Epidemiology of HIV among US Air Force Military Personnel, 1996–2011

ObjectiveThe objectives of this study were to describe the epidemiology of HIV in the United States Air Force (USAF) from 1996 through 2011 and to assess whether socio-demographic characteristics and service-related mobility, including military deployments, were associated with HIV infection.MethodsWe conducted a retrospective cohort analysis of USAF personnel who were HIV-infected during the study period January 1, 1996 through December 31, 2011 and a matched case-control study. Cases were USAF personnel newly-diagnosed with HIV during the study period. Five randomly-selected HIV-uninfected controls were matched to each case by age, length of service, sex, race, service, component, and HIV test collection date. Socio-demographic and service-related mobility factors and HIV diagnosis were assessed using conditional logistic regression.ResultsDuring the study period, the USAF had 541 newly diagnosed HIV-infected cases. HIV incidence rate (per 100,000 person-years) among 473 active duty members was highest in 2007 (16.78), among black/ African-American USAF members (26.60) and those aged 25 to 29 years (10.84). In unadjusted analysis restricted to personnel on active duty, 10 characteristics were identified and considered for final multivariate analysis. Of these single (adjusted odds ratio [aOR], 8.15, 95% confidence interval [CI] 5.71–11.6) or other marital status (aOR 4.60, 95% CI 2.72–7.75), communications/ intelligence (aOR 2.57, 95% CI 1.84–3.60) or healthcare (aOR 2.07, 95% CI 1.28–3.35) occupations, and having no deployment in the past 2 years before diagnosis (aOR 2.02, 95% CI 1.47–2.78) conferred higher odds of HIV infection in adjusted analysis.ConclusionThe highest risk of HIV infection in the USAF was among young unmarried deployment-naïve males, especially those in higher risk occupation groups. In an era when worldwide military operations have increased, these analyses identified potential areas where targeted HIV prevention efforts may be beneficial in reducing HIV incidence in the USAF military population.     

Causes of Death among AIDS Patients after Introduction of Free Combination Antiretroviral Therapy (cART) in Three Chinese Provinces, 2010–2011

Introduction

Although AIDS-related deaths have had significant economic and social impact following an increased disease burden internationally, few studies have evaluated the cause of AIDS-related deaths among patients with AIDS on combination anti-retroviral therapy (cART) in China. This study examines the causes of death among AIDS-patients in China and uses a methodology to increase data accuracy compared to the previous studies on AIDS-related mortality in China, that have taken the reported cause of death in the National HIV Registry at face-value.

Methods

Death certificates/medical records were examined and a cross-sectional survey was conducted in three provinces to verify the causes of death among AIDS patients who died between January 1, 2010 and June 30, 2011. Chi-square analysis was conducted to examine the categorical variables by causes of death and by ART status. Univariate and multivariate logistic regression were used to evaluate factors associated with AIDS-related death versus non-AIDS related death.

Results

This study used a sample of 1,109 subjects. The average age at death was 44.5 years. AIDS-related deaths were significantly higher than non-AIDS and injury-related deaths. In the sample, 41.9% (465/1109) were deceased within a year of HIV diagnosis and 52.7% (584/1109) of the deceased AIDS patients were not on cART. For AIDS-related deaths (n = 798), statistically significant factors included CD4 count <200 cells/mm³ at the time of cART initiation (AOR 1.94, 95%CI 1.24–3.05), ART naïve (AOR 1.69, 95%CI 1.09–2.61; p = 0.019) and age <39 years (AOR 2.96, 95%CI 1.77–4.96).

Conclusion

For the AIDS patients that were deceased, only those who initiated cART while at a CD4 count ≥200 cells/mm3 were less likely to die from AIDS-related causes compared to those who didn’t initiate ART at all.     

Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China’s HIV/HCV Epidemics

Background

The human immunodeficiency virus 1 (HIV-1) epidemic in China historically stemmed from intravenous drug users (IDUs) in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV)/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.

Methods

Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.

