The pharmacodynamics of an antimicrobial drug relates its pharmacokinetics to the time course of the antimicrobial effects at the site of the infection. Knowledge of the drug's antimicrobial pharmacodynamic effects (eg, rate and extent of bactericidal action and postantibiotic effect) provides a more rational basis for determination of optimal dosing regimens in terms of the dose and the dosing interval than do the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) determined in vitro. This article reviews pharmacokinetics, antimicrobial pharmacodynamics, the effect of pharmacodynamics on the emergence of resistant bacterial subpopulations, and the development of pharmacodynamic breakpoints for use in the design of trials of these drugs and in the treatment of infected patients.

Herbaspirillum species are not known to be human pathogens. We report on the identification of Herbaspirillum from cultures from 28 persons with cystic fibrosis (CF). Most isolates were initially identified as members of the Burkholderia cepacia complex. Although the role that these species play in lung disease in persons with CF is not known, their differentiation from other species is important and has serious implications for clinical care and patient well-being.

Background We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings HIV-infected patients ≥15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

Latino immigrants in the United States are disproportionately affected by HIV. Barriers to consistent attendance (retention) in HIV primary care constrain opportunities for HIV treatment success, but have not been specifically assessed in this population. We conducted semistructured interviews with 37 HIV-infected Latinos (aged ≥18 years and born in Puerto Rico or a Latin American Spanish-speaking country) and 14 HIV providers in metropolitan Boston (total n = 51). The Andersen Model of Healthcare Utilization informed a semistructured interview guide, which bilingual research staff used to explore barriers to HIV care. We used thematic analysis to explore the processes of retention in care. Six ubiquitous themes were perceived to influence HIV clinic attendance: (1) stigma as a barrier to HIV serostatus disclosure; (2) social support as a safety net during negative life circumstances; (3) unaddressed trauma and substance use leading to interruption in care; (4) a trusting relationship between patient and provider motivating HIV clinic attendance; (5) basic unmet needs competing with the perceived value of HIV care; and (6) religion providing a source of hope and optimism. Cultural subthemes were the centrality of family (familismo), masculinity (machismo), and trusting relationships (confianza). The timing of barriers was acute (e.g., eviction) and chronic (e.g., family conflict). These co-occurring and dynamic constellation of factors affected HIV primary care attendance over time. HIV-infected Latino immigrants and migrants experienced significant challenges that led to interruptions in HIV care. Anticipatory guidance to prepare for these setbacks may improve retention in HIV care in this population.

Antiretroviral therapy for treatment of HIV infection has become increasingly effective. Persistent poor HIV outcomes in racial and ethnic minority populations in the US call for a closer examination into why Latinos are at significant risk for acquiring and dying from HIV. To improve clinical outcomes and achieve an AIDS-free generation, HIV research must address disparities in HIV outcomes in Latinos, the largest ethnic/racial minority population in the US. Immigrant status as well as cultural factors influence HIV care utilization and are essential to highlight for effective intervention development in Latinos. A better understanding of these individual and contextual factors is critical to developing tailored approaches to engaging Latinos in HIV care. Based on a comprehensive literature review, we offer a framework for understanding what is needed from clinical practice and research to improve engagement in HIV care for US-based Latinos. These findings may have implications for other minority populations.

Background More patients in resource-limited settings are starting 2nd-line ART following 1st-line ART failure. We aimed to describe predictors of lack of virologic suppression in HIV-infected patients on 2nd-line ART in a roll-out program in South Africa. Methods Retrospective analysis was performed on an adult HIV treatment cohort who started 2nd-line ART (lopinavir/ritonavir, didanosine, and zidovudine) after virologic failure of 1st-line ART (2 consecutive HIV RNA >1000 copies/ml). Predictors of week-24 lack of suppression (HIV RNA > 400 copies/ml) on 2nd-line ART were determined by bivariate analysis where missing equals failure. A multivariable model adjusted for gender, age, and time to ART switch. We tested these findings in sensitivity analyses defining lack of suppression at week-24 as HIV RNA > 1000 and > 5000 copies/ml. Results Of 6,339 patients on ART, 202 started 2nd-line ART. At week-24 an estimated 41% (95% CI 34–47%) did not achieve virologic suppression. Female sex (adjusted OR=2.25; 95% CI, 1.03–4.88) and time to ART switch, (adjusted OR=1.07; 95% CI, 1.01–1.14 for each additional month) increased the risk of lack of virologic suppression. Age, CD4 count, and HIV RNA at 2nd-line ART initiation did not predict this outcome. In multivariate models, these findings were insensitive to the definition of lack of virologic suppression. Conclusions A substantial number of HIV-infected patients do not achieve virologic suppression by week-24 of 2nd-line ART. Women and patients with delayed start of 2nd-line ART after 1st-line ART failure were at an increased risk of lack of virologic suppression.

We examined HIV-1 resistance in children failing first-and second-line antiretroviral therapy (ART) in South Africa, all with clade C virus. Those exposed to full-dose ritonavir had multiple protease resistance mutations. Nineteen percent had wild type virus. Appropriate ART sequencing in sub-Saharan African children is essential for prolong treatment options.

Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results.