The CDC recommends pharyngeal screening of Neisseria gonorrhoeae (GC) and rectal screening of GC and Chlamydia trachomatis (CT) in HIV-infected and at-risk men who have sex with men (MSM). There are currently no recommendations to routinely screen women at extragenital sites. We define the prevalence of extragenital GC and CT in women attending two urban STD clinics in Baltimore City and compare it to the prevalence of extragenital infections in MSM and men who have sex with women (MSW).
All patients who reported extragenital exposures in the preceding 3 months, who presented for care between 6/1/2011 and 5/31/2013, and were tested for GC and CT using nucleic acid amplification tests at all sites of exposure were included in the analyses. We used logistic regression models to identify risk factors for extragenital infections.
10,389 patients were included in this analysis (88% African American, mean age 29 years, 42% women, 7% MSM, 2.5% HIV infected). The prevalence estimates of any extragenital GC and CT were: 2.4% GC and 3.7% CT in women; 2.6% GC and 1.6% CT in MSW; 18.9% GC and 11.8% CT in MSM. Among women, 30.3% of GC infections and 13.8% of CT infections would have been missed with urogenital-only testing. Unlike MSM, age ≤ 18 years was the strongest predictor of extragenital infections in women.
Although the prevalence of extragenital gonorrhea and chlamydia is highest in MSM, a significant number of GC and CT infections in young women would be missed with genital-only testing. Cost-effectiveness analyses are needed to help inform national guidelines on extragenital screening in young women.
There is scant data on young children receiving protease inhibitor (PI)-based therapy in real-life resource-limited settings and on the optimal timing of therapy among children who survive infancy. Our aim was to evaluate outcomes at the Hospital del Niño, Panama, where children have been routinely treated with lopinavir/ritonavir (LPV/r)-based therapy since 2002.
Retrospective cohort analysis of all HIV-infected children enrolled in care between January 1, 1991 and June 1, 2011. Kaplan-Meier method and Cox proportional hazards regression were used to evaluate death, virologic suppression, and virologic rebound.
Of 399 children contributing 1,944 person-years of follow-up, 254 (63.7%) were treated with LPV/r and 94 (23.6%) were never treated with antiretrovirals (ARVs). Among infants, improved survival was associated with male gender (HRdeath 0.54, 95% CI 0.32–0.92) and treatment with highly active antiretroviral therapy (HAART) (HRdeath 0.32, 95% CI 0.12–0.83), while residence outside of Panama City was associated with poorer survival (HRdeath 1.72, 95% CI 1.01–2.94). Among children who survived to 1 year of age without exposure to ARVs, LPV/r-based therapy improved survival (HRdeath 0.07, 95% CI 0.01–0.33). Virologic suppression was achieved in 42.1%, 70.5%, and 85.1% by 12, 24 and 60 months of follow up among children treated with LPV/r. Virologic suppression was not associated with prior ARV exposure or age at initiation of therapy but was associated with residence outside of Panama City (HRsuppression 1.93, 95% CI 1.19–3.14). Patients with a baseline viral load > 100,000 copies/mL were less likely to achieve suppression (HRsuppression 0.37, 95% CI 0.21–0.66). No children who achieved virologic suppression after initiating LPV/r died.
LPV/r-based therapy improved survival not only in infants but also in children over 1 year of age. Age at initiation of LPV/r-based therapy or prior ARVs did not impact virologic outcomes.
Children; HIV-infection; mortality; virologic outcomes; Lopinavir/Ritonavir
Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA). In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (ΔlspA). Exposure of human peripheral blood mononuclear cells (PBMC) to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01), LprH (p<0.05), LprI (p<0.05), LprP (p<0.001), LprQ (p<0.005), MPT83 (p<0.005), or PhoS1 (p<0.05), resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with ΔlspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05). These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission.