Results

Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293), 3a (21.8%, 64/293), 6n (14.0%, 41/293), 1b (10.6%, 31/293), 1a (8.2%, 24/293), 6a (5.1%, 15/293) and 6u (2.4%, 7/293). The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong) and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan) bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10⁻⁴ and 2.38×10⁻³ substitutions site^-1 year^-1) and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6), suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A) to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs)-naïve IDUs.

Conclusion

This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and evolution of HCV in IDUs and are valuable for developing HCV prevention and management strategies for this population.     

A Census Tract–Level Examination of Social Determinants of Health among Black/African American Men with Diagnosed HIV Infection, 2005–2009—17 US Areas

Background

HIV disproportionately affects black men in the United States: most diagnoses are for black gay, bisexual, and other men who have sex with men (collectively referred to as MSM). A better understanding of the social conditions in which black men live and work may better explain why HIV incidence and diagnosis rates are higher than expected in this population.

Methods

Using data from the National HIV Surveillance System and the US Census Bureau''s American Community Survey, we examined the relationships of HIV diagnosis rates and 5 census tract–level social determinants of health variables for 21,948 black MSM and non-MSM aged ≥15 years residing in 17 areas in the United States. We examined federal poverty status, marital status, education level, employment status, and vacancy status and computed rate ratios (RRs) and prevalence odds ratios (PORs), using logistic regression with zero-inflated negative binomial modeling.

Results

Among black MSM, HIV diagnosis rates decreased as poverty increased (RR: 0.54). At the time of HIV diagnosis, black MSM were less likely than black non-MSM to live in census tracts with a higher proportion below the poverty level (POR: 0.81) and with a higher proportion of vacant houses (POR: 0.86). In comparison, housing vacancy was positively associated with HIV diagnosis rates among black non-MSM (RR: 1.65). HIV diagnosis rates were higher for black MSM (RR: 2.75) and non-MSM (RR: 4.90) whose educational level was low. Rates were significantly lower for black MSM (RR: 0.06) and non-MSM (RR: 0.26) as the proportion unemployed and the proportion married increased.

Conclusions

This exploratory study found differences in the patterns of HIV diagnosis rates for black MSM and non-MSM and provides insight into the transmission of HIV infection in areas that reflect substantial disadvantage in education, housing, employment, and income.     

Survival among Patients with HIV Infection and Smear-Negative Pulmonary Tuberculosis - United States, 1993–2006

Background

In patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression.

Methods

We analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993–2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006.

Results

Among 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86–0.93) and in those who were homeless (PR: 0.92, CI: 0.87–0.97) or used alcohol excessively (PR: 0.91, CI: 0.87–0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13–1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75–0.90) and after (HR: 0.81, CI: 0.71–0.92) the introduction of combination anti-retroviral therapy.

Conclusions

In the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality.     

HIV Infection and Awareness among Men Who Have Sex with Men–20 Cities,United States, 2008 and 2011

Over half of HIV infections in the United States occur among men who have sex with men (MSM). Awareness of infection is a necessary precursor to antiretroviral treatment and risk reduction among HIV-infected persons. We report data on prevalence and awareness of HIV infection among MSM in 2008 and 2011, using data from 20 cities participating in the 2008 and 2011 National HIV Behavioral Surveillance System (NHBS) among MSM. Venue-based, time-space sampling was used to recruit men for interview and HIV testing. We analyzed data for men who reported ≥1 male sex partner in the past 12 months. Participants who tested positive were considered to be aware of their infection if they reported a prior positive HIV test. We used multivariable analysis to examine differences between results from 2011 vs. 2008. HIV prevalence was 19% in 2008 and 18% in 2011 (p = 0.14). In both years, HIV prevalence was highest among older age groups, blacks, and men with lower education and income. In multivariable analysis, HIV prevalence did not change significantly from 2008 to 2011 overall (p = 0.51) or in any age or racial/ethnic category (p>0.15 in each category). Among those testing positive, a greater proportion was aware of their infection in 2011 (66%) than in 2008 (56%) (p<0.001). In both years, HIV awareness was higher for older age groups, whites, and men with higher education and income. In multivariable analysis, HIV awareness increased from 2008 to 2011 overall (p<0.001) and for all age and racial/ethnic categories (p<0.01 in each category). In both years, black MSM had the highest HIV prevalence and the lowest awareness among racial/ethnic groups. These findings suggest that HIV-positive MSM are increasingly aware of their infections.     

Head and neck squamous cell carcinomas among males of the three largest Asian diasporas in the US, 2004–2013

BackgroundHead and neck squamous cell carcinomas (HNSCC) have not been fully examined in the Asian diasporas in the US, despite certain Asian countries having the highest incidence of specific HNSCCs.MethodsNational Cancer Database was used to compare 1046 Chinese, 887 South Asian (Indian/Pakistani), and 499 Filipino males to 156,927 Non-Hispanic White (NHW) males diagnosed with HNSCC between 2004−2013. Multinomial logistic regression was used to assess the association of race/ethnicity with two outcomes – site group and late-stage diagnosis. Temporal trends were explored for site groups and subsites.ResultsSouth Asians had a greater proportion of oral cavity cancer [OCC] compared to NHWs (59 % vs. 25 %; OR_adj =7.3 (95 % CI: 5.9–9.0)). In contrast, Chinese (64 % vs. 9%; OR_adj =34.0 (95 % CI: 26.5–43.6)) and Filipinos (47 % vs. 9%; OR_adj =10.0 (95 % CI: 7.8–12.9)) had a greater proportion of non-oropharyngeal cancer compared to NHWs. All three Asian subgroups had a higher likelihood of being diagnosed by age 40 (14 % Chinese, 10 % South Asian and 8% Filipino compared to 3% in NHW; p < 0.001). Chinese males had lower odds of late-stage diagnosis, compared to NHWs. South Asian cases doubled from 2004 to 2013 largely due to an increase in OCC cases (34 cases in 2004 to 86 in 2013).ConclusionAsian diasporas are at a higher likelihood of specific HNSCCs. Risk factors, screening and survival need to be studied further, and policy changes are needed to promote screening and to discourage high-risk habits in these Asian subgroups.     

Pretreatment CD4 Cell Slope and Progression to AIDS or Death in HIV-Infected Patients Initiating Antiretroviral Therapy—The CASCADE Collaboration: A Collaboration of 23 Cohort Studies

Background

CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART.

Methods and Findings

We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46–81) cells/µl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97–1.04) for each 10 cells/µl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/µl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94–1.03, for each 10 cells/µl per year reduction in CD4 cell decline).

Conclusions

The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/µl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients.Please see later in the article for the Editors'' Summary     

HIV Status Disclosure to Sexual Partners,among People Living with HIV and AIDS on Antiretroviral Therapy at Sokodé Regional Hospital,Togo

BackgroundMany studies have reported factors associated with HIV status disclosure among People Living With HIV and AIDS (PLWHA) but very few were conducted among PLWHA receiving ART. In Togo, no study on HIV status disclosure to sexual partners has been conducted among PLWHA on ART yet. We sought to document factors associated with HIV status disclosure among PLWHA receiving ART at Sokodé regional hospital in Togo.MethodThis was a cross-sectional study conducted from May to July 2013 at the regional hospital of Sokodé among 291 PLWHA who had been on ART for at least three months.ResultsA total of 291 PLWHA on ART were enrolled in this study. Their mean age (±SD) was 37.3±9.3 years and the sex ratio (Male/Female) was 0.4. Among them, 215 (74.6%) completed the questionnaire on HIV sero-status disclosure. We found that 131 PLWHA (60.9%) had disclosed their HIV sero-status to their sexual partners; 130 (60.5%) were aware of the HIV status of their sexual partners. In the multivariate analysis, the factors associated with HIV status disclosure to sexual partners were: adherence to ART (aOR = 4.89; 95%CI = [1.52; 15.78]), sexual partner awareness of HIV sero-status (aOR = 52.73; 95%CI = [14.76; 188.36]) and marital status of PLWHA (aOR = 6.10; 95%CI = [1.74; 21.37]).ConclusionThis study allowed us to note that the disclosure of HIV status to sexual partners is relatively low and to document the associated factors such as adherence to ART, sexual partner awareness of HIV sero-status and marital status.     

HIV and Hepatitis C Mortality in Massachusetts, 2002–2011: Spatial Cluster and Trend Analysis of HIV and HCV Using Multiple Cause of Death

Background

Infectious diseases, while associated with a much smaller proportion of deaths than they were 50 years ago, still play a significant role in mortality across the state of Massachusetts. Most analysis of infectious disease mortality in the state only take into account the underlying cause of death, rather than contributing causes of death, which may not capture the full extent of mortality trends for infectious diseases such as HIV and the Hepatitis C virus (HCV).

Methods

In this study we sought to evaluate current trends in infectious disease mortality across the state using a multiple cause of death methodology. We performed a mortality trend analysis, identified spatial clusters of disease using a 5-step geoprocessing approach and examined spatial-temporal clustering trends in infectious disease mortality in Massachusetts from 2002–2011, with a focus on HIV/AIDS and HCV.

Results

Significant clusters of high infectious disease mortality in space and time throughout the state were detected through both spatial and space time cluster analysis. The most significant clusters occurred in Springfield, Worcester, South Boston, the Merrimack Valley, and New Bedford with other smaller clusters detected across the state. Multiple cause of death mortality rates were much higher than underlying cause mortality alone, and significant disparities existed across race and age groups.

Conclusions

We found that our multi-method analyses, which focused on contributing causes of death, were more robust than analyses that focused on underlying cause of death alone. Our results may be used to inform public health resource allocation for infectious disease prevention and treatment programs, provide novel insight into the current state of infectious disease mortality throughout the state, and benefited from approaches that may more accurately document mortality trends.     

Cost-Effectiveness of an Intervention to Reduce HIV/STI Incidence and Promote Condom Use among Female Sex Workers in the Mexico–US Border Region

Background

Previous research demonstrated efficacy of a brief behavioral intervention to reduce incidence of HIV and sexually transmitted infections (STIs) among female sex workers (FSWs) in Tijuana and Ciudad Juarez, Mexico, cities on Mexico''s border with the US. We assessed this intervention''s cost-effectiveness.

Methodology and Principal Findings

A life-time Markov model was developed to estimate HIV cases prevented, changes in quality-adjusted life expectancy (QALE), and costs per additional quality-adjusted life year gained (QALY), comparing (in US$2,009) no intervention to a once-only and annual intervention. Future costs and health benefits were discounted annually at 3%. Sensitivity analyses evaluated model robustness. We found that for a hypothetical 1,000 FSWs receiving the once-only intervention, there were 33 HIV cases prevented and 5.7 months of QALE gained compared to no intervention. The additional cost per QALY gained was US$183. For FSWs receiving the intervention annually, there were 29 additional HIV cases prevented and 4.5 additional months of QALE compared to the once-only intervention. The additional cost per QALY was US$1,075. When highly active antiretroviral therapy (HAART) was included in the model, the annual intervention strategy resulted in net savings and dominated both once-only and no intervention strategies, and remained robust across extensive sensitivity analyses. Even when considering clinical benefits from HAART, ignoring added costs, the cost per QALY gained remained below three times the Mexican GDP per capita, and below established cost-effectiveness thresholds.

Conclusions/Significance

This brief intervention was shown to be cost-effective among FSWs in two Mexico-US border cities and may have application for FSWs in other resource-limited settings.

Trial Registration

ClinicalTrials.gov {type:clinical-trial,attrs:{text:NCT00338845,term_id:NCT00338845}}NCT00338845     

Comparison of Projected and Actual Outcomes of the HIV/AIDS Epidemic in Malawi, 1990–2000

Background

In 1992 Liomba et al used HIV-AIDS prevalence data from 1980 to 1990 and projected the adult HIV prevalence and the impact of AIDS for the years 1991 to 2000, under high and low HIV incidence scenarios, using EpiModel, DemProj and the AIDS Impact Model. This report compares the actual outcomes of the HIV-AIDS epidemic in Malawi from 1991 to 2000 with projections made by Liomba et al.

Methods and Findings

Due to the lack of data on rural HIV prevalence in 1992, the prevalence estimates for the years 1980 to 1990 used by Liomba et al were higher than the now published prevalence. We re-estimated the projections for 1991 to 2000 based on more recent estimates of 1980 to 1990 HIV-AIDS prevalence using the Spectrum modeling software, and compared the old and new projections with the actual epidemic figures reported by NAC. The original projections made by Liomba et al and the adjusted projections made in this report are both very similar to the observed course of the AIDS epidemic reported by National AIDS Commission. Unfortunately for Malawi the epidemic seems to have followed the high scenario of HIV incidence.

Conclusion

The course of the epidemic in Malawi and the social and economic devastation caused by it, despite the presence of reasonably good projections and prevention recommendations by Liomba et al, highlights the need for better co-ordination between research and practice. It also emphasizes the need to examine the difficulties faced by countries like Malawi to act more rapidly and implement effective prevention measures in the face of an epidemic.     

Availability and Use of HIV Monitoring and Early Infant Diagnosis Technologies in WHO Member States in 2011–2013: Analysis of Annual Surveys at the Facility Level

BackgroundThe Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets have reinforced the importance of functioning laboratory services to ensure prompt diagnosis and to assess treatment efficacy. We surveyed the availability and utilization of technologies for HIV treatment monitoring and early infant diagnosis (EID) in World Health Organization (WHO) Member States.ConclusionThis is the first attempt to comprehensively gather information on HIV testing technology coverage in WHO Member States. The survey results suggest that major operational changes will need to be implemented, particularly in low- and middle-income countries, if the 90-90-90 targets are to be met.     

A period analysis of parity distribution among white and nonwhite women in the United States, 1940–1974

Abstract

The historical trends of childlessness and of one‐child, two‐child, and three‐or‐more‐child families among white and nonwhite women in the United States are studied in terms of period fertility tables. Given the age and parity of a woman, we can read from the fertility tables how her parity is expected to change at successive ages during the rest of her childbearing period, if she is subjected to the age‐parity‐specific fertility rates for a particular year. The fertility tables for white and nonwhite women are constructed for the years 1940, 19S0, 1960, 1970, and 1974. These tables show that among white women who have completed their childbearing (with period rates), the percentage with more than two children has decreased from 66 in 1960 to 27 in 1974, whereas the corresponding reduction among nonwhite women is from 67 to 48 per cent (Table 1, Case 1).     

The “ART” of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban,South Africa

Background

Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa.

Methodology/Principal Findings

We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived ≥10 kilometers from the testing center (RR = 1.37; 95% CI: 1.11–1.71), had a history of tuberculosis treatment (RR = 1.26; 95% CI: 1.00–1.58), or were referred for testing by a health care provider rather than self-referred (RR = 1.61; 95% CI: 1.22–2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors.

Conclusions/Significance

Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.     

Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001–2009

Background

U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.

Methods

We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU).

Results

Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95).

Conclusions

We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.     

Corticosteroid,catecholamine and glucose plasma levels in rabbits after repeated exposure to a novel environment or administration of (1–24)ACTH or insulin

The responsiveness of the adrenal cortex and the sympathoadrenal-medullary system to stress factors and administration of (1–24) ACTH and insulin was studied in adult rabbits. In comparison to untreated animals, exposure to a novel environment for 10 min followed by artery puncture on 6 consecutive days elicited a moderate increase of corticosteroid (C), norepinephrine (NE) and epinephrine (E) plasma levels. Intramuscular injection of 50 μg/kg body weight (1–24) ACTH increased C, NE and E plasma levels. Saline injection resulted in elevated NE levels; C, E and glucose remained unchanged. After injection of 1.0 IU/kg body weight insulin C levels were higher than those found after exposure to a novel environment for 10mmin followed by artery puncture; similarly, NE and E were increased.In accordance with results obtained in the rat or mouse the sympathoadrenal-medullary system in the rabbit is stimulated by stress factors such as handling, artery puncture or injection of (1–24) ACTH or insulin. In contrast the adrenal cortex can be stimulated only to a certain extent by these manipulations. An increased activation of adrenal cortex cells occurs only after insulin, a maximum stimulation only after (1–24) ACTH administration.     

Non-Aggregating Amylin Fragments as an Inhibitors of the Aggregation Process of Susceptible to Aggregation Fragments 18–22, 23–27, and 33–37 of Hormone

Amylin aggregation is one of the factors in the development of diabetes mellitus, which is classified as a civilization disease. The aim of this research was to find whether non-aggregating fragments 1–7, 8–12, 13–17 and 28–32 of amylin would inhibit the aggregation of the amyloidogenic cores 18–22, 23–27, 33–37 of hormone. In the study of the inhibitory potential of non-aggregating amylin fragments, a set of independent methods were used to study aggregation properties (spectroscopic and fluorescence studies with the use of indicators, microscopic studies, circular dichroism studies) and the method of prediction of aggregation properties. The performed research allowed to select the cyclic fragment (1–7) H-KCNTATC-OH with disulfide bond as an inhibitor capable of inhibiting the aggregation of all amyloidogenic cores 18–22, 23–27, 33–37 of the hormone. Additionally, it was found that this peptide inhibits insulin hot spot aggregation, which may indicate its universal utility in inhibiting the process of aggregation of hormones regulating carbohydrate metabolism directly related to the development of diabetes. Research on the possibility of the extensive use of the cyclic fragment (1–7) of H-KCNTATC-OH as a peptide inhibitor of the polypeptide/protein aggregation process is ongoing.     

HCV Genotypes,Characterization of Mutations Conferring Drug Resistance to Protease Inhibitors,and Risk Factors among Blood Donors in S?o Paulo,Brazil

Background

Hepatitis C virus (HCV) infection is a global health problem estimated to affect almost 200 million people worldwide. The aim of this study is to analyze the subtypes and existence of variants resistant to protease inhibitors and their association with potential HCV risk factors among blood donors in Brazil.

Methods

Repeat anti-HCV reactive blood donors are systematically asked to return for retest, notification, and counseling in which they are interviewed for risk factors for transfusion-transmitted diseases. We analyzed 202 donors who returned for counseling from 2007 to 2010 and presented enzyme immunoassay- and immunoblot-reactive results. The HCV genotypes and resistance mutation analyses were determined by the direct sequencing of the NS5b and NS3 regions, respectively. The HCV viral load was determined using an in-house real-time PCR assay targeting the 5′-NCR.

Results

HCV subtypes 1b, 1a, and 3a were found in 45.5%, 32.0%, and 18.0% of the donors, respectively. The mean viral load of genotype 1 was significantly higher than that of the genotype 3 isolates. Subtype 1a was more frequent among young donors and 3a was more frequent among older donors. Protease inhibitor-resistant variants were detected in 12.8% of the sequenced samples belonging to genotype 1, and a higher frequency was observed among subtype 1a (20%) in comparison to 1b (8%). There was no difference in the prevalence of HCV risk factors among the genotypes or drug-resistant variants.

Conclusions

We found a predominance of subtype 1b, with an increase in the frequency of subtype 1a, in young subjects. Mutations conferring resistance to NS3 inhibitors were frequent in treatment-naïve blood donors, particularly those infected with subtype 1a. These variants were detected in the major viral population of HCV quasispecies, have replicative capacities comparable to nonresistant strains, and could be important for predicting the response to antiviral triple therapy.