Person:

Safren, Steven A.

Background: PEARLS, a large scale trial of antiretroviral therapy (ART) for HIV (n = 1,571, 9 countries, 4 continents), found that a once-daily protease inhibitor (PI) based regimen (ATV+DDI+FTC), but not a once-daily non-nucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) regimen (EFV+FTC/TDF), had inferior efficacy compared to a standard of care twice-daily NNRTI/NRTI regimen (EFV+3TC/ZDV). The present study examined non-adherence in PEARLS. Methods: Outcomes: non-adherence assessed by pill count and by self-report, and time to treatment failure. Longitudinal predictors: regimen, quality of life (general health perceptions = QOL-health, mental health = QOL-mental health), social support, substance use, binge drinking, and sexual behaviors. “Life-Steps” adherence counseling was provided. Results: In both pill-count and self-report multivariable models, both once-a-day regimens had lower levels of non-adherence than the twice-a-day standard of care regimen; although these associations attenuated with time in the self-report model. In both multivariable models, hard-drug use was associated with non-adherence, living in Africa and better QOL-health were associated with less non-adherence. According to pill-count, unprotected sex was associated with non-adherence. According to self-report, soft-drug use was associated with non-adherence and living in Asia was associated with less non-adherence. Both pill-count (HR = 1.55, 95% CI: 1.15, 2.09, p<.01) and self-report (HR = 1.13, 95% CI: 1.08, 1.13, p<.01) non-adherence were significant predictors of treatment failure over 72 weeks. In multivariable models (including pill-count or self-report nonadherence), worse QOL-health, age group (younger), and region were also significant predictors of treatment failure. Conclusion: In the context of a large, multi-national, multi-continent, clinical trial there were variations in adherence over time, with more simplified regimens generally being associated with better adherence. Additionally, variables such as QOL-health, regimen, drug-use, and region play a role. Self-report and pill-count adherence, as well as additional psychosocial variables, such QOL-health, age, and region, were, in turn, associated with treatment failure.

Background: Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Methods and Findings: Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants—all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%–100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%–100%) by unannounced pill counts and 97.2% (90.6%–100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. Conclusions: The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary

Introduction: Safer conception strategies create opportunities for HIV-serodiscordant couples to realize fertility goals and minimize periconception HIV transmission. Patient–provider communication about fertility goals is the first step in safer conception counseling. Methods: We explored provider practices of assessing fertility intentions among HIV-infected men and women, attitudes toward people living with HIV (PLWH) having children, and knowledge and provision of safer conception advice. We conducted in-depth interviews (9 counselors, 15 nurses, 5 doctors) and focus group discussions (6 counselors, 7 professional nurses) in eThekwini District, South Africa. Data were translated, transcribed, and analyzed using content analysis with NVivo10 software. Results: Among 42 participants, median age was 41 (range, 28–60) years, 93% (39) were women, and median years worked in the clinic was 7 (range, 1–27). Some providers assessed women's, not men's, plans for having children at antiretroviral therapy initiation, to avoid fetal exposure to efavirenz. When conducted, reproductive counseling included CD4 cell count and HIV viral load assessment, advising mutual HIV status disclosure, and referral to another provider. Barriers to safer conception counseling included provider assumptions of HIV seroconcordance, low knowledge of safer conception strategies, personal feelings toward PLWH having children, and challenges to tailoring safer sex messages. Conclusions: Providers need information about HIV serodiscordance and safer conception strategies to move beyond discussing only perinatal transmission and maternal health for PLWH who choose to conceive. Safer conception counseling may be more feasible if the message is distilled to delaying conception attempts until the infected partner is on antiretroviral therapy. Designated and motivated nurse providers may be required to provide comprehensive safer conception counseling.

OBJECTIVE To assess the validity of self-report measures of diabetes medication adherence and evaluate the effect of depression on the validity of these reports. RESEARCH DESIGN AND METHODS Adults with type 2 diabetes, treated with oral medications, completed a set of medication adherence self-reports that varied response scales and time frames, were administered structured clinical interviews for depression, and provided blood samples for HbA1c as part of a screening for an intervention study. A subsample of participants with HbA1c ≥7.0% and clinically significant depression received Medication Event Monitoring System (MEMS) bottle caps to record adherence. Analyses examined relationships between adherence measures and HbA1c and, in the subsample, MEMS. Moderated linear regression evaluated whether depression severity modified relationships with HbA1c. RESULTS Participant (n = 170, 57% men, 81% white, mean HbA1c 8.3% [SD, 1.7]) adherence self-reports were significantly (r = −0.18 to −0.28; P < 0.03) associated with lower HbA1c. In the subsample (n = 88), all self-reports were significantly (r = 0.35 to 0.55; P ≤ 0.001) associated with MEMS-measured adherence. Depression significantly moderated the relationship between three of six self-reports and HbA1c; at high levels of depression, associations with HbA1c became nonsignificant. CONCLUSIONS Results support the validity of easily administered self-reports for diabetes medication adherence. One-month, percentage-based ratings of adherence had the strongest associations with MEMS and HbA1c; those requiring the report of missed doses had weaker associations. One-week self-ratings and measures that require respondents to record the number of missed doses appear to be vulnerable to bias from depression severity.

In assessing the mental health of HIV/AIDS-affected children and adolescents in Sub-Saharan Africa, researchers often employ mental health measures developed in other settings. However, measures derived from standard Western psychiatric criteria are frequently based on conceptual models of illness or terminology that may or may not be an appropriate for diverse populations. Understanding local perceptions of mental health problems can aid in the selection or creation of appropriate measures. This study used qualitative methodologies (Free Listing [FL], Key Informant [KI] interviews, and Clinician Interviews [C-KIs]) to understand local perceptions of mental health problems facing HIV/AIDS-affected youth in Rwinkwavu, Rwanda. Several syndrome terms were identified by participants: agahinda kenshi, kwiheba, guhangayika, ihahamuka, umushiha and uburara. While these local syndromes share some similarities with Western mood, anxiety, and conduct disorders, they also contain important culture-specific features and gradations of severity. Our findings underscore the importance of understanding local manifestations of mental health syndromes when conducting mental health assessments and when planning interventions for HIV/AIDS-affected children and adolescents in diverse settings.

Men who have sex with men (MSM) in India have an HIV seroprevalence 22 times greater than the country’s general population and face unique challenges that may hinder the effectiveness of current HIV prevention efforts. To obtain an understanding of the logistical and sociocultural barriers MSM experience while accessing HIV prevention services, focus groups and key informant interviews were conducted with 55 MSM in Chennai, India. Qualitative data were analyzed using descriptive qualitative content analysis. Sixty-five percent of participants identified as kothi (receptive partners), 9% as panthi (insertive partners), 22% as double decker (receptive and insertive), and 4% did not disclose. Themes included: (a) fatigue with current HIV risk reduction messages; (b) increased need for non-judgmental and confidential services; and (c) inclusion of content that acknowledges individual and structural-level determinants of risk such as low self-esteem, depression, and social discrimination. MSM interventions may benefit from approaches that address multilevel psychosocial factors, including skills building and strategies to foster self-acceptance and increased social support.

OBJECTIVE—Depression is common in patients with diabetes and is associated with worse treatment outcomes. Its relationship to treatment adherence, however, has not been systematically reviewed. We used meta-analysis to examine the relationship between depression and treatment nonadherence in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS—We searched MEDLINE and PsycINFO databases for all studies published by June 2007 and reviewed references of published articles. Meta-analytic procedures were used to estimate the effect size r in a random effects model. Significance values, weighted effect sizes, 95% CIs, and tests of homogeneity of variance were calculated. RESULTS—Results from 47 independent samples showed that depression was significantly associated with nonadherence to the diabetes treatment regimen (z = 9.97, P < 0.0001). The weighted effect size was near the medium range (r = 0.21, 95% CI 0.17–0.25). Moderator analyses showed that the effect was significantly larger in studies that measured self-care as a continuous versus categorical variable (P = 0.001). Effect sizes were largest for missed medical appointments and composite measures of self-care (r values = 0.31, 0.29). Moderation analyses suggest that effects for most other types of self-care are also near the medium range, especially in studies with stronger methodologies. CONCLUSIONS—These findings demonstrate a significant association between depression and treatment nonadherence in patients with diabetes. Studies that used stronger methodologies had larger effects. Treatment nonadherence may represent an important pathway between depression and worse diabetes clinical outcomes.

OBJECTIVE To test cognitive behavioral therapy for adherence and depression (CBT-AD) in type 2 diabetes. We hypothesized that CBT-AD would improve adherence; depression; and, secondarily, hemoglobin A1c (A1C). RESEARCH DESIGN AND METHODS Eighty-seven adults with unipolar depression and uncontrolled type 2 diabetes received enhanced treatment as usual (ETAU), including medication adherence, self-monitoring of blood glucose (SMBG), and lifestyle counseling; a provider letter documented psychiatric diagnoses. Those randomized to the intervention arm also received 9–11 sessions of CBT-AD. RESULTS Immediately after acute treatment (4 months), adjusting for baseline, CBT-AD had 20.7 percentage points greater oral medication adherence on electronic pill cap (95% CI −31.14 to −10.22, P = 0.000); 30.2 percentage points greater SMBG adherence through glucometer downloads (95% CI −42.95 to −17.37, P = 0.000); 6.44 points lower depression scores on the Montgomery-Asberg Depression Rating Scale (95% CI 2.33–10.56, P = 0.002); 0.74 points lower on the Clinical Global Impression (95% CI 0.16–1.32, P = 0.01); and 0.72 units lower A1C (95% CI 0.29–1.15, P = 0.001) relative to ETAU. Analyses of 4-, 8-, and 12-month follow-up time points indicated that CBT-AD maintained 24.3 percentage points higher medication adherence (95% CI −38.2 to −10.3, P = 0.001); 16.9 percentage points greater SMBG adherence (95% CI −33.3 to −0.5, P = 0.043); and 0.63 units lower A1C (95% CI 0.06–1.2, P = 0.03) after acute treatment ended. For depression, there was some evidence of continued improvement posttreatment, but no between-group differences. CONCLUSIONS CBT-AD is an effective intervention for adherence, depression, and glycemic control, with enduring and clinically meaningful benefits for diabetes self-management and glycemic control in adults with type 2 diabetes and depression.

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.