Factors Associated with Early Sexual Debut among Ghanaian Women from the Manya – Krobo District, – Ghana, 2011

Affiliation: Department of Epidemiology and Biostatistics GW, School of Public Health and Health Services Title: Factors associated with early sexual debut among Ghanaian women from the Manya – Krobo district, – Ghana, 2011 Background: The dipo, a Krobo puberty initiation rite practiced annually among an estimated 2,000 Ghanaian females ages 2–20, is a cultural rite of passage into womanhood that is intended to promote abstinence from sexual activity until marriage. Objectives: This study examined the risk of early sexual debut among dipo-initiated Krobo females versus uninitiated Krobo females. This study also assessed Manya–Krobo societal opinions regarding the sexual health outcomes of initiates and existing modifications of the rite. Methods: Mixed-methods. Utilizing a retrospective cohort study design, we surveyed 306 unwed Krobo females from Agormanya ages 13–20. We employed Cox proportional hazard regressions assessing the effects of model covariates upon sexual debut and age at sexual debut. Qualitative analysis included nine interviews conducted among Manya–Krobo district community members who either supported or opposed the dipo. Responses were analyzed using Dedoose QDA software to determine patterns in attitudes and opinions regarding initiates’ sexual behaviors and to identify current ceremonial changes. Results: Dipo initiated participants had a 1.8 increased hazard rate of early sexual debut as compared to uninitiated participants after adjusting for covariates, however, results were not statistically significant (aHR: 1.8, 95% C.I: 0.8–4.0). Qualitative data indicated that some dipo opponents stated participation promotes promiscuity and teen pregnancy while select supporters asserted the rite protects participants from these outcomes. Key ceremonial changes included a reduction in age eligibility and length of dipo preparatory period. Conclusions: These study findings do not offer conclusive evidence that participation in the dipo increases the risk of early sexual debut among initiated versus uninitiated Krobo females. Study findings suggest the reduction in age of dipo eligibility may increase the likelihood of sexual debut following the ceremony. Participants who received the rite as toddlers had a greater length of time between the dipo and adulthood to become sexually active post-initiation than females who were initiated during their late teens/early twenties

Prevalence and Trends in Transmitted and Acquired Antiretroviral Drug Resistance, Washington, DC, 1999-2014.

Background Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC. Methods We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309). Using logistic regression, we assessed associations between patient characteristics and transmitted resistance to any antiretroviral. Results Prevalence of TDR was 20.5%, of ADR 40.5%, and of CDR 45.1% in the respective analysis groups. From 2004 to 2013, TDR prevalence decreased for nucleoside and nucleotide analogue reverse transcriptase inhibitors (15.0 to 5.5%; p = 0.0003) and increased for integrase strand transfer inhibitors (INSTIs) (0.0–1.4%; p = 0.04). In multivariable analysis, TDR was not associated with age, race/ethnicity, HIV risk group, or years from HIV diagnosis. Conclusions In this urban cohort of HIV-infected persons, almost half of participants tested had evidence of CDR; and resistance to INSTIs was increasing. If this trend continues, inclusion of the integrase-encoding region in baseline genotype testing should be strongly considered

Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway.

Germline genes often become re-expressed in soma-derived human cancers as "cancer/testis antigens" (CTAs), and piRNA (PIWI-interacting RNA) pathway proteins are found among CTAs. However, whether and how the piRNA pathway contributes to oncogenesis in human neoplasms remain poorly understood. We found that oncogenic Ras combined with loss of the Hippo tumor suppressor pathway reactivates a primary piRNA pathway in Drosophila somatic cells coincident with oncogenic transformation. In these cells, Piwi becomes loaded with piRNAs derived from annotated generative loci, which are normally restricted to either the germline or the somatic follicle cells. Negating the pathway leads to increases in the expression of a wide variety of transposons and also altered expression of some protein-coding genes. This correlates with a reduction in the proliferation of the transformed cells in culture, suggesting that, at least in this context, the piRNA pathway may play a functional role in cancer.We thank the Cold Spring Harbor Laboratory Microscopy Shared Resources for assistance, which are funded in part by Cancer Center Support Grant 5P30CA045508. This work was supported in part by a grant from the STARR Cancer Consortium, grants from the National Institutes of Health (NIH MERIT Award, R37GM062534 to G. J.H.), and a generous gift from Kathryn W. Davis to G.J.H. N.P. and G.J.H. are or were Investigators of the Howard Hughes Medical Institute. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. Cell lines have been deposited by A.S. at the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1). G.J.H. is supported by Cancer Research UK and is a Wellcome Trust Investigator.This is the final version of the article. It first appeared from Cold Spring Harbor Press at http://dx.doi.org/10.1101/gad.284927.116

Interruptions of antiretroviral therapy in children and adolescents with HIV infection in clinical practice: a retrospective cohort study in the USA.

