Pilot evaluation of a second-generation electronic pill box for adherence to Bedaquiline and antiretroviral therapy in drug-resistant TB/HIV co-infected patients in KwaZulu-Natal, South Africa.

BACKGROUND: The introduction of Bedaquiline, the first new antimycobacterial drug in over 40 years, has highlighted the critical importance of medication adherence in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug-resistance and derive sustained benefit. Real-time electronic dose monitoring (EDM) accurately measures adherence and allows for titration of adherence support for anti-retroviral therapy (ART). The goal of this study was to evaluate the accuracy and acceptability of a next-generation electronic pillbox (Wisepill RT2000) for Bedaquiline-containing TB regimens. METHODS: Eligible patients were DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline-containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover design was used to evaluate levels of adherence and patient acceptance of EDM. Each patient was given a Wisepill device which was filled with ART, Levofloxacin or Bedaquiline over three consecutive weeks. Medication adherence was measured using Wisepill counts, patient-reported seven-day recall, and weekly pill count. An open-ended qualitative questionnaire at the end of the study evaluated participant acceptability of the Wisepill device. RESULTS: We enrolled 21 DR-TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from August through September 2016. In aggregate patients were similarly adherent to Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count. Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting non-adherence events (p = 0.02). Patients reported positive experiences with Wisepill and expressed willingness to use the device during a full course of DR-TB treatment. There were no concerns about stigma, confidentiality, or remote monitoring. CONCLUSION: In this pilot study patients were highly adherent to Bedaquiline by all adherence measures. However, there was lower adherence to ART by pill count and Wisepill suggesting a possible challenge for adherence with ART. The use of EDM identified significantly more missed doses than seven-day recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and is a promising modality to support and monitor medication adherence in complex treatment regimens.

Training social workers to enhance patient-centered care for drug-resistant TB-HIV in South Africa.

KwaZulu-Natal, South Africa, is the epicenter of an epidemic of drug-resistant tuberculosis (DR-TB) and human immunodeficiency virus (HIV) co-infection, characterized by low rates of medication adherence and retention in care. Social workers may have a unique role to play in improving DR-TB-HIV outcomes. We designed, implemented and evaluated a model-based pilot training course on patient-centered care, treatment literacy in DR-TB and HIV coinfection, patient support group facilitation, and self-care. Ten social workers participated in a 1-day training course. Post-training questionnaire scores showed significant overall gains (P = 0.003). A brief training intervention may be a useful and feasible way to engage social workers in patient-centered care for DR-TB and HIV coinfection.

Le KwaZulu-Natal, en Afrique du Sud, est l'épicentre d'une épidémie de coïnfection par la tuberculose pharmacorésistante (TB-DR) et le virus de l'immunodéficience humaine caractérisée par des taux faibles d'adhérence aux médicaments et de rétention en soins. Les travailleurs sociaux pourraient avoir un rôle unique dans l'amélioration des résultats de la coïnfection TB-DR et VIH. Nous avons conçu, mis en œuvre et évalué une formation pilote basée sur un modèle de soins centré sur le patient, de connaissance du traitement de la coïnfection TB-DR et VIH, de facilitation des groupes de soutien aux patients et de soins auto-administrés. Dix travailleurs sociaux ont participé à une formation d'un jour. Les scores des questionnaires après la formation ont montré des gains d'ensemble significatifs (P = 0,003). Une brève intervention de formation pourrait être une façon utile et faisable d'engager les travailleurs sociaux dans la prise en charge centrée sur le patient coïnfecté par la TB-DR et le VIH.

KwaZulu-Natal, en Suráfrica, es el epicentro de una epidemia de coinfección por el virus de la inmunodeficiencia humana (VIH) y la tuberculosis farmacorresistente (TB-DR), que se caracteriza por bajas tasas de cumplimiento terapéutico y una deficiente retención en la atención. Los trabajadores sociales pueden cumplir una función muy útil en el mejoramiento de los desenlaces clínicos de estos casos. En el presente artículo se describe el diseño, la ejecución y la evaluación de un curso experimental de capacitación a partir de un modelo, sobre la atención centrada en el paciente, la divulgación terapéutica relacionada con la coinfección por el VIH y la TB-DR, la facilitación en grupos de apoyo de pacientes y la autoasistencia. Diez trabajadores sociales participaron en un curso de capacitación de un día de duración. La puntuación de los cuestionarios posteriores a la capacitación reveló progresos notables en general (P = 0,003). Una intervención breve de capacitación puede representar un medio útil y viable para fomentar la participación de los trabajadores sociales en la atención centrada en el paciente de los casos de coinfección por el VIH y la TB-DR.

