Dennis Israelski

Treatment of Toxoplasmic Encephalitis in Patients with AIDS: A Randomized Trial Comparing Pyrimethamine plus Clindamycin to Pyrimethamine plus Sulfadiazine

OBJECTIVE To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen. SETTING University hospitals. PATIENTS Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable. INTERVENTIONS Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks. MEASUREMENTS AND MAIN RESULTS There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover. CONCLUSIONS The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.

Mutation Patterns and Structural Correlates in Human Immunodeficiency Virus Type 1 Protease following Different Protease Inhibitor Treatments

ABSTRACT Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four or more protease inhibitors. Mutations at 45 of the 99 amino acid positions in the protease—including 22 not previously associated with drug resistance—were significantly associated with protease inhibitor treatment. Mutations at 17 of the remaining 99 positions were polymorphic but not associated with drug treatment. Pairs and clusters of correlated (covarying) mutations were significantly more likely to occur in treated than in untreated persons: 115 versus 23 pairs and 30 versus 2 clusters, respectively. Of the 115 statistically significant pairs of covarying residues in the treated isolates, 59 were within 8 Å of each other—many more than would be expected by chance. In summary, nearly one-half of HIV-1 protease positions are under selective drug pressure, including many residues not previously associated with drug resistance. Structural factors appear to be responsible for the high frequency of covariation among many of the protease residues. The presence of mutational clusters provides insight into the complex mutational patterns required for HIV-1 protease inhibitor resistance.

Community health workers and mobile technology: a systematic review of the literature.

Introduction In low-resource settings, community health workers are frontline providers who shoulder the health service delivery burden. Increasingly, mobile technologies are developed, tested, and deployed with community health workers to facilitate tasks and improve outcomes. We reviewed the evidence for the use of mobile technology by community health workers to identify opportunities and challenges for strengthening health systems in resource-constrained settings. Methods We conducted a systematic review of peer-reviewed literature from health, medical, social science, and engineering databases, using PRISMA guidelines. We identified a total of 25 unique full-text research articles on community health workers and their use of mobile technology for the delivery of health services. Results Community health workers have used mobile tools to advance a broad range of health aims throughout the globe, particularly maternal and child health, HIV/AIDS, and sexual and reproductive health. Most commonly, community health workers use mobile technology to collect field-based health data, receive alerts and reminders, facilitate health education sessions, and conduct person-to-person communication. Programmatic efforts to strengthen health service delivery focus on improving adherence to standards and guidelines, community education and training, and programmatic leadership and management practices. Those studies that evaluated program outcomes provided some evidence that mobile tools help community health workers to improve the quality of care provided, efficiency of services, and capacity for program monitoring. Discussion Evidence suggests mobile technology presents promising opportunities to improve the range and quality of services provided by community health workers. Small-scale efforts, pilot projects, and preliminary descriptive studies are increasing, and there is a trend toward using feasible and acceptable interventions that lead to positive program outcomes through operational improvements and rigorous study designs. Programmatic and scientific gaps will need to be addressed by global leaders as they advance the use and assessment of mobile technology tools for community health workers.

Social Support, Substance Use, and Denial in Relationship to Antiretroviral Treatment Adherence among HIV-Infected Persons

This study examined the relationship of adherence to antiretroviral treatment with three types of social support (partner, friends, and family) and use of two coping strategies (denial and substance use). Participants were 73 men and women with HIV infection drawn from a larger sample of 186 clinical trial patients. Based on inclusion criteria, parent trial participants taking antiretroviral therapies, and those with complete data on self-reported measures of adherence were considered eligible for the present study. Overall, 26% of participants were found to be nonadherent, which was defined as one or more missed doses of treatment in the prior 4-day period. Logistic regression analysis was conducted to determine associations of sociodemographic and psychosocial variables with adherence to antiretroviral regimen. Results indicated that heterosexual participants (p < 0.01) and participants of Latino ethnicity (p < 0.05) were significantly more likely to report missed medications. Perceived satisfaction with support from a partner was associated with taking antiretroviral therapy as prescribed, whereas satisfaction with support from friends and from family was not significantly related to adherence. Examination of coping strategies showed that participants reporting drug and alcohol use (p <.05) to cope with HIV-related stress were more likely to be nonadherent. These findings call for adherence interventions designed to address barriers and strengths, such as community norms or traditional cultural values, specific to certain populations. Furthermore, couple-based approaches enlisting partner support may help persons living with HIV to adhere to antiretroviral regimens.