INTRODUCTION: Changes in combination antiretroviral therapy (cART) throughout childhood challenge the continuity of paediatric HIV treatment. This study aimed to evaluate the prevalence of treatment interruption (TI), including lamivudine (3TC) monotherapy, and the relationship of TI to virologic and immunologic parameters in HIV-infected paediatric patients. METHODS: Nested within a prospective observational study of a city-wide cohort of HIV-infected persons in the District of Columbia, this sub-study collected retrospective data on antiretroviral therapy, enrolment (endpoint) and historic (lifelong) CD4 counts and HIV RNA viral load (VL) of the paediatric cohort. TI was defined as interruption of cART ≥4 consecutive weeks. Data on TI, including 3TC monotherapy TI (MTI), were collected. Descriptive statistics and univariate testing were used to compare children with TI and MTI to children on continuous treatment (CT). RESULTS: Thirty-eight (28%) out of 136 enrolled children (median age=12.9 years) experienced TI, with 14 (37%) of those placed on 3TC MTI. Significantly lower endpoint median CD4 counts (598 cells/mm(3) vs. 815 cells/mm(3); p=0.003) and CD4% (27.5% vs. 33%; p=0.006) were observed in the TI cohort as compared to the CT cohort. The median endpoint VL in the overall TI cohort was ~4 times higher than among the CT cohort (1427 copies/mL vs. 5581 copies/mL; p CONCLUSIONS: In our study, we observed high frequency of the TI in HIV in paediatric HIV clinical practice. All TIs, including 3TC MTI, were associated with significantly lower endpoint median CD4 counts and higher median VLs, as compared to CT in paediatric patients. The high frequency of TI and associated poor outcomes suggest a need for a better strategy in managing the course of the paediatric and adolescent cART

Comparing Cost-Effectiveness of HIV Testing Strategies: Targeted and Routine Testing in Washington, DC.

BACKGROUND: Routine HIV testing is an essential approach to identifying undiagnosed infections, linking people to care and treatment, and preventing new infections. In Washington, DC, where HIV prevalence is 2.4%, a combination of routine and targeted testing approaches has been implemented since 2006. METHODS: We sought to evaluate the cost effectiveness of the District of Columbia (DC) Department of Health\u27s routine and targeted HIV testing implementation strategies. We collected HIV testing data from 3 types of DC Department of Health-funded testing sites (clinics, hospitals, and community-based organizations); collected testing and labor costs; and calculated effectiveness measures including cost per new diagnosis and cost per averted transmission. RESULTS: Compared to routine testing, targeted testing resulted in higher positivity rates (1.33% vs. 0.44%). Routine testing averted 34.30 transmissions per year compared to targeted testing at 17.78. The cost per new diagnosis was lower for targeted testing ($2,467 vs.$7,753 per new diagnosis) as was the cost per transmission averted ($33,160 vs.$104,205). When stratified by testing site, both testing approaches were most cost effective in averting new transmissions when conducted by community based organizations ($25,037 routine;$33,123 targeted) compared to hospitals or clinics. CONCLUSIONS: While routine testing identified more newly diagnosed infections and averted more infections than targeted testing, targeted testing is more cost effective per diagnosis and per transmission averted overall. Given the high HIV prevalence in DC, the DC Department of Health\u27s implementation strategy should continue to encourage routine testing implementation with emphasis on a combined testing strategy among community-based organizations

Improving HIV Surveillance Data for Public Health Action in Washington, DC: A Novel Multiorganizational Data-Sharing Method

Background: The National HIV/AIDS Strategy calls for active surveillance programs for human immunodeficiency virus (HIV) to more accurately measure access to and retention in care across the HIV care continuum for persons living with HIV within their jurisdictions and to identify persons who may need public health services. However, traditional public health surveillance methods face substantial technological and privacy-related barriers to data sharing. Objective: This study developed a novel data-sharing approach to improve the timeliness and quality of HIV surveillance data in three jurisdictions where persons may often travel across the borders of the District of Columbia, Maryland, and Virginia. Methods: A deterministic algorithm of approximately 1000 lines was developed, including a person-matching system with Enhanced HIV/AIDS Reporting System (eHARS) variables. Person matching was defined in categories (from strongest to weakest): exact, very high, high, medium high, medium, medium low, low, and very low. The algorithm was verified using conventional component testing methods, manual code inspection, and comprehensive output file examination. Results were validated by jurisdictions using internal review processes. Results: Of 161,343 uploaded eHARS records from District of Columbia (N=49,326), Maryland (N=66,200), and Virginia (N=45,817), a total of 21,472 persons were matched across jurisdictions over various strengths in a matching process totaling 21 minutes and 58 seconds in the privacy device, leaving 139,871 uniquely identified with only one jurisdiction. No records matched as medium low or low. Over 80% of the matches were identified as either exact or very high matches. Three separate validation methods were conducted for this study, and they all found ≥90% accuracy between records matched by this novel method and traditional matching methods. Conclusions: This study illustrated a novel data-sharing approach that may facilitate timelier and better quality HIV surveillance data for public health action by reducing the effort needed for traditional person-matching reviews without compromising matching accuracy. Future analyses will examine the generalizability of these findings to other applications

