undertaken to assess the utility of screening for, and characteristics associated with, depressive symptoms in an online survey of MSM. In 2003-2004, an online cross-sectional study was conducted among 2,964 MSM from the US and Canada. Using the two-item Patient Health Questionnaire (PHQ-2), 18% of the study participants screened positive for depressive symptoms within the past three months. Characteristics associated with a positive PHQ-2 screen for depressive symptoms in multivariate analysis included: having less than a high school or college degree; being single (not having a primary male partner) or being married to a woman; being HIV-positive; and not having recent sex. Additionally, among men who screened positive on the PHQ-2, predictors of not having treatment from a mental health provider in the past year were: low education; being black/African American/Canadian or Hispanic; and having no primary care provider. The Internet is a viable medium to reach and screen men at-risk for depression. Future work is needed for online outreach and connection to offline assessment as well as intervention.

Characteristics of bisexually active men in the Seropositive Urban Mens' Study (SUMS).

Characteristics of bisexually-active men were compared with those of their homosexually-active counterparts in a study of HIV-seropositive men who have sex with men (MSM). Men who had had sex with women in the prior year were younger and more likely to be African American than those reporting sex only with men. They reported higher levels of internalised homophobia and less participation in the gay community. They tended to be recruited through friend referral rather than public sex environments or AIDS service organisations. However, they did not seek sex partners from different venues than other participants. Implications for HIV transmission risk-reduction interventions for this population are discussed.

Adherence to antiretroviral therapy in a context of universal access, in Rio de Janeiro, Brazil.

Adherence is integral to improving and maintaining the health and quality of life of people living with HIV. Two-hundred HIV-positive adults recruited from teaching hospitals and non-governmental organizations (NGOs) in Rio de Janeiro City were assessed on socio-demographic factors, adherence to antiretroviral therapy (ART) and psychosocial factors hypothesized to be associated with ART. Predictors of non-adherence were analyzed using bivariate and multivariate analyses. Self-reported medication adherence was high (82% had adherence >90%). Non-adherence was associated with personal factors (i.e. sexual orientation, self-efficacy), physical factors (i.e. loss of appetite) and interpersonal factors (i.e. doctor-patient relationship). Adherence in Brazil is as good, if not better, than that seen in the US and western Europe, which is noteworthy since the sample was derived predominantly from public healthcare settings. It is possible that the connection to NGOs in Rio de Janeiro City played a helpful role in achieving high levels of adherence in this sample of people living with HIV and AIDS. Recommendations, based on study findings, include enhancing and sustaining supportive services for NGOs, promoting patient self-efficacy and behavioral skills for adherence, increasing social network support and having healthcare providers directly address patients' medication beliefs, attitudes and experience with side effects.

Substance use and high-risk sex among men who have sex with men: a national online study in the USA.

This paper describes drug and sexual risk behaviors during a six-month period in 2001 of 2,916 gay and bisexual men who were recruited online. Bivariate and multivariate analyses examined correlates of unprotected anal intercourse (UAI). Drug and alcohol use were also examined by US region. UAI was associated with using alcohol or drugs, including poppers, crystal methamphetamine, cocaine, marijuana and Viagra before or during sex. Meeting sex partners both online and offline and having multiple sex partners were also predictive of UAI. Significant regional differences were seen in the prevalence of drug use and alcohol use. Findings are discussed in relation to the need to integrate messages about the relationship between drug use and sexual behavior into HIV prevention programs.

Intricacies and inter-relationships between HIV disclosure and HAART: a qualitative study.

