American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

No abstract

This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.

Asymmetric localization is key to the proper function of certain prokaryotic proteins important to virulence, chemotaxis, cell division, development, motility, and adhesion. Shigella IcsA is localized to the old pole of the bacterium, where it mediates assembly of an actin tail inside infected mammalian cells. IcsA (VirG) is essential to Shigella intracellular motility and virulence. We used translational fusions between portions of IcsA and the green fluorescent protein (GFP) to determine the regions of IcsA that are necessary and sufficient for its targeting to the bacterial old pole. An IcsA-GFP fusion that lacks a signal peptide localized to the old pole, indicating that signal peptide-mediated secretion is not required for polar localization. Two regions within IcsA were required for localization of an IcsA-GFP fusion to the old pole. Further characterization of these regions indicated that amino acids 1-104 and 507-620 were each independently sufficient for polar localization. Finally, when expressed in Escherichia coli, Salmonella typhimurium, Yersinia pseudotuberculosis, and Vibrio cholerae, each of the two targeting regions localized to the pole, indicating that the mechanism of polar targeting used by IcsA is present generally among Enterobacteriacae and Vibrio.

BackgroundGlobal HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identifiedworldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015. MethodsWe assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data was collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses conducted for four time periods (1990-99, 2000-04, 2005-09 and 2010-15). The distribution of circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, number CRD42017067164.

We previously reported antiretroviral therapy (ART) outcomes of adults with AIDS in Haiti with 87% survival at one year. 1 We now report the 5-year outcomes of these 910 consecutive patients ≥ 13 years of age who initiated ART according to World Health Organization (WHO) guidelines between March

BackgroundSince HIV-1 RNA (viral load) testing is not routinely available in Haiti, HIV-infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Data on survival and treatment outcomes for HIV-1 infected patients who meet criteria for ART failure are limited. We conducted a retrospective study to compare survival rates for patients who experienced failure on first-line ART by clinical and/or immunologic criteria and switched to second-line ART vs. those who failed but did not switch.MethodsPatients receiving first-line ART at the GHESKIO Center in Port-au-Prince, Haiti, who met WHO clinical and immunologic criteria for failure were identified. Survival and treatment outcomes were compared in patients who switched their ART regimen and those who did not. Cox regression analysis was used to determine predictors of mortality after failure of first-line ART.ResultsOf 3126 patients who initiated ART at the GHESKIO Center between 1 March 2003 and 31 July 2008, 482 (15%) met WHO immunologic and/or clinical criteria for failure. Among those, 195 (41%) switched to second-line ART and 287 (59%) did not. According to Kaplan–Meier survival analysis, the probability of survival to 12 months after failure of first-line ART was 93% for patients who switched to second-line ART after failure and 88% for patients who did not switch. Predictors of mortality after failure of first-line ART were weight in the lowest quartile for sex, CD4 T cell count ≤ 100, adherence < 90% at the time of failure and not switching to second-line ART.ConclusionsPatients who failed first-line ART based on clinical and/or immunologic criteria and did not switch to second-line therapy faced a higher mortality than those who switched after failure. To decrease mortality, interventions to identify patients in whom ART may be failing earlier are needed urgently. In addition, there is a major need to optimize second-line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients.

IntroductionViral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti.MethodsPlasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures.ResultsData were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74–0.0.86), 23 to 35 months on ART (aOR:0.72[0.54–0.96]), baseline CD4 counts of 201–500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62–0.95] and 0.80 [0.66–0.98], respectively), poor adherence (aOR: 0.69 [0.59–0.81]), and TB co-infection (aOR: 0.73 [0.55–0.97]).ConclusionsThis study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.