Publications

OBJECTIVES

HIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants.

METHODS

Near-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naïve individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7.5 years. Subtypes were inferred by Los Alamos Recombinant Identification Program (RIP) 3.0 and compared with Sanger/REGA and MiSeq/RIP. 'Nonrecombinants' and 'recombinants' infections were compared in terms of pretherapy viral load, CD4 cell count, posttherapy time to virologic suppression, virologic rebound, first CD4 rise above baseline and sustained CD4 recovery.

RESULTS

Prevalence of intersubtype recombinants varied depending on the genomic region examined: gag (15%), prrt (11%), int (8%), vif (10%), vpr (2%), vpu (9%), GP120 (8%), GP41 (18%), and nef (4%). Of the 200 patients with near-full-genome data, prevalence of intersubtype recombination was 46%; the most frequently observed recombinant was A1-D (25%). Sanger/REGA and MiSeq/RIP yielded generally consistent results. Phylogenetic tree revealed most recombinants did not share common ancestors. No temporal trend was observed (all P > 0.1). Subsequent subtype switches were detected in 27 of 143 (19%) study participants with follow-up sequences. Nonrecombinant versus recombinants infections were not significantly different in any pre nor posttherapy clinical correlates examined (all P > 0.2).

CONCLUSION

Intersubtype recombination was highly prevalent (46%) in Uganda if the entire HIV genome was considered, but was neither associated with clinical correlates nor therapy outcomes.

Hepatitis C virus (HCV) is one of the most prevalent causes of chronic blood-borne infections worldwide. Despite developments of highly effective treatments, most infected individuals are unaware of their infection. Approximately 75% of infections are in low- and middle-income countries; therefore, continuing research in HCV molecular virology and the development of vaccines and affordable diagnostics is required to reduce the global burden. Various intracellular forms of the HCV nucleocapsid (core) protein are produced in cell culture; these comprise the conventional p21 core and the newly discovered shorter isoforms (minicores). Minicores lack the N-terminus of p21 core. This study was conducted to determine if minicores are secreted in cell culture and more importantly if they circulate in the blood of individuals infected with HCV. We also developed a new monoclonal antibody that detects minicores targeting a C-terminal region common to p21 core and minicores. Direct evidence of minicores requires western blot analysis to distinguish the detection of p21 core from minicores. However, the sensitivity for western blot detection of HCV proteins from blood is nil without their prior purification/enrichment from blood. Therefore, we developed a purification method based on a heparin/Mn precipitation of apolipoprotein B-containing lipoproteins because HCV is thought to circulate as a hybrid lipoviral particle. Minicores are secreted in culture when cells are grown in the presence of human serum. The heparin/Mn precipitate from HCV-infected cell culture supernatants and from the blood of 4 patients with high-titer genotype-1 HCV contained minicores. : Minicores are major newly discovered HCV proteins that are secreted and circulate in blood during natural infections. Minicore proteins have translational potential as targets in diagnostic assays and in vaccine development. ( 2018;2:21-28).

Despite over 28,000 reported cases of Ebola virus disease (EVD) in the 2013-16 outbreak in West Africa, we are only beginning to trace the complex biosocial processes that have promoted its spread. Important questions remain, including the effects on survivors of clinical sequelae, loss of family and livelihood, and other psychological and social trauma. Another poorly understood question is what effect social protection and job creation programs have had on survivors' wellbeing. Several clinical and social protection programs have been developed to respond to the needs of EVD survivors; however, little in the way of impact evaluation has taken place. We enrolled 200 randomly selected EVD survivors from Port Loko, Kenema, and Kailahun districts in Sierra Leone and stratified them based on the amount of instrumental social protection received post-discharge from an Ebola Treatment Unit. We then conducted a survey and in-depth interviews to assess participants' wellbeing and food security. Social protection categories II-IV (moderate to extensive) were each significantly associated with ∼15-22% higher wellbeing scores compared to minimal social protection (p < 0.001). Only social protection category IV (extensive) was significantly associated with being food secure (adjusted odds ratio 6.11; 95% confidence interval, 2.85-13.10) when compared to minimal social protection. Qualitative themes included having a sense of purpose during the crisis (work and fellowship helped survivors cope); using cash transfers to invest in business; the value of literacy and life-skills classes; loss of breadwinners (survivors with jobs were able to take over that role); and combating the consequences of stigma. We conclude that, for EVD survivors, short-term social protection during the vulnerable period post-discharge can pay dividends two years later. Based on the empiric evidence presented, we discuss how terms such as "outbreak" and "epidemic" do symbolic violence by creating the illusion that social suffering ends when transmission of a pathogen ceases.

OBJECTIVE

There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.

RESEARCH DESIGN AND METHODS

We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.

RESULTS

There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-cause mortality (HR 1.73, 95% CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.

CONCLUSIONS

Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.