Demographics and survival of AIDS cases with cancer, Washington, DC, 1996-2006

Background Washington, DC (DC) has one of the highest HIV/AIDS rates in the U.S and cancer is the second leading cause of death among DC residents. This study sought to examine the demographic characteristics and survival of persons with AIDS defining cancers (ADCs) compared to those with non-AIDS defining cancers (NADCs) between the early HAART era (1996-2001) and the late HAART era (2002-2006) in DC. Methods Cases reported from 1996-2006 to the DC Cancer Registry and the AIDS Surveillance Registry were linked using a probabilistic matching algorithm. Cases were included if the cancer occurred from 4 months to 60 months post-AIDS diagnosis and were stratified into ADCs and NADCs for analyses. Cancer diagnoses were stratified into the early and late HAART eras to compare the availability of HAART on the distribution of cancer type. Kaplan-Meier survival analysis and adjusted Cox proportional hazards regression were used to assess survival time and risk of death by cancer type. Results From 1996-2006, among 8,800 AIDS cases, 300 (3.4%) cases had a cancer diagnosis. NADCs accounted for 51% of cancers and were significantly more likely to be diagnosed with AIDS (p\u3c0.0001) and cancer (p\u3c0.0001) at 40 years or older and had a significantly longer median time from AIDS to cancer diagnosis (2.46 vs. 1.75 years, p=0.01) compared to ADCs. The most common ADCs were Kaposi sarcoma (40%) and non-Hodgkin lymphoma (NHL) (44%); the most common NADC cases were lung (20%), Hodgkin lymphoma (8%) and anal (8%) cancer. ADCs accounted for 56% of cancer cases in the late-HAART as compared to the early-HAART period (45%). Mortality within the first year of cancer diagnosis was similar (ADC 41% vs. NADC 37%) and no statistical difference in survival time was observed. In the adjusted model, NHL and lung cases were significantly more likely to die as compared to other cancers (NHL HR=3.06; Lung HR=3.44). Conclusions In DC, despite high HIV/AIDS and cancer prevalence, only a small proportion of AIDS cases also develop cancer with ADCs and NADCs being equally common. HAART availability does not seem to have altered survival among ADCs and NADCs. Survival among NHL cases was relatively low reflecting the need for increased access to care among HIV+ persons. NADC cases are most likely developing cancers related to advancing age with higher proportions of lung cancers being observed. Public health efforts should focus on lung cancer prevention and continued monitoring of HIV-infected persons for cancers

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort

Background Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. Methods We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. Results Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5–4.1); age 18–34 years, 10.8 (95% CI, 9.7–12.0); transgender women, 9.9 (95% CI, 6.9–14.0); Hispanics, 9.2 (95% CI, 7.2–11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1–8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. Conclusions STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation

Use of National Standards to Monitor HIV Care and Treatment in a High Prevalence City-Washington, DC.

We sought to benchmark the quality of HIV care being received by persons living with HIV in care in Washington, DC and identify individual-level and structural-level differences. Data from the DC Cohort, an observational HIV cohort of persons receiving outpatient care in DC, were used to estimate the Institute of Medicine (IOM) and Department of Health and Human Services (HHS) quality of care measures. Differences in care by demographics and clinic type were assessed using χ2 tests and multivariable regression models. Among 8,047 participants, by HHS standards, 69% of participants were retained in care (RIC), 95% were prescribed antiretroviral therapy (ART), and 84% were virally suppressed (VS). By IOM standards, 84% were in continuous care; and 78% and 80% underwent regular CD4 and VL monitoring, respectively. Screening for syphilis, chlamydia, and gonorrhea was 51%, 31%, and 26%, respectively. Older participants were 1.5 times more likely to be RIC compared to younger participants (OR: 1.5; 95% CI: 1.3, 1.8). Participants enrolled in community-based clinics were more likely to be RIC (OR: 1.7; 95% CI: 1.4, 2.0) versus those enrolled at hospital-based clinics. Older participants were more likely to achieve VS than younger participants (OR: 1.8; 95% CI: 1.5, 2.2) while Black participants were less likely compared to white participants (OR: 0.4; 95% CI: 0.3, 0.5). Despite high measures of quality of care, disparities remain. Continued monitoring of the quality of HIV care and treatment can inform the development of public health programs and interventions to optimize care delivery