Coping, Social Support, and Attachment Style as Psychosocial Correlates of Adjustment in Men and Women with HIV/AIDS

The purpose of this study was to examine psychosocial correlates of adjustment to HIV/AIDS in a sample of 137 HIV-positive persons (78 men and 59 women). Multiple regression analysis was used to examine relationships between perceived quality of general social support, three attachment styles, and three coping styles with total score on Positive States of Mind Scale (PSOMS), our measure of adjustment. The influence of demographic and medical status variables was also accounted for. PSOMS total score was significantly associated with greater satisfaction with social support related to HIV/AIDS, more secure attachment style, and less use of behavioral disengagement in coping with HIV/AIDS. These results indicate that for people with HIV or AIDS, those individuals who are more satisfied with their relationships, securely engaged with others, and more directly engaged with their illness are more likely to experience positive adjustment. Implications for physical health outcome and opportunities for intervention are discussed.

Relationships of perceived stress to coping, attachment and social support among HIV-positive persons

The purpose of this study was to examine the relationships of coping, attachment style and perceived social support to perceived stress within a sample of HIV-positive persons. Participants were 147 HIV-positive persons (80 men and 67 women). Multiple regression analysis was used to examine the relationships of the demographic variables, AIDS status, three coping styles, three attachment styles and perceived quality of general social support with total score on the Perceived Stress Scale (PSS). PSS score was significantly associated with less income, greater use of behavioural and emotional disengagement in coping with HIV/AIDS, and less secure and more anxious attachment styles. These results indicate that HIV-positive persons who experience the greatest stress in their daily lives are those with lower incomes, those who disengage behaviourally/ emotionally in coping with their illness, and those who approach their interpersonal relationships in a less secure or more anxious style.

Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors

Objective: To characterize reverse transcriptase (RT) mutations by their association with extent of nucleoside RT inhibitor (NRTI) therapy. To identify mutational clusters in RT sequences from persons receiving multiple NRTI. Design: A total of 1210 RT sequences from persons with known antiretroviral therapy were analyzed: 641 new sequences were performed at Stanford University Hospital; 569 were previously published. Methods: Chi-square tests and logistic regression were done to identify associations between mutations and NRTI therapy. Correlation studies were done to identify mutational clusters. The Benjamini–Hochberg procedure was used to correct for multiple comparisons. Results: Mutations at 26 positions were significantly associated with NRTI including 17 known resistance mutations (positions 41, 44, 62, 65, 67, 69, 70, 74, 75, 77, 116, 118, 151, 184, 210, 215, 219) and nine previously unreported mutations (positions 20, 39, 43, 203, 208, 218, 221, 223, 228). The nine new mutations correlated linearly with number of NRTI; 777 out of 817 (95%) instances occurred with known drug resistance mutations. Positions 203, 208, 218, 221, 223, and 228 were conserved in untreated persons; positions 20, 39, and 43 were polymorphic. Most NRTI-associated mutations clustered into three groups: (i) 62, 65, 75, 77, 115, 116, 151; (ii) 41, 43, 44, 118, 208, 210, 215, 223; (iii) 67, 69, 70, 218, 219, 228. Conclusions: Mutations at nine previously unreported positions are associated with NRTI therapy. These mutations are probably accessory because they occur almost exclusively with known drug resistance mutations. Most NRTI mutations group into one of three clusters, although several (e.g., M184V) occur in multiple mutational contexts.