This study aimed to understand whether and how highly active antiretroviral treatment (HAART) affects views and patterns of disclosure and how disclosure interacts with treatment decisions. One hundred and fifty-two HIV-positive adults (52 MSM, 56 women and 44 IDU men) from four US cities participated in two to three-hour, semi-structured interviews in 1998-99. Results indicate that HAART interacts with and shapes HIV disclosure issues in several ways. Medications may 'out' people living with HIV. Thus, in different settings (e.g. work, prisons, drug rehabs and public situations), some try to hide medications or modify dosing schedules, which can contribute to non-adherence, and affect sexual behaviours. Disclosure of HIV and/or HAART may also result in antagonism from others who hold negative attitudes and beliefs about HAART, potentially impeding adherence. Observable side effects of medications can also 'out' individuals. Conversely, medications may improve appearance, delaying or impeding disclosure. Some wait until they are on HAART and look 'well' before disclosing; some who look healthy as a result of medication deny being HIV-positive. Alternatively, HIV disclosure can lead to support that facilitates initiation of, and adherence to, treatment. HIV disclosure and adherence can shape one another in critical ways. Yet these interactions have been under-studied and need to be further examined. Interventions and studies concerning each of these domains have generally been separate, but need to be integrated, and the importance of relationships between these two areas needs to be recognized.

Levels and correlates of psychological distress in male couples of mixed HIV status.

Few studies have analyzed the impact of HIV infection on dyadic functioning and on the distress levels of each partner, independently, in HIV-serodiscordant relationships, particularly in same-sex dyads. The main purpose of this study was to assess levels of psychological distress in the HIV-positive and HIV-negative members of HIV-discordant male couples and to explore possible couple-related factors associated with distress. This was done within a systems theory framework. Levels of distress among the men were in the mild to moderate range, according to general population norms. Factors associated with distress in the men included dyadic satisfaction, sexual satisfaction, avoidance and self-blame coping style, and support from one's partner. Results suggest the need for 'couple-focused' clinical interventions for HIV-discordant couples.

Childhood sexual abuse and sexual transmission risk behaviour among HIV-positive men who have sex with men.

Previous studies have indicated an association between childhood sexual abuse (CSA) and adult sexual risk behaviour among women and among men who have sex with men (MSM). However, no studies to date have tested the hypothesis that a history of CSA predicts sexual behaviour carrying risk of transmission of HIV to others, i.e. in a known HIV-positive cohort. The present study tested this hypothesis among a sample of 456 HIV-positive MSM recruited from community venues in New York and San Francisco. CSA history was found to be significantly associated with past (in the last 90 days) unprotected anal sex acts, both insertive (33% versus 20%, p < 0.05) and receptive (43% versus 27%, p < 0.02), with partners of HIV-negative or unknown serostatus. Further, several potential mediators of this effect were tested, and three found to be predicted by CSA history. Each of these potential mediators was associated with sexual risk behaviour, but differentially: anxiety and hostility were significantly associated with insertive acts, while anxiety, hostility and suicidality were associated with receptive acts. Mediation analyses supported the hypothesis that these factors significantly (albeit partially) accounted for the association of CSA with receptive anal intercourse. Nonsignificant mediation effects were found for insertive sex, suggesting the operation of unmeasured mediating variables. These results highlight the importance of mental health services for individuals who have been sexually abused, both for personal and for public health benefit, and also indicate a need for further research into mediators of CSA effects on transmission-related behaviour.

Characteristics of HIV antiretroviral treatments, access and adherence in an ethnically diverse sample of men who have sex with men.

Data regarding HIV antiretroviral treatment regimens, access to treatment and medical care, and adherence to medications were collected as part of the Seropositive Urban Men's Study, a formative study of HIV-positive men who have sex with men. Participants (N = 456) were recruited from AIDS service organizations, mainstream gay venues and public/commercial sex environments. The sample was 94% gay or bisexually-identified; 29% were African American, 24% Latino and 30% white. The majority (71%) indicated being on antiretroviral treatment, and most were taking a protease inhibitor/nucleoside reverse transcriptase inhibitor combination. African American men in New York City were less likely to be on treatment. Among those on treatment (n = 322), 51% reported at least one day in which they had missed a dose of their medication and the mean number of days in which a dose was missed (in the past 30 days) was 1.72. Multivariate analyses indicated that avoidant coping, frequency of drinking alcohol and difficulty in communicating with sex partners about HIV were related to days of missed doses, suggesting the need or desire to escape from the reality of life with HIV as a potential explanation for poor adherence.

Correlates of adherence to combination antiretroviral therapy among members of HIV-positive mixed status couples.

