Search

ObjectivesThe introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance.MethodsWe analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations for nevirapine, efavirenz, etravirine and rilpivirine, respectively. We used linear regression to estimate the effects of RT mutations on susceptibility to each of these NNRTIs.ResultsSixteen mutations at 10 positions were significantly associated with the greatest contribution to reduced phenotypic susceptibility (≥10-fold) to one or more NNRTIs, including: 14 mutations at six positions for nevirapine (K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S); 10 mutations at six positions for efavirenz (L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S); 5 mutations at four positions for etravirine (K101P, Y181I/V, G190E and F227C); and 6 mutations at five positions for rilpivirine (L100I, K101P, Y181I/V, G190E and F227C). G190E, a mutation that causes high-level nevirapine and efavirenz resistance, also markedly reduced susceptibility to etravirine and rilpivirine. K101H, E138G, V179F and M230L mutations, associated with reduced susceptibility to etravirine and rilpivirine, were also associated with reduced susceptibility to nevirapine and/or efavirenz.ConclusionsThe identification of novel cross-resistance patterns among approved NNRTIs illustrates the need for a systematic approach for testing novel NNRTIs against clinical virus isolates with major NNRTI-resistance mutations and for testing older NNRTIs against virus isolates with mutations identified during the evaluation of a novel NNRTI.

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.

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

This study examined social support and maladaptive coping as predictors of HIV-related health symptoms. Sixty-five men and women living with HIV/AIDS completed baseline measures assessing coping strategies, social support, and HIV-related health symptoms. The sample was primarily low-income and diverse with respect to gender, ethnicity, and sexual orientation. Three, 6, and 12 months after completing baseline assessments, physical health symptoms associated with HIV disease were assessed. After controlling for demographic characteristics, CD4 T-cell count, and baseline HIV-related health symptoms, individuals reporting lower increase in HIV-related health symptoms used less venting (expressing emotional distress) as a strategy for coping with HIV. However, when satisfaction with social support was added to the model, the use of this coping strategy was no longer significant, and individuals reporting more satisfying social support were more likely to report lower increase in their HIV-related health symptoms, suggesting that social support is a robust predictor of health outcomes over time independent of coping style and baseline medical status. These findings provide further evidence that social support can buffer deleterious health outcomes among individuals with a chronic illness. Future research needs to examine mediating pathways that can explain this relationship.

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.

The HIV-1-specific humoral immune response during highly active antiretroviral therapy (HAART) has been characterized using plasma samples from 19 patients. The factors involved in the high failure rate of HAART may include, in addition to emergence of HIV strains resistant to the drugs, this response. It may interact with both virus replication and drug therapy. A strong HIV-directed humoral immune response, as measured by V3 binding antibodies and neutralizing antibody responses before HAART, correlated with future viral suppression on HAART.

The drugs efavirenz and adefovir dipivoxil appear to be beneficial in HIV patients who no longer respond to nucleotide reverse transcriptase inhibitors. This was the conclusion of a study of 33 HIV patients. Patients who had taken non-nucleoside reverse transcriptase inhibitors were less likely to benefit.

A study is done to identify which subgroups of patients might have differential adherence to antiretroviral therapy (ART) in association with recent marijuana use. The result showed that adherence was positively associated with undetectable plasma virus and negatively associated with alcohol and other illicit drug use.

A comprehensive and up-to-date review of the treatment of patients coinfected with HIV and tuberculosis is provided. A scientific foundation for the devising management strategies for tuberculosis/HIV, in resource-poor settings, is discussed.