Despite significant advancements in hepatitis C virus (HCV) treatments, the majority of individuals infected with HCV remain undiagnosed. We report on senior citizen center-based HCV testing in Baltimore, which revealed a 9.4% prevalence of infection. Our data suggest that community-based HCV testing and linkage to care in appropriate settings is feasible and high yield.
hepatitis C; linkage to care; senior citizen centers; testing
Latinos in the U.S. are disproportionately affected by HIV and are at risk for late presentation to care. Between June 2011 and January 2012, we conducted a cross-sectional survey of 209 Baltimore Latinos at community-based venues to evaluate the feasibility of using communication technology (ICT)-based interventions to improve access to HIV testing and education within the Spanish-speaking community in Baltimore. Participants had a median age of 33 years (IQR 28-42), 51.7% were male, and 95.7% were foreign-born. Approximately two-thirds (63.2%) had been in the U.S. less than 10 years and 70.1% had been previously tested for HIV. Cell phone (92.3%) and text messaging (74.2%) was used more than Internet (52.2%) or e-mail (42.8%) (p<0.01). In multivariate analysis, older age and lower education were associated with less utilization of Internet, e-mail and text messaging, but not cell phones. Interest was high for receiving health education (73.1%), HIV education (70.2%), and test results (68.8%) via text messaging. Innovative cell phone-based communication interventions have the potential to link Latino migrants to HIV prevention, testing and treatment services.
HIV; cellular phone; technology; Latino health; migrants
QuantiFERON-TB Gold In-Tube test (QFT-GIT) can be used as an alternative to tuberculin skin testing (TST) for the targeted testing of latent tuberculosis. Due to many shortcomings with TST, QFT-GIT usage is increasing. QFT-GIT implementation in the inpatient setting remains unclear.
We retrospectively identified patients admitted to a tertiary care academic center who received either a TST or a QFT-GIT in the 18 months prior to and after QFT-GIT implementation in March 2012. Risk factors associated with indeterminate results were evaluated.
The proportion of inpatients receiving a test for tuberculosis infection doubled following QFT-GIT implementation (1.4% vs 2.9%). After QFT-GIT became available, 75% of tested people received a QFT-GIT and 25% received a TST. We found indeterminate test results in 19.8%. Independent predictors of indeterminate results were female sex (adjusted odds ratio [AOR], 1.64), lymphopenia (AOR, 2.21), hypoalbuminemia (AOR, 6.81) and sample collection by nonphlebotomists (AOR, 3.0, vs phlebotomists). Of patients who had indeterminate results, 42% had a subsequent indeterminate result on repeat testing. All indeterminate results were due to a low mitogen response.
QFT-GIT testing in the inpatient setting is associated with a high proportion of indeterminate results that is associated with host factors and preanalytical errors. Careful selection of patients to be tested and training on sample processing for QFT-GIT testing should be considered to decrease indeterminate results.
IGRA; TB screening; TB diagnostics
In the US, HIV disproportionately affects Latinos who often present late in the disease. Baltimore has seen a recent rapid growth in its Latino population paralleled by an increasing impact of HIV/AIDS among Latinos. From 2009 to 2010, we performed a cross-sectional survey of Latinos accessing the Baltimore City Health Department (BCHD) Latino Outreach services to assess self-report of previous HIV testing, with particular attention to migration history and risk behaviors. Of 247 Latinos (46% male) accessing BCHD outreach services, 96% were foreign-born. Self-perceived HIV risk was not associated with actual risk behaviors or HIV testing. In multivariate models, previous HIV testing was correlated with knowledge of HIV transmission modes and knowing that a person with HIV can appear healthy. Consistent with CDC recommendations, HIV screening among Latino immigrants should not be limited to individuals with self-perceived risk for HIV. Promoting key pieces of HIV knowledge may improve HIV testing behaviors.
HIV/AIDS; Prevention; Hispanic; Latino; Condom; HIV knowledge; HIV testing
HIV/AIDS disproportionately affects Hispanics. Our objective was to determine the risk of late diagnosis and rate of survival after HIV/AIDS diagnosis among Hispanics compared to other racial/ethnic groups. We performed a systematic review of the PubMed database for peer-reviewed articles published between January 2000 and September 2010. Primary outcomes included survival after HIV/AIDS diagnosis and delayed diagnoses. The definition of delayed diagnosis varied by study, ranging from concurrent HIV/AIDS diagnosis to diagnosis of AIDS within 3 years of HIV diagnosis. We found that Hispanics are at significantly greater risk for delayed diagnosis than non-Hispanic whites. Hispanic males and foreign-born Hispanics had the highest risk of late diagnosis. Available data on survival were heterogeneous, with better outcomes in some Hispanic subgroups than in others. Survival after antiretroviral initiation was similar between Hispanics and Whites. These findings emphasize the need for culturally-sensitive strategies to promote timely diagnosis of HIV infection among Hispanics and to examine the health out-comes and needs of high risk Hispanic subgroups.