This exploratory study assessed medication adherence and its correlates in HIV-positive members of HIV mixed status couples. Forty couples were interviewed; the HIV-positive participants consisted of 19 gay men, 14 heterosexual men and seven heterosexual women. Mean self-reported adherence (over the past three days) for the whole sample was 95%; the mean adherence rate for gay men (99%) was significantly higher (p < 0.05) than that of heterosexual men (94%) and heterosexual women (87%) based on a ranked transformation of the adherence score. In analyses involving measures rated by the HIV-positive partner, higher adherence was associated with more years of education, greater perceived treatment efficacy, stronger belief that combination therapy is a significant advancement in treatment, and greater knowledge of HIV treatments and consequences of poor adherence. Higher adherence was associated with the HIV-negative partner attributing less risk to unprotected anal/vaginal sex within the couple, while lower adherence was associated with a greater likelihood that the couple engaged in unprotected anal/vaginal sex in the last two months. A larger sample is needed to substantiate these findings.

Prevalence of extradyadic sex in male couples of mixed HIV status and its relationship to psychological distress and relationship quality.

This study assessed the prevalence of extradyadic sex and the relationship between such activity and psychological distress and relationship quality in male couples of mixed HIV serostatus. Sixty-three couples were interviewed and had sufficient data for inclusion in all analyses. With regard to sexual activity during the year prior to being interviewed, 19 (30%) couples were monogamous, 18 (29%) described themselves as "open," 13 (21%) kept extradyadic sex a secret from their partners, and in 13 couples there was only partial knowledge of extradyadic sex. Though not statistically significant, monogamous and open couples consistently scored lower numerically on measures of psychological distress and higher on measures of relationship quality, compared to "partial knowledge" and "secretive" couples. When pooled, monogamous and open couples scored significantly higher on measures of dyadic consensus, affectional expression, dyadic satisfaction, and sexual satisfaction compared to the combined subgroup of partial knowledge and secretive couples.

HIV prevention in the era of HAART: implications for providers.

This article reviews the medical literature regarding the association between reduced HIV viremia caused by use of HAART and the risk of HIV transmission, finding that there is a correlation but that it is not absolute. It then examines the behavioral literature, which indicates that there is evidence, though far from conclusive, that, for some, increased sexual risk taking may be related to attitudes and beliefs about combination therapy. The article also considers the message about HIV prevention being presented by public health programs and ways in which health care providers can outline changing circumstances and enable the patient to make informed choices in "gray areas."

Difficulties in interpersonal relationships associated with personality disorders and axis I disorders: a community-based longitudinal investigation.

A longitudinal study was conducted to investigate the association between Axis I and Axis II psychiatric disorders, interpersonal relationships, and global functioning among men in the community. Structured clinical interviews assessing Axis I and Axis II psychiatric disorders, global assessments of functioning, and questionnaires assessing social support, social conflict, and loneliness were administered to a community sample of 95 HIV+ and 45 HIV- men. The questionnaires were readministered 1 year later. Results indicated that (a) Personality disorders (PDs) and unipolar depressive disorders were associated with loneliness, social conflict, and low levels of social support after HIV status was controlled statistically; (b) PDs were associated with interpersonal and global impairment after HIV status and co-occurring Axis I disorders were controlled statistically; (c) Axis I disorders were associated with global impairment, but were not associated with interpersonal difficulties after HIV status and PDs were controlled statistically; (d) PDs, but not Axis I disorders, predicted increases in social conflict and global impairment after HIV status was controlled statistically; (e) PDs continued to predict increases in global impairment after both Axis I disorders and HIV status were controlled statistically; and (f) HIV+ men reported more loneliness, less social support, and had a higher prevalence of substance use disorders than HIV- men. The present findings are of particular interest because they suggest that PDs are associated with loneliness, social conflict, and a lack of social support among men in the community, whether or not Axis I disorders are present.

Frequency and clinical determinants of dementia after ischemic stroke.

OBJECTIVE: To investigate the frequency and clinical determinants of dementia after ischemic stroke. METHODS: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 +/- 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. RESULTS: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). CONCLUSIONS: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors' cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke.