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.

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.

Depression, distress, lymphocyte subsets, and human immunodeficiency virus symptoms on two occasions in HIV-positive homosexual men.

We evaluated the extent to which depressive disorders, psychiatric distress, and psychosocial stressors are related to three measures of human immunodeficiency virus (HIV) illness, both cross-sectionally and during a 6-month period, in a community sample of 124 HIV-positive homosexual men. The dependent variables are immune status measured by CD4 and CD8 cell subsets, number of signs and symptoms commonly associated with HIV infection, and a cumulative index of HIV illness stage. We chose to focus on CD4 cell count because it is the immune marker most closely linked to the clinical consequences of HIV infection. We found no relationships between the independent variables and immune status or illness stage. The HIV-positive men who were depressed or distressed or who reported more life stressors had no greater immunosuppression or more advanced illness stage than did the others, either concurrently or across occasions. We did find a suggestive pattern of association between depressive disorders, distress, and stressors and the number of HIV-related symptoms, which warrants further study.

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. II. Standardized clinical assessment of current and lifetime psychopathology.

Despite numerous reports of the psychiatric consequences of human immunodeficiency virus infection, few reports describe systematic diagnostic assessments of people with human immunodeficiency virus infection. We studied the results of standardized clinical assessments of current and lifetime psychopathology in a large group of homosexual men whose serologic status was known. Results indicated low rates of current mental disorders but very high rates of lifetime major depression and alcohol and other psychoactive substance abuse and dependence disorders. Measures of severity of psychopathology and functioning also indicated, on the whole, good current functioning. No significant relationship was found between stage of medical illness or immune status and any measure of psychiatric disturbance.

Personality disorders predict onset of Axis I disorders and impaired functioning among homosexual men with and at risk of HIV infection.

BACKGROUND: A longitudinal study was conducted to investigate whether personality disorders (PDs) increase risk for the development of future Axis I disorders and serious functional impairment among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative homosexual men. METHOD: Baseline assessments of PDs, Axis I disorders and symptoms, and Global Assessments of Functioning were conducted with a community sample of 107 (66 HIV-positive and 41 HIV-negative) homosexual men participating in a longitudinal study with semiannual interviews over 3 years. RESULTS: Logistic regression analysis indicated that PDs predicted onset of subsequent Axis I disorders after controlling for both HIV status and lifetime Axis I history (adjusted odds ratio, 4.31; P=.01; 95% confidence interval, 1.39 to 13.32). Of the 21 participants with PDs, 16 (76%) were subsequently diagnosed with Axis I disorders on at least one occasion. By contrast, only 36 (42%) of the 86 participants without PDs were subsequently diagnosed with Axis I disorders. Further, 33% of the participants with PDs, in comparison with only 8% of those without PDs, were assigned Global Assessments of Functioning scores of 50 or lower, indicating serious impairment during the postbaseline study period (adjusted odds ratio, 5.70; P<.005; 95% confidence interval, 1.66 to 19.53). CONCLUSION: Personality disorders may contribute to increased risk for onset of Axis I disorders and serious impairment among homosexual men regardless of HIV serologic status.

Psychopathology in male and female HIV-positive and negative injecting drug users: longitudinal course over 3 years.

OBJECTIVE: To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. DESIGN: As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. RESULTS: At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46-51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree to HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. CONCLUSIONS: High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.

Maintenance of hope in HIV-spectrum homosexual men.

The struggle to maintain hope has been described as a central theme faced by clinicians who work with HIV-spectrum people. The authors investigated psychiatric and psychosocial variables thought to be related to level of hope in a community sample of 208 HIV-positive and HIV-negative homosexual men, with the goal of identifying possible risk and protective factors in the progression of HIV infection. Overall, they found high levels of hope and low levels of current syndromal disorder or depressive symptoms. While the sample was a selected group of successful and well-educated homosexual men, it nevertheless remains noteworthy that they were able to preserve a sense of faith in their future despite HIV infection.

Bereavement reactions among homosexual men experiencing multiple losses in the AIDS epidemic.