Impact of nurse-delivered community-based CD4 services on facilitating pre-ART care in rural South Africa.

BACKGROUND: HIV testing, diagnosis and treatment programs have expanded globally, particularly in resource-limited settings. Diagnosis must be followed by determination of treatment eligibility and referral to care prior to initiation of antiretroviral treatment (ART). However, barriers and delays along these early steps in the treatment cascade may impede successful ART initiation. New strategies are needed to facilitate the treatment cascade. We evaluated the role of on site CD4+ T cell count phlebotomy services by nurses in facilitating pre-ART care in a community-based voluntary counseling and testing program (CBVCT) in rural South Africa. METHODS: We retrospectively evaluated CBVCT services during five continuous time periods over three years: three periods when a nurse was present on site, and two periods when the nurse was absent. When a nurse was present, CD4 count phlebotomy was performed immediately after HIV testing to determine ART eligibility. When a nurse was absent, patients were referred to their local primary care clinic for CD4 testing. For each period, we determined the proportion of HIV-positive community members who completed CD4 testing, received notification of CD4 count results, as well as the time to test completion and result notification. RESULTS: Between 2010 and 2013, 7213 individuals accessed CBVCT services; of these, 620 (8.6 %) individuals were HIV-positive, 205 (33.1 %) were eligible for ART according to South African national CD4 count criteria, and 78 (38.0 % of those eligible) initiated ART. During the periods when a professional nurse was available to provide CD4 phlebotomy services, HIV-positive clients were significantly more likely to complete CD4 testing than during periods when these services were not available (85.5 % vs. 37.3 %, p < 0.001). Additionally, when nurses were present, individuals were significantly more likely to be notified of CD4 results (60.6 % vs. 26.7 %, p <0.001). The time from HIV screening to CD4 test completion was also significantly shorter during nurse presence than nurse absence (median 8 days (IQR 4-19) vs. 35 days (IQR 15-131), p < 0.001). CONCLUSIONS: These findings indicate that in addition to CBVCT, availability of on site CD4 phlebotomy may reduce loss along the pre-ART care cascade and facilitate timely entry into HIV care.

Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV.

BACKGROUND: Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE: To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION: Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION: It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

Transmission risk behaviour at enrolment in participants in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: A proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve Strategic Timing of AntiRetroviral Treatment (START) trial participants. METHODS: All START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D) in the past two months. RESULTS: A total of 4601 of 4685 HIV-positive participants (98%) completed the questionnaire [2559 men who have sex with men (MSM), 803 heterosexual men and 1239 women]. Region of recruitment was Europe/Israel, 33%; South America/Mexico, 25%; Africa, 22%; other, 21%. Median age was 36 years [interquartile range (IQR) 29, 44 years]. Forty-five per cent reported white ethnicity and 31% black ethnicity. Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL. Seventeen per cent (767 of 4601) reported CLS-D; 20% of MSM compared with 10% of heterosexual men and 14% of women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures (reported by more than half of those who had CLS-D) were seropositioning (receptive anal CLS-D only) or withdrawal (insertive anal CLS-D always without ejaculation). CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe. Knowledge of ART impact on transmission risk was low. CONCLUSIONS: A substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures.

Improved survival in multidrug-resistant tuberculosis patients receiving integrated tuberculosis and antiretroviral treatment in the SAPiT Trial.

BACKGROUND: The therapeutic effects of antiretroviral treatment (ART) in patients with multidrug-resistant tuberculosis (MDR-TB) and human immunodeficiency virus (HIV) infection have not been established. OBJECTIVE: To assess therapeutic outcomes of integrating ART with treatment for MDR-TB. DESIGN: A subgroup of MDR-TB patients from a randomised controlled trial, the SAPiT (Starting Antiretroviral Therapy at Three Points in Tuberculosis) study, conducted in an out-patient clinic in Durban, South Africa, from 2008 to 2012. METHODS: Clinical outcomes at 18 months were compared in patients randomised to receive ART within 12 weeks of initiating standard first-line anti-tuberculosis treatment with those who commenced ART after completing anti-tuberculosis treatment. RESULTS: Mycobacterium tuberculosis drug susceptibility results were available in 489 (76%) of 642 SAPiT patients: 23 had MDR-TB, 14 in the integrated treatment arm and 9 in the sequential treatment arm. At 18 months, the mortality rate was 11.9/100 person-years (py; 95%CI 1.4-42.8) in the combined integrated treatment arm and 56.0/100 py (95%CI 18.2-130.8) in the sequential treatment arm (hazard ratio adjusted for baseline CD4 count and whether MDR-TB treatment was initiated: 0.14; 95%CI 0.02-0.94, P = 0.04). CONCLUSION: Despite the small sample size, the 86% reduction in mortality due to early initiation of ART in MDR-TB patients was statistically significant.

'Cough officer' nurses in a general medical clinic successfully detect drug-susceptible and -resistant tuberculosis.

SETTING: Intensive case finding (ICF) for tuberculosis (TB) is recommended by the World Health Organization among known human immunodeficiency virus (HIV) patients. However, ICF may also be appropriate in generalized patient populations. OBJECTIVE: To evaluate the yield of ICF in a general medical clinic in a high HIV prevalence setting. METHODS: A nurse designated as a 'cough officer' identified clinic attendees with cough of >2 weeks and collected sputum for evaluation at the hospital and provincial referral laboratories. We retrospectively evaluated the number and proportion of patients with microbiologically confirmed TB identified in 2007-2008. RESULTS: Among 56 207 clinic attendees, 1442 (2.6%) TB suspects were identified and 122 (8.5%) were sputum Ziehl-Neelsen (ZN) positive. Of 389 available results, 72 (18.5%) were auramine-positive and 99 (25.4%) were culture-positive; multidrug-resistant and extensively drug-resistant TB were identified in 16 (16.2%). The number needed to screen was 11.8 patients to identify one ZN-positive case and 3.9 to identify one culture-positive case. CONCLUSIONS: A nurse-facilitated cough officer program successfully identified TB suspects and drug-susceptible and drug-resistant TB. Culture was more sensitive for TB screening and critical for identifying drug resistance. ICF is operationally feasible, and should be expanded to general medical clinics in high HIV and TB prevalence, resource-limited settings.

Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care.

SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.

Tuberculosis infection control in a high drug-resistance setting in rural South Africa: information, motivation, and behavioral skills.

BACKGROUND: Tuberculosis (TB) is transmitted in resource-limited facilities where TB infection control (IC) is poorly implemented. Theory-based behavioral models can potentially improve IC practices. METHODS: The present study used an anonymous questionnaire to assess healthcare worker (HCW) TB IC information, motivation, and behavioral skills (IMB) and implementation in two resource-limited rural South African hospitals with prevalent drug-resistant TB. RESULTS: Between June and August 2010, 198 surveys were completed. Although the respondents demonstrated information proficiency and positive motivation, 22.8% did not consider TB IC to be worthwhile. Most tasks were rated as easy by survey participants, but responding HCWs highlighted challenges in discrete behavioral skills. The majority of responding HCWs reported that they always wore respirators (54.3%), instructed patients on cough hygiene (63.0%), and ensured natural ventilation (67.4%) in high-risk areas. Most respondents (74.0%) knew their HIV status. Social support items correlated with the implementation of the first three aforementioned practices but not with the respondents' knowledge of their HIV status. In most cases, motivation and behavioral skills, but not information, were associated with implementation. CONCLUSION: HCWs in rural South African hospitals with high drug-resistance demonstrated moderate IMB and implementation of TB IC. Improvement efforts should emphasize the development of HCW motivation and behavioral skills as well as social support from colleagues and supervisors. Such interventions should be informed by baseline IMB assessments. In the present study, a trimmed/modified IMB model helped characterize TB IC implementation.

Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting.

SETTING: Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates. OBJECTIVE: To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa. DESIGN: Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB. RESULTS: Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ≤ 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ≤ 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009). CONCLUSIONS: Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.

Tuberculosis infection control in rural South Africa: survey of knowledge, attitude and practice in hospital staff.

A baseline assessment of tuberculosis infection control (TB IC) knowledge, attitude and practice (KAP) was conducted among staff in a resource-limited rural South African hospital where nosocomially transmitted multi- and extensively drug-resistant (M/XDR) TB had been reported. Assessment consisted of anonymous questionnaires and direct observation during July-September 2007, soon after the report of M/XDR-TB. Data were obtained from 57 questionnaires and 10h of direct observation. While knowledge and attitudes were generally supportive of TB IC implementation, 49.1% of staff felt that the hospital did not care about them and/or was not working to prevent staff TB infections, and 42.9% were less willing to continue as a healthcare worker because of staff TB/MDR-TB/XDR-TB deaths. Practices were variable. The recent appointment of an IC officer and implementation of natural ventilation were strengths, but the facility lacked a TB IC policy, the patient TB screening process was inadequate, and 41.5% of respondents were unaware of their personal human immunodeficiency virus (HIV) status. Respondents reported a number of barriers to TB IC implementation such as concerns about the confidentiality of staff health information, the stigma of TB and HIV, inadequate resources, and patient non-compliance. Assessment of staff KAP provided useful data regarding deficits and barriers to TB IC, and helped to focus subsequent IC strategies. Given the critical importance of reducing nosocomial TB transmission, it is recommended that facilities should conduct simplified TB IC assessment, ensure the confidentiality of staff health information, address the stigma of TB/HIV, and implement multi-faceted TB IC facility and behavioural change interventions. Behavioural science methods have the potential to improve TB IC research and implementation.