HIV; AIDS; Hispanic; Delayed diagnosis; Survival rate; Mortality
Since 2003, U.S. organizations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhea (NG) and Chlamydia (CT). Our objective was to determine whether wider testing resulting from these guidelines would produce an increase in NG/CT diagnoses.
We studied 3,283 patients receiving HIV care 1999–2007 in the Johns Hopkins Hospital HIV clinic. The two primary outcomes were: 1) the occurrence of any NG/CT testing in each year of care and 2) the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with NG/CT was defined as the number of patients with positive results divided by the number of patients in care. Trends were analyzed with repeated measures logistic regression.
The proportion of patients tested for NG/CT increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested, 1.17 [1.15, 1.19]). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67 [0.55, 0.81]). The proportion of all patients in care diagnosed with NG/CT therefore remained generally stable 1999–2007 (OR per year 0.97 [0.91, 1.04]).
Universal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with NG/CT. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high risk groups rather than universal screening may be warranted.
HIV prevention; health service research; Neisseria gonorrhoeae; Chlamydia trachomatis; screening; guidelines
Screening HIV-infected men for gonorrhea (GC) and Chlamydia (CT) may decrease HIV transmission and reduce the incidence of pelvic inflammatory disease in female partners. This study determined GC/CT testing rates in a clinical HIV cohort before and after 2003 when the U.S. Centers for Disease Control and Prevention issued guidelines for GC/CT screening.
First GC/CT testing episodes were identified for all men enrolling in a Baltimore HIV clinic 1999–2007. Multivariate Cox and logistic regression were used to assess clinical and demographic factors associated with being tested and with having a positive result.
Among 1110 men, the rate of GC/CT testing upon clinic enrollment increased from 4.0% prior to 2003 to 16.5% afterward, and the rate of ever being tested increased from 34.2% to 49.1% (P <0.001 for both comparisons). Among men with same sex contact, 10% of first testing episodes included extragenital sites. Among the 342 men ever-tested, 5.2% had positive results on first testing. Predictors of testing included enrolling after 2003, younger age, frequent visits, and black race. Predictors of a positive test result included CD4 count ≥200 cells/mm3 and younger age.
GC/CT testing rates among men increased substantially after the 2003 guidelines but remain low. Disseminating existing evidence for GC/CT screening and promoting operational interventions to facilitate it are warranted.
health service research; gonorrhea; Chlamydia; screening; HIV secondary prevention
Elite controllers or suppressors (ES) are a group of HIV-1-infected individuals who maintain viral loads below the limit of detection of commercial assays for many years. The mechanisms responsible for this remarkable control are under intense study, with the hope of developing therapeutic vaccines effective against HIV-1. In this study, we addressed the question of the intrinsic susceptibility of ES CD4+ T cells to infection. While we and others have previously shown that CD4+ T cells from ES can be infected by HIV-1 isolates in vitro, these studies were confounded by exogenous activation and in vitro culture of CD4+ T cells prior to infection. In order to avoid the changes in chemokine receptor expression that have been associated with such exogenous activation, we infected purified CD4+ T cells directly after isolation from the peripheral blood of ES, viremic patients, and uninfected donors. We utilized a green fluorescent protein (GFP)-expressing proviral construct pseudotyped with CCR5-tropic or CXCR4-tropic envelope to compare viral entry using a fluorescence resonance energy transfer-based, single-round virus-cell fusion assay. The frequency of productive infection was also compared by assessing GFP expression. CD4+ T cells from ES were as susceptible as or more susceptible than cells from viremic patients and uninfected donors to HIV-1 entry and productive infection. The results of this physiological study strongly suggest that differences in HIV-1 entry and infection of CD4+ T cells alone cannot explain the elite control of viral replication.
Many studies have evaluated factors influencing STD/HIV disparities between African-American and white populations, but fewer have explicitly included Latinos for comparison.
We analyzed demographic and behavioral data captured in electronic medical records of patients first seen by a clinician in one of two Baltimore City public STD clinics between 2004 and 2007. Records from white, African-American, and Latino patients were included in the analysis.
There were significant differences between Latinos and other racial/ethnic groups for several behavioral risk factors studied, with Latino patients reporting fewer behavioral risk factors than other patients. Latinos were more likely to have syphilis, but less likely to have gonorrhea than other racial/ethnic groups. English-proficient Latina (female) patients reported higher rates of infection and behavioral risk factors than Spanish-speaking Latina patients. After adjustment for gender and behavioral risk factors, Spanish-speaking Latinas also had significantly less risk of sexually transmitted infections than did English-speaking Latinas.
These results are consistent with other studies showing that acculturation (as measured by language proficiency) is associated with increases in reported sexual risk behaviors among Latinos. Future studies on sexual risk behavior among specific Latino populations characterized by country of origin, level of acculturation, and years in the U.S. may identify further risk factors and protective factors to guide development of culturally appropriate STD/HIV interventions.
Hispanic/Latino; sexually transmitted disease clinic; racial/ethnic disparities; acculturation; gonorrhea; chlamydia; syphilis; HIV
In the U.S. more than half of incident tuberculosis (TB) cases occur in immigrants. Current guidelines recommend screening and treatment for latent TB infection (LTBI) within 5 years of arrival to the U.S. This study evaluates the timing of LTBI therapy among immigrants presenting for care to a public health TB clinic.
Retrospective chart review of patients prescribed LTBI treatment based on medical records from Prince Georges County Health Department.
1882 immigrants received LTBI therapy at Prince Georges County Health Department between 1999 and 2004. 417 of these patients were diagnosed with LTBI through contact investigations and were excluded from the analysis. Among the remaining 1465 individuals, median time from arrival to the U.S. until initiation of LTBI therapy was 5 months (range 0–42.4 years). 16% of all immigrants initiated therapy more than 5 years after arrival to the U.S. A logistic regression model using risks identified on univariate analysis revealed that referral for therapy by non-immigration proceedings was the strongest predictor of initiation of therapy more than 5 years after arrival to the U.S. Other factors associated with > 5 year U.S. residence prior to initiation of LTBI therapy included female gender (adjusted odds ratio (AOR) 1.8, 95% CI 1.2–2.6), age ≥ 35 (AOR = 4.1, 95% 2.5–6.6), and originating from Latin American and the Caribbean (AOR = 1.9, 95% CI 1.3–3.0).
Foreign-born individuals who are not referred for LTBI therapy through immigration proceedings are less likely to receive LTBI therapy within 5 years of arrival to the U.S. These data highlight the need to explore other mechanisms for timely LTBI screening beyond services provided by immigration.
The ability of medical residents training at U.S. urban medical centers to diagnose and manage tuberculosis cases has important public health implications. We assessed medical resident knowledge about tuberculosis diagnosis and early management based on American Thoracic Society guidelines.
A 20-question tuberculosis knowledge survey was administered to 131 medical residents during a single routinely scheduled teaching conference at four different urban medical centers in Baltimore and Philadelphia. Survey questions were divided into 5 different subject categories. Data was collected pertaining to institution, year of residency training, and self-reported number of patients managed for tuberculosis within the previous year. The Kruskal-Wallis test was used to detect differences in median percent of questions answered correctly based on these variables.
The median percent of survey questions answered correctly for all participating residents was 55%. Medical resident knowledge about tuberculosis did not improve with increasing post-graduate year of training or greater number of patients managed for tuberculosis within the previous year. Common areas of knowledge deficiency included the diagnosis and management of latent tuberculosis infection (median percent correct, 40.7%), as well as the interpretation of negative acid-fast sputum smear samples.
Many medical residents lack adequate knowledge of recommended guidelines for the management of tuberculosis. Since experience during training influences future practice pattterns, education of medical residents on guidelines for detection and early management of tuberculosis may be important for future improvements in national tuberculosis control strategies.
Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-γ responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.