OBJECTIVE: The authors examined whether deaths of lovers and close friends from AIDS increased the frequency of depressive symptoms and depressive disorder in a group of homosexual men. METHOD: Two hundred seven volunteer male homosexual subjects were interviewed in New York City in 1988 and 1989. Depressive symptoms were measured with the Hamilton Rating Scale for Depression, administered by a clinician, and two self-report symptom checklists. Subjects were evaluated for major depression with the Structured Clinical Interview for DSM-III-R. Each subject also reported the number of lovers and close friends who had died of AIDS 1) since the beginning of the epidemic in 1981 and 2) in the 6 months preceding the interview. RESULTS: Neither the overall level of depressive symptoms, the presence of specific symptom clusters, nor the presence of a diagnosed depressive disorder was related to the number of AIDS deaths a subject reported in either time frame. In contrast, bereavement reactions specific to loss, namely, preoccupation with and searching for the deceased, were more common in subjects with greater numbers of losses. The findings for depressive symptoms and major depression are not readily explained by measurement artifact, overrepresentation of asymptomatic subjects among study volunteers, habituation effects, numbness, or shallowness of attachments in the subjects. CONCLUSIONS: Changes in normative expectations regarding AIDS deaths and mobilization against AIDS within the gay community may account for the lack of association between the number of losses resulting from AIDS and the presence of depressive symptoms and depressive disorder.

Axis I psychiatric symptoms associated with HIV infection and personality disorder.

OBJECTIVE: The prevalences of personality disorders among HIV-positive and HIV-negative homosexual men were compared, and the presence of personality disorders was related to axis I psychiatric disorders, psychiatric distress, and impaired functioning. METHOD: The subjects were 162 homosexual men who either were HIV seronegative (N = 52) or were seropositive and had absent to moderate physical symptoms (N = 110). Lifetime and current histories of DSM-III-R axis I disorders, current diagnoses of DSM-III-R personality disorders, and levels of anxiety, depression, hopelessness, and adaptive functioning were assessed. RESULTS: In both the seropositive and seronegative groups, 19% of the study participants were diagnosed with personality disorders. The seropositive participants with personality disorders reported higher levels of psychiatric symptoms and poorer functioning than all participants without personality disorders, and they were over six times as likely as the seronegative participants without personality disorders to have current axis I disorders. CONCLUSIONS: These findings indicate that HIV infection and personality disorders may interactively increase the likelihood of clinically significant psychiatric symptoms.

Psychopathology in male and female intravenous drug users with and without HIV infection.

OBJECTIVE: The authors report on results of systematic clinical assessment of psychopathology among HIV-positive and HIV-negative intravenous drug users. METHOD: As part of a multidisciplinary baseline assessment, 147 male (85 HIV-positive and 62 HIV-negative) and 76 female (39 HIV-positive and 37 HIV-negative) intravenous drug users were evaluated with the Structural Clinical Interview for DSM-III-R and measures of psychiatric symptom severity, global functioning, and stress. RESULTS: Prevalence of a diagnosis of current depression (26%) and severity of depressive and anxiety symptoms in both HIV-positive and HIV-negative subjects were greater than in the general community, but not greater than in other studies of intravenous drug users. HIV-positive men had a higher prevalence of depressive disorders than HIV-negative men (33% and 16%, respectively), although this pattern was not found among women (26% and 30%). Diagnosis of depressive disorders and severity of depressive and anxiety symptoms were associated with a symptom-based measure of HIV illness stage, but not with indices of immune functioning (CD4+ cell count and CD4+ cell percent). CONCLUSIONS: Despite selective associations between HIV illness variables and depression, high rates of depression across HIV status in this cohort suggest that intravenous drug use and associated factors are more salient than HIV illness factors in understanding psychopathology in this population.

Stability of mood despite HIV illness progression in a group of homosexual men.

OBJECTIVE: The authors investigated the association between mood status and progression of HIV illness. METHOD: In a research clinic at a university medical center, 112 HIV-positive and 52 HIV-negative homosexual men were enrolled in a 4-year prospective study with semi-annual assessments. The main study measures were psychiatric diagnoses according to the Structured Clinical Interview for DSM-III-R; level of functioning and psychiatric symptoms according to the Global Assessment of Functioning Scale (axis V, DSM-III-R), the Hamilton depression and anxiety scales, the Brief Symptom Inventory, and the Beck Hopelessness Scale; stage of HIV illness; and CD4 cell count. RESULTS: Among the HIV-positive men, there was no increase in rates of syndromal depression and anxiety over the 4 years despite substantial HIV illness progression. On all occasions, mean psychopathology symptom ratings were within the normal or not depressed range. However, compared to the HIV-negative men, the HIV-positive men had slightly more anxiety and somatic depressive symptoms throughout. The only measure that showed an increase in distress over time was orientation to the future; among the HIV-positive men, hopes for the future waned across assessments. Attrition in the group was largely attributable to the loss of men with lower CD4 cell counts and more advanced HIV illness. However, study dropouts did not differ on any psychiatric measure from subjects who remained during the first 3 years. CONCLUSIONS: In this group no significant increase in syndromal or symptomatic depression or anxiety over nine semiannual assessments was found, despite substantial HIV illness progression and some deaths. Psychopathology did not predict dropout or death.

Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort.

We determined the frequency of dementia in a cohort of 251 patients aged greater than or equal to 60 years hospitalized with acute ischemic stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa = 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 (p less than 0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 (p less than 0.001) with significant age and race effects. We conclude that ischemic stroke significantly increases the risk of dementia, with independent contributions by age, education, and race.

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.

Stability and change in personality disorder symptomatology: findings from a longitudinal study of HIV+ and HIV- men.

A longitudinal study was conducted to investigate the stability of personality disorders (PDs) over a 2-year interval, as well as the association between change in PD symptomatology and change in psychological distress. Structured clinical interviews and questionnaires assessing PDs and psychological distress were administered to a community sample of 118 gay men (80 HIV seropositive men and 38 HIV seronegative men) at a baseline session and readministered 2 years later. Results indicated that PD symptom levels tended to be moderately stable, that PD diagnoses had low stability and that changes in PD symptom levels were associated with changing levels of psychological distress but not with progression of HIV infection.

Disease severity, physical limitations and depression in HIV-infected men.

Previous research has failed to identify a consistent relationship between HIV disease severity and depression. However, HIV/AIDS can lead to substantial physical limitations in those with advanced disease, which may influence mood. This study examined the extent to which HIV disease severity and physical limitations were associated with depressive symptoms in 49 HIV-infected men at the final stages of a 5-year prospective study. No differences were found in depression or quality of life among men who were asymptomatic, symptomatic, or diagnosed with AIDS. Forty-three percent of subjects reported substantial physical limitations, which were associated with higher depression scores and poorer quality of life. Degree of physical limitation predicted depression concurrently as well as depression 6 months later, after controlling for disease stage, physical symptoms, and CD4 cell counts. Findings suggest that physical limitations are more important than laboratory markers of disease progression in understanding psychological adjustment to illness in HIV-infected men.

"Extramarital" sex: is there an increased risk for HIV transmission? A study of male couples of mixed HIV status.

This report describes the sexual behavior with "extramarital" partners of men who are in committed relationships with men of opposite HIV status. We examined the rates of unprotected anal sex with outside partners and compared these rates with the prevalence of such activity within the couple, during the year prior to the assessment. Seventy-five couples were interviewed, of whom 50 (67%) reported sex outside of the primary relationship by one or both members of the couple. Rates of unprotected anal sex with one-night stands and "other" partners were 25% and 33%, respectively among men who engaged in anal sex with such partners. In contrast, 54% of the men who engaged in anal sex with their primary partner did not always use condoms. Data from men who engaged in anal sex with both their primary partner and one-night stand(s) revealed that condoms were used less frequently within the primary relationship when the HIV negative men were the insertive partner; otherwise the rates of unprotected anal sex were similar. Approximately 75% of HIV negative men who engaged in receptive anal sex always used condoms, and a similar proportion of HIV positive men always used condoms during insertive anal sex, regardless of partner type. The vast majority of unprotected anal sex occurred without ejaculation inside the rectum. Unprotected oral sex was highly prevalent regardless of partner type. Implications for public health policy and primary prevention research are discussed.