Household contact investigation of multidrug-resistant and extensively drug-resistant tuberculosis in a high HIV prevalence setting.

SETTING: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are now a nationwide epidemic in South Africa. Epidemiological data suggest nosocomial transmission as the primary route of spread; however, transmission among household contacts has not yet been investigated. OBJECTIVE: To determine the incidence rates of MDR- and XDR-TB among household contacts of MDR- and XDR-TB index cases diagnosed between January 2005 and September 2008 in a high human immunodeficiency virus prevalence setting. DESIGN: Prospective, observational study evaluating adult household contacts for active TB by culture and drug susceptibility testing at index case diagnosis and again 1 year later. Outcomes were incidence and time to diagnosis of MDR- and XDR-TB. RESULTS: A total of 1766 contacts of 221 MDR-TB and 287 XDR-TB index cases were screened. Of 793 contacts of MDR-TB index cases, 14 (1.8%) were diagnosed with MDR-TB (incidence 1765/100 000); 19 (2.0%) of 973 XDR-TB contacts had XDR-TB (incidence 1952/100 000). Median time to diagnosis of household cases was 70 days (interquartile range 57-89). CONCLUSION: Incidence rates of MDR- and XDR-TB among household contacts were extremely high, with most secondary cases occurring shortly after the diagnosis of the index case. Active case finding of drug-resistant TB is a high-yield public health activity and must be a priority, as early diagnosis may stem further disease spread and improve survival.

Extensively drug-resistant tuberculosis in children with human immunodeficiency virus in rural South Africa.

SETTING: Extensively drug-resistant tuberculosis (XDR-TB) has been documented worldwide, but reports of XDR-TB in children are extremely limited. OBJECTIVE: To report the characteristics of pediatric XDR-TB patients in rural South Africa. DESIGN: We retrospectively reviewed children with sputum culture-confirmed XDR-TB from Tugela Ferry, South Africa, from January 2006 to December 2007. Demographic, clinical and microbiologic data were abstracted from medical records. RESULTS: Four children aged 6-8 years with XDR-TB were reviewed. Two had previous histories of TB. All were human immunodeficiency virus (HIV) infected orphans; three received highly active antiretroviral therapy (HAART) before XDR-TB diagnosis. All had clinical and radiographic improvement and sputum culture conversion while on standardized XDR-TB treatment and HAART. Two tolerated concomitant XDR-TB and HIV treatment well. Two experienced neuropsychiatric side effects related to cycloserine. All have survived >24 months and all were cured. Prior to XDR-TB diagnosis, the children had resided in the hospital's pediatric ward for a median of 8 months (range 5-17), including a 3-month overlapping period. CONCLUSIONS: XDR-TB is a microbiologic diagnosis that, even with HIV co-infection, can be successfully identified. Concurrent XDR-TB and HIV therapy is feasible and effective in children, although more research is needed into potential overlapping toxicities. Nosocomial transmission is suggested, calling for infection control policies in pediatric wards.

Decentralised management of drug-resistant tuberculosis (MDR- and XDR-TB) in South Africa: an alternative model of care.

SETTING: A growing number of cases of extensively drug-resistant tuberculosis (XDR-TB) have been reported from KwaZulu-Natal, South Africa. OBJECTIVE: To propose an alternative model to centralised care that can be implemented to alleviate the current emergency. DISCUSSION: The current failing TB programme could be improved by borrowing strategies such as decentralisation of care, treatment expertise, high levels of treatment adherence and successful outcomes, all of which have been successfully implemented in the human immunodeficiency virus programme. Patients with multidrug-resistant or XDR-TB could be admitted to institutions closer to their homes for treatment with subsequent discharge to home-based care. CONCLUSION: The longer we support a failed system or wait for a perfect solution, the more the current devastation will continue to grow.

Characteristics of HIV-1-associated Kaposi's sarcoma among women and men in South Africa.

