Proviral location affects cognate peptide-induced virus production and immune recognition of HIV-1-infected T cell clones.

BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that proviruses in specific chromosomal locations can evade immune surveillance. However, direct evidence of this mechanism is missing.METHODSIn this case report, we characterized integration sites and full genome sequences of expanded T cell clones in an EC before and after chemoradiation. We identified the cognate peptide of infected clones to investigate cell proliferation and virus production induced by T cell activation, and susceptibility to autologous CD8+ T cells.RESULTSThe proviral landscape was dominated by 2 large clones with replication-competent proviruses integrated into zinc finger (ZNF) genes (ZNF470 and ZNF721) in locations previously associated with deeper latency. A third nearly intact provirus, with a stop codon in Pol, was integrated into an intergenic site. Upon stimulation with cognate Gag peptides, infected clones proliferated extensively and produced virus, but the provirus in ZNF721 was 200-fold less inducible. While autologous CD8+ T cells decreased the proliferation of cells carrying the intergenic provirus, they had no effect on cells with the provirus in the ZNF721 gene.CONCLUSIONSWe provide direct evidence that upon activation of infected clones by cognate antigen, the lower inducibility of intact proviruses in ZNF genes can result in immune evasion and persistence.FUNDINGOffice of the NIH Director and National Institute of Dental & Craniofacial Research; NIAID, NIH; Johns Hopkins University Center for AIDS Research.

Implementation of Baltimore City's COVID-19 Isolation Hotel.

In May 2020, Baltimore City, Maryland, implemented the Lord Baltimore Triage, Respite, and Isolation Center (LBTC), a multiagency COVID-19 isolation and quarantine site tailored for people experiencing homelessness. In the first year, 2020 individuals were served, 78% completed isolation at LBTC, and 6% were transferred to a hospital. Successful isolation can mitigate outbreaks in shelters and residential recovery programs, and planning for sustainable isolation services integrated within these settings is critical as the COVID-19 pandemic continues. (Am J Public Health. 2022;112(6):876-880. https://doi.org/10.2105/AJPH.2022.306778).

Public Health Clinic-Based Hepatitis C Treatment.

INTRODUCTION: The availability of safe, effective treatments for hepatitis C virus infection has led to a call for the elimination of hepatitis C, but barriers to care persist. METHODS: In July 2015, the Baltimore City Health Department sexual health clinics began on-site hepatitis C virus treatment. Investigators conducted a retrospective evaluation of the first 2.5 years of this program. Data were extracted from the medical record through June 2019, and data analysis was completed in September 2019. RESULTS: Between July 2015 and December 2017, a total of 560 patients infected with hepatitis C virus accessed care at the Baltimore City Health Department sexual health clinics. Of these patients, 423 (75.5%) were scheduled for hepatitis C virus evaluation at the clinics, 347 (62.0%) attended their evaluation appointment, 266 (47.5%) were prescribed treatment, 227 (40.5%) initiated treatment, and 199 (35.5%) achieved sustained virologic response. Older age was independently associated with hepatitis C virus evaluation appointment attendance (aged 40-59 years: AOR=3.64, 95% CI=1.88, 7.06; aged ≥60 years: AOR=5.61, 95% CI=2.58, 12.21) compared with those aged 20-39 years. Among those who attended hepatitis C virus evaluation appointments, advanced liver disease was independently and positively associated with treatment initiation (AOR=11.89, 95% CI=6.35, 22.25). Conversely, illicit substance use in the past 12 months was negatively associated with hepatitis C virus treatment initiation (AOR=0.49, 95% CI=0.25, 0.96). CONCLUSIONS: The integration of hepatitis C virus testing and on-site treatment in public sexual health clinics is an innovative approach to improve access to hepatitis C virus treatment for medically underserved populations.

Effect of timing of first postnatal care home visit on neonatal mortality in Bangladesh: a observational cohort study.