Psychiatric co-morbidity in vulnerable populations receiving primary care for HIV/AIDS

Abstract Considerable evidence suggests that people with HIV disease are significantly more distressed than the general population, yet psychiatric disorders are commonly under-detected in HIV care settings. This study examines the prevalence of three stress-related psychiatric diagnoses – depression, posttraumatic stress disorder (PTSD), and acute stress disorder (ASD), among a vulnerable population of HIV-infected patients. Among approximately 350 patients attending two county-based HIV primary care clinics, 210 participants were screened for diagnostic symptom criteria for depression, PTSD, and ASD. Standardized screening measures used to assess for these disorders included the Beck Depression Inventory, the Posttraumatic Stress Checklist, and the Stanford Acute Stress Questionnaire. High percentages of HIV-infected patients met screening criteria for depression (38 per cent), PTSD (34 per cent), and ASD (43 per cent). Thirty eight percent screened positively for two or more disorders. Women were more likely to meet symptom criteria for ASD than men (55 per cent vs. 38 per cent, OR=1.94, CI95 per cent=1.1–3.5). ASD was detected more commonly among African-American and white participants (51 per cent and 50 per cent respectively), compared with other ethnic groups. Latinos were least likely to express symptoms of ASD (OR=0.52, CI95 per cent=0.29–0.96). Of the 118 patients with at least one of these disorders, 51 (43 per cent) reported receiving no concurrent mental health treatment. Patients with HIV/AIDS who receive public healthcare are likely to have high rates of acute and posttraumatic stress disorders and depression. These data suggest that current clinical practices could be improved with the use of appropriate tools and procedures to screen and diagnose mental health disorders in populations with HIV/AIDS.

Posttraumatic Stress Disorder in Women Attending Human Immunodeficiency Virus Outpatient Clinics

This study examined posttraumatic stress disorder (PTSD) in human immunodeficiency virus (HIV)-positive women seeking medical care. Specifically, we examined traumatic life events, psychiatric treatment, social support, and demographic characteristics in relation to level of PTSD symptoms. We recruited and obtained informed consent from 47 ethnically diverse HIV-positive women from two HIV outpatient clinics in a county medical system. Forty-one of these women provided complete data on measures assessing demographics, traumatic life events, PTSD symptoms, social support, and psychotherapy/medical history. Analysis of the data demonstrated that a high percentage (42%) of the HIV-positive women were likely to meet criteria for full current PTSD, and an additional 22% for partial PTSD. Of the women likely with full PTSD, 59% were not receiving any psychiatric treatment, and of those likely with partial PTSD, 78% were not receiving any psychiatric treatment. Also, women reported having experienced a mean of 12 traumatic life events. As hypothesized, the level of PTSD was significantly related to the number of life events experienced (rs = 0.52, p < 0.001), and to perceived social support from friends (rs = - 0.34, p < 0.02) and family (rs = - 0.29, p < 0.05). Given the high percentages of women who were found to have experienced traumatic life events and high levels of PTSD symptoms, it seems important to assess and treat PTSD in women with HIV/acquired immune deficiency syndrome (AIDS).

mHealth for HIV Treatment & Prevention: A Systematic Review of the Literature

This systematic review assesses the published literature to describe the landscape of mobile health technology (mHealth) for HIV/AIDS and the evidence supporting the use of these tools to address the HIV prevention, care, and treatment cascade. The speed of innovation, broad range of initiatives and tools, and heterogeneity in reporting have made it difficult to uncover and synthesize knowledge on how mHealth tools might be effective in addressing the HIV pandemic. To do address this gap, a team of reviewers collected literature on the use of mobile technology for HIV/AIDS among health, engineering, and social science literature databases and analyzed a final set of 62 articles. Articles were systematically coded, assessed for scientific rigor, and sorted for HIV programmatic relevance. The review revealed evidence that mHealth tools support HIV programmatic priorities, including: linkage to care, retention in care, and adherence to antiretroviral treatment. In terms of technical features, mHealth tools facilitate alerts and reminders, data collection, direct voice communication, educational messaging, information on demand, and more. Studies were mostly descriptive with a growing number of quasi-experimental and experimental designs. There was a lack of evidence around the use of mHealth tools to address the needs of key populations, including pregnant mothers, sex workers, users of injection drugs, and men who have sex with men. The science and practice of mHealth for HIV are evolving rapidly, but still in their early stages. Small-scale efforts, pilot projects, and preliminary descriptive studies are advancing and there is a promising trend toward implementing mHealth innovation that is feasible and acceptable within low-resource settings, positive program outcomes, operational improvements, and rigorous study design