Despite the increase of HIV-1-associated Kaposi's sarcoma (KS), little is known about HIV-associated KS in the African setting, particularly among women. A descriptive study of the demographic, clinical, immunological and virological features of AIDS-associated KS from KwaZulu-Natal, South Africa was undertaken. Consecutively, recruited patients were clinically staged; CD4/CD8 cell counts, HIV-1 viral loads and clinical parameters were evaluated. Of the 152 patients (77 male and 75 female) 99% were black. Females were significantly younger (P = 0.02) and had poorer disease prognosis (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4, P = 0.003) and were more likely to have extensive cutaneous KS when compared with males (OR = 3.1, 95% CI = 1.4-6.7, P = 0.003). One-third of patients had coexisting HIV-related disease, most commonly tuberculosis, and these were more frequent in females (56.7 vs. 43.3%). In conclusion, HIV-associated KS in South Africans has an equal female-to-male ratio. Females are younger and have more severe disease than males.

A randomized comparison of two instruments for measuring self-reported antiretroviral adherence.

A randomised trial compared two instruments for assessing self-reported adherence to antiretroviral medications: (1) a day-by-day recall instrument that elicited the number of missed doses in each of the prior three days (3-day instrument; n=64) and (2) a general recall instrument that elicited an estimate of proportion of pills taken during the prior seven days (7-day instrument; n=70). Adherence was measured at study visits over 12 months among participants in a clinical trial assessing treatment strategies for individuals with virologic failure and multidrug-resistant HIV. Participants had a median (interquartile range) of 133 (41-264) CD4 cells/ml(3) and a median of 10 major HIV resistance mutations at baseline. Mean adherence levels were 90-98% throughout the study. There was a greater trend in the likelihood of 100% adherence when measured by the 3-day versus the 7-day instrument (odds ratio (OR)=1.45; p=0.06). The likelihood of consistent 100% adherence measured by either instrument decreased over time (p<0.001). Participants reporting 100% adherence at more than half of study visits had better virologic and immunologic outcomes at month-12 compared to those reporting 100% adherence at half or fewer visits (HIV RNA decline of 0.96 versus 0.51 log, respectively, p=0.02; and CD4 cell increase of 51.0 versus 17.8 cells, p=0.04). This study demonstrated the utility of the general 7-day recall adherence self-report instrument as well as the 3-day day-by-day recall adherence self-report instrument for measuring antiretroviral adherence. Self-reported adherence was significantly associated with virologic and immunologic outcomes in this population with advanced drug-resistant HIV disease.

Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence.

This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ARTadherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4+ cell count 230 cells/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p < 0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with < 80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained.

Trust and the acceptance of and adherence to antiretroviral therapy.

BACKGROUND: Antiretroviral therapy (ART) has resulted in reduced AIDS incidence and mortality. Socially marginalized individuals with HIV infection, particularly injection drug users (IDUs), have received less ART and derived less benefit than others. Little is known about the therapeutic process necessary to promote acceptance of and adherence to ART among marginalized HIV-infected populations. We report on the correlates of both acceptance of and adherence to ART among HIV infected prisoners, most of whom are IDUs. DESIGN: Using a cross-sectional survey design within four ambulatory prison HIV clinics, 205 HIV-infected prisoners eligible for ART were recruited between March and October 1996. MEASUREMENTS: Detailed interviews were conducted that included personal characteristics, health status and beliefs, and validated standardized scales measuring depression, health locus of control, social desirability and trust in physician, medical institutions and society. Acceptance and adherence were documented by self-report and validated for a subset by pharmacy review. Clinical information was obtained from standardized chart review. Adherence was defined as having taken > or = 80% of ART. RESULTS: The acceptance of (80%) and adherence to (84%) ART among this group of prisoners was high. Multiple regression models demonstrated that correlates of acceptance of and adherence to ART differed. Acceptance was associated with trust in physician (8% increase for each unit increase with trust in physician scale) and trust in HIV medications (threefold reduction for those mistrustful of medication). Side effects (OR = 0.09), social isolation (OR = 0.08), and complexity of the antiretroviral regimen (OR = 0.33) were associated with decreased adherence. The prevalence of health beliefs suggesting an adverse relationship between ART and drugs of abuse was high (range 59 to 77%). Adherence did not differ among those receiving directly observed therapy (82%) or self-administration (85%). CONCLUSIONS: ART can be successfully administered within a correctional setting. Trust and the therapeutic relationship between patient and physician remain central in the ART initiation process. Characteristics of the therapeutic agents and the degree of social isolation predict adherence. These results may inform the design of interventions to improve both acceptance of and adherence to ART particularly among marginalized populations who have not derived full benefit from these potent new therapies.