OBJECTIVE: To assess the effect of the timing of first postnatal home visit by community health workers on neonatal mortality. DESIGN: Analysis of prospectively collected data using time varying discrete hazard models to estimate hazard ratios for neonatal mortality according to day of first postnatal home visit. DATA SOURCE: Data from a community based trial of neonatal care interventions conducted in Bangladesh during 2004-5. MAIN OUTCOME MEASURE: Neonatal mortality. RESULTS: 9211 live births were included. Among infants who survived the first day of life, neonatal mortality was 67% lower in those who received a visit on day one than in those who received no visit (adjusted hazard ratio 0.33, 95% confidence interval 0.23 to 0.46; P<0.001). For those infants who survived the first two days of life, receiving the first visit on the second day was associated with a 64% lower neonatal mortality than in those who did not receive a visit (adjusted hazard ratio 0.36, 0.23 to 0.55; P<0.001). First visits on any day after the second day of life were not associated with reduced mortality. CONCLUSIONS: In developing countries, especially where home delivery with unskilled attendants is common, postnatal home visits within the first two days of life by trained community health workers can significantly reduce neonatal mortality.

Impact of an integrated nutrition and health programme on neonatal mortality in rural northern India.

OBJECTIVE: To assess the impact of the newborn health component of a large-scale community-based integrated nutrition and health programme. METHODS: Using a quasi-experimental design, we evaluated a programme facilitated by a nongovernmental organization that was implemented by the Indian government within existing infrastructure in two rural districts of Uttar Pradesh, northern India. Mothers who had given birth in the 2 years preceding the surveys were interviewed during the baseline (n = 14 952) and endline (n = 13 826) surveys. The primary outcome measure was reduction of neonatal mortality. FINDINGS: In the intervention district, the frequency of home visits by community-based workers increased during both antenatal (from 16% to 56%) and postnatal (from 3% to 39%) periods, as did frequency of maternal and newborn care practices. In the comparison district, no improvement in home visits was observed and the only notable behaviour change was that women had saved money for emergency medical treatment. Neonatal mortality rates remained unchanged in both districts when only an antenatal visit was received. However, neonates who received a postnatal home visit within 28 days of birth had 34% lower neonatal mortality (35.7 deaths per 1000 live births, 95% confidence interval, CI: 29.2-42.1) than those who received no postnatal visit (53.8 deaths per 1000 live births, 95% CI: 48.9-58.8), after adjusting for sociodemographic variables. Three-quarters of the mortality reduction was seen in those who were visited within the first 3 days after birth. The effect on mortality remained statistically significant when excluding babies who died on the day of birth. CONCLUSION: The limited programme coverage did not enable an effect on neonatal mortality to be observed at the population level. A reduction in neonatal mortality rates in those receiving postnatal home visits shows potential for the programme to have an effect on neonatal deaths.

NGO facilitation of a government community-based maternal and neonatal health programme in rural India: improvements in equity.

Socio-economic disparities in health have been well documented around the world. This study examines whether NGO facilitation of the government's community-based health programme improved the equity of maternal and newborn health in rural Uttar Pradesh, India. A quasi-experimental study design included one intervention district and one comparison district of rural Uttar Pradesh. A household survey conducted between January and June 2003 established baseline rates of programme coverage, maternal and newborn care practices, and health care utilization during 2001-02. An endline household survey was conducted after 30 months of programme implementation between January and March 2006 to measure the same indicators during 2004-05. The changes in the indicators from baseline to endline in the intervention and comparison districts were calculated by socio-economic quintiles, and concentration indices were constructed to measure the equity of programme indicators. The equity of programme coverage and antenatal and newborn care practices improved from baseline to endline in the intervention district while showing little change in the comparison district. Equity in health care utilization for mothers and newborns also showed some improvements in the intervention district, but notable socio-economic differentials remained, with the poor demonstrating less ability to access health services. NGO facilitation of government programmes is a feasible strategy to improve equity of maternal and neonatal health programmes. Improvements in equity were most pronounced for household practices, and inequities were still apparent in health care utilization. Furthermore, overall programme coverage remained low, limiting the ability to address equity. Programmes need to identify and address barriers to universal coverage and care utilization, particularly in the poorest segments of the population.