HIV AND STI RISK FACTORS AMONG GEORGIAN YOUTH.

Designing effective interventions for youth to address STI/HIV risk factors requires local context knowledge. This study gathers information about STI/HIV knowledge among Georgian youth, identifies STI/HIV risk behaviors and quantifies associations between socio-demographic factors and risk practices with HIV/STIs knowledge. Cross-sectional survey was conducted among 411 students using self-administered questionnaire. Bivariate analysis was conducted and prevalence ratios with 95% confidence intervals were computed. Study participants were more knowledgeable about HIV/AIDS than other STIs, though still lacked information about HIV/AIDS transmission routes. Only 10.1% had ever received HIV testing. Men were less likely to have current permanent sex partner (44.5% vs 79.2%; PR=0.2; 95% CI:0.1-0.5) and more likely to have occasional sex partner past 12 months than women (51% vs 19%; PR=4.3; 95% CI:1.8-10.2). Study describes relatively low awareness of STIs in Georgian youth and revealed possibilities to influence STI transmission through designing gender-tailored public health interventions.

Evaluating the association of single-nucleotide polymorphisms with tenofovir exposure in a diverse prospective cohort of women living with HIV.

Higher exposure to tenofovir (TFV) increases the risk for kidney function decline, but the impact of genetic factors on TFV exposure is largely unknown. We investigated whether single-nucleotide polymorphisms (SNPs, n=211) in 12 genes are potentially involved in TFV exposure. Participants (n=91) from the Women's Interagency HIV Study, underwent a 24 h intensive pharmacokinetic sampling of TFV after witnessed dose and TFV area under the time-concentration curves (AUCs) were calculated for each participant. SNPs were assayed using a combination of array genotyping and Sanger sequencing. Linear regression models were applied to logarithmically transformed AUC. Those SNPs that met an a priori threshold of P<0.001 were considered statistically associated with TFV AUC. ABCG2 SNP rs2231142 was associated with TFV AUC with rare allele carriers displaying 1.51-fold increase in TFV AUC (95% confidence interval: 1.26, 1.81; P=1.7 × 10-5). We present evidence of a moderately strong effect of the rs2231142 SNP in ABCG2 on a 24 h TFV AUC.

Trends in Injection Risk Behaviors among People Who Inject Drugs and the Impact of Harm Reduction Programs in Ukraine, 2007-2013.

The study examined trends in injection risk behaviors among people who inject drugs (PWIDs) and assessed the impact of harm reduction programs in Ukraine during 2007-2013. We performed a secondary analysis of the data collected in serial cross-sectional bio-behavioral surveillance surveys administered with PWIDs in Ukraine in 2007, 2008, 2011, and 2013. Using data from 14 Ukrainian cities, we assessed short-term trends in injection risk behaviors with the Cochran-Armitage test for trend and multivariable logistic regression models, adjusted for age, sex, region, marital status, education level, occupation, age at injection drug use initiation, experience of overdose, and self-reported HIV status. The overall test for trend indicated a statistically significant decrease over time for sharing needle/syringe during the last injection (p < 0.0001), sharing needle/syringe at least once in the last 30 days (p < 0.0001), and using a common container for drug preparation (p < 0.0001). The prevalence of injecting drugs from pre-loaded syringes was high (61.0%) and did not change over the study period. After adjusting for all significant confounders and comparing to 2007, the prevalence of sharing needle/syringe during the last injection was unchanged in 2008 (OR = 1.06, 95% CI = 0.92, 1.21), and declined in 2011 (OR = 0.18, 95% CI = 0.15, 0.22) and 2013 (OR = 0.17, 95% CI = 0.14, 0.21). Sharing needles/syringes in the last 30 days significantly decreased when compared to that in 2007 (2008: OR = 0.81, 95% CI = 0.74, 0.89; 2011: OR = 0.43, 95% CI = 0.38, 0.47; and 2013: OR = 0.31, 95% CI = 0.27, 0.35). The prevalence of using common instruments for drug preparation also decreased compared to that in 2007 (2008: OR = 0.88, 95% CI = 0.85, 0.91; 2011: OR = 0.85, 95% CI = 0.85, 0.90; and 2013: OR = 0.74, 95% CI = 0.71, 0.76). The observed reduction in the prevalence of injection risk behavior over time is encouraging. Our findings suggest that prevention programs in Ukraine have positive impact and provide support for governmental expansion of these programs.

Pharmacogenetic Associations with ADME Variants and Virologic Response to an Initial HAART Regimen in HIV-Infected Women.

BACKGROUND: Clinical response to highly active antiretroviral therapy (HAART) varies among different populations. A portion of this variability may be due to variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of HAART. DESIGN: To identify genetic factors involved in virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort of HIV-infected women on HAART. A total of 569 HIV-positive participants from the Women's Interagency HIV Study who initiated HAART from 1994-2012 and had genotype data were included in these analyses. METHODS: Admixture maximum likelihood burden testing was used to evaluate gene-level associations between common genetic variation and virologic response (achieving <80 viral copies/mL) to HAART overall and with specific drug classes. Results: Six statistically significant (P<0.05) gene-level burden tests were observed with response to specific regimen types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were significantly associated with response to triple nucleoside reverse transcriptase inhibitor (NRTI) treatment. CONCLUSIONS: Although no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance (two and a half expected, six observed). It is likely that variation in one of the significant genes is associated with virologic response to certain HAART regimens. Further characterization of the genes associated with response to PI-based treatment is warranted.

The cascade of care in the Eastern European country of Georgia.

OBJECTIVES: Individual and public health benefits of antiretroviral therapy (ART) rely on successful engagement of HIV-infected patients in care. We aimed to evaluate the HIV care continuum in the Eastern European country of Georgia. METHODS: The analysis included all adult (age ≥ 18 years) HIV-infected patients diagnosed in Georgia from January 1989 until June 2012. Data were extracted from the national HIV/AIDS database as of 1 October 2012. The following stages of the HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care, retained in care, eligible for ART and virologically suppressed. RESULTS: Of 3295 cumulative cases of adult HIV infection reported in Georgia, 2545 HIV-infected patients were known to be alive as of 1 October 2012, which is 52% of the estimated 4900 persons living with HIV in the country. Of the 2545 persons diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had a viral load <400 HIV-1 RNA copies/mL. Overall, 39% of those diagnosed and 20% of those infected had a suppressed viral load. CONCLUSIONS: The findings of our analysis demonstrate that the majority of patients diagnosed with HIV infection are retained in care. Loss of patients occurs at each step of the HIV care continuum, but the major gap is at the stage of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.

Mean platelet volume is decreased in HIV-infected women.

OBJECTIVES: HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. METHODS: A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. RESULTS: The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/µL (95% confidence interval (CI) 238, 259 cells/µL) vs. 276 cells/µL (95% CI 265, 287 cells/µL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. CONCLUSIONS: HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.

Occupational exposure to body fluids among health care workers in Georgia.

BACKGROUND: Health care workers (HCWs) are at increased risk of being infected with blood-borne pathogens. AIMS: To evaluate risk of occupational exposure to blood-borne viruses and determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among HCWs in Georgia. METHODS: The sample included HCWs from seven medical institutions in five cities in Georgia. A self-administered questionnaire was used to collect information on demographic, occupational and personal risk factors for blood-borne viruses. After obtaining informed consent, blood was drawn from the study participants for a seroprevalence study of HBV, HCV and HIV infections. RESULTS: There were 1386 participating HCWs from a number of departments, including surgery (29%), internal medicine (19%) and intensive care (19%). Nosocomial risk events were reported by the majority of HCWs, including accidental needlestick injury (45%), cuts with contaminated instruments (38%) and blood splashes (46%). The most frequent risk for receiving a cut was related to a false move during a procedure, reassembling devices and handing devices to a colleague. The highest proportion of needlestick injuries among physicians (22%) and nurses (39%) was related to recapping of used needles. No HIV-infected HCW was identified. Prevalence of HCV infection was 5%, anti-HBc was present among 29% with 2% being HBsAg carriers. CONCLUSIONS: Data from this study can be utilized in educational programs and implementation of universal safety precautions for HCWs in Georgia to help achieve similar reductions in blood-borne infection transmission to those achieved in developed countries.

Population-based type-specific prevalence of high-risk human papillomavirus infection in Estonia.

BACKGROUND: Effective prophylactic vaccines are available against human papillomavirus (HPV) types 6, 11, 16, and 18 which are licensed for routine use among young women. Monitoring is needed to demonstrate protection against cervical cancer, to verify duration of protection, and assess replacement frequency of non-vaccine types among vaccinated cohorts. METHODS: Data from a population-based study were used to assess the type-specific prevalence of HPV in a non-vaccinated population in Estonia: 845 self-administered surveys and self-collected vaginal swabs were distributed, 346 were collected by mail and tested for HPV DNA from female participants 18-35 years of age. RESULTS: The overall HPV prevalence (weighted estimate to account for the sampling method) in the study population (unvaccinated women aged 18-35) was calculated to be 38% (95% CI 31-45%), with estimated prevalences of high- and low-risk HPV types 21% (95% CI 16-26%), and 10% (95% CI 7-14%), respectively. Of the high-risk HPV types, HPV 16 was detected most frequently (6.4%; 95% CI 4.0-9.8%) followed by HPV 53 (4.3%; 95% CI 2.3-7.2%) and HPV 66 (2.8%; 95% CI 1.3-5.2%). CONCLUSIONS: We observed a high prevalence of total and high-risk type HPV in an Eastern European country. The most common high-risk HPV types detected were HPV 16, 53, and 66.

Trends in the epidemiology of bacterial sexually transmitted infections in eastern Europe, 1995-2005.

BACKGROUND: Sexually transmitted infections (STI) are a significant public health problem both worldwide and in Europe. This article reviews trends in the epidemiology of the major bacterial STI in eastern European countries, their key determinants, as well as challenges and opportunities for enhancing STI control in the region. SEARCH STRATEGY: Publications were sought through computerised searches in PubMed from 1995 to 2008 using using free text and relevant medical subject headings with no language restrictions. Conference abstracts and other unpublished manuscripts were excluded. RESULTS: The reported rates of STI in many eastern European countries have either decreased (syphilis and gonorrhoea in the eastern/Russian regions, gonorrhoea throughout eastern Europe) or been relatively stable (syphilis in the southeastern region, chlamydia throughout eastern Europe), in the past decade, but are still significantly higher than in western Europe. There is a significant east-west geopolitical gradient in reported STI rates throughout eastern Europe (STI rates: Russia/eastern region>>southeastern region>central region). Challenges for STI control include: the need to strengthen public health components of control; improvements in surveillance and improvement, as well as quality assurance, in diagnostic strategies. Gains in STI control may be achieved through greater collaboration and harmonisation of practicss at the European level.

The prevalence of chlamydial infection in Estonia: a population-based survey.

The aim of this study was to estimate the prevalence of Chlamydia trachomatis infection among Estonian men and women by a cross-sectional study based on the screening of a probability sample of the residents of Tartu using participant-collected, mail-delivered testing for C. trachomatis complemented with the self-administered questionnaire. Full participation as defined by returning both the questionnaire and specimen was 34% (n = 479; 95% confidence interval [CI] 32-37%). Study participation was 40% (n = 560; 95% CI 37-43%) for subjects returning either or both the study questionnaire and specimen. After weighing the population distribution, the prevalence estimate for the age group of 18-35 years was 5.4% (95% CI 3.0-7.5%), 6.9% (95% CI 3.6-10.3%) among women and 2.7% (95% CI 0.3-5.0%) among men. The number of sexual partners in the past 12 months was the strongest predictor of infection.

Peripheral arterial disease in HIV-infected and uninfected women.

OBJECTIVE: Although HIV infection has been associated with increased risk of subclinical atherosclerosis and cardiovascular events, peripheral arterial disease (PAD) has not been assessed in HIV-infected patients. The objective of this study was to determine the prevalence of, and risk factors for, PAD using ankle-brachial index (ABI) measurement in HIV-infected and uninfected women. METHODS: ABI was determined for 335 participants in the Women's Interagency HIV Study (WIHS). A cross-sectional analysis was conducted to determine factors associated with high (>or=1.40) ABI. RESULTS: The prevalence of low ABI (or=1.40) was 6.9% (n=23). The prevalence of low ABI was too low to allow risk factor analysis. On