SummaryBackgroundRecurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing—which is more accurate than conventional typing used to date—to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.MethodsWe assessed patients from the REMoxTB trial—a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.FindingsWe assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0–6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.InterpretationWhole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.FundingWellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.

Retention in HIV medical care has been recognized as critical for long-term favorable clinical outcomes among HIV-positive patients. However, relatively little is known about specific factors related to HIV medical care adherence among HIV-positive women in rural areas in the United States, where the epidemic is rapidly growing among minorities and women. The objective of the current study was to assess barriers and facilitators to HIV clinic visit adherence among HIV-positive women in the rural southeastern region of the United States. Forty HIV-positive women were recruited from four outpatient clinics providing services to HIV-positive patients residing in 23 predominately rural counties in Alabama. Four focus groups were conducted ranging from 5 to 16 participants each. Content analysis was used to analyze and interpret the data. Data coding and sorting was conducted using QRS NVivo 8 software. Participants were predominately African American (92.3%) ranging in age from 29 to 69 years (mean = 46.1 years). On average, participants reported living with HIV for 8.8 years. Factors that impacted participants' ability to maintain clinic visit appointments included personal, contextual, and community/environmental factors that included: patient/provider relationships, family support, access to transportation, organizational infrastructure of the health care facility visited and perceived HIV stigma within their communities. The current study highlights the myriad of retention-in-care barriers faced by HIV-positive women living in rural areas in the southeastern United States. Innovative multilevel interventions that address these factors are sorely needed to increase long-term retention-in-care among HIV-positive women residing in rural areas.

A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro, 98% (n ‫؍‬ 96) of sputum samples with a known number of bacilli (10 7 to 10 2 bacilli) could be enumerated within 0.5 log 10 . In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log 10 (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml ؊1 sputum at day 0 (linear regression, P ‫؍‬ 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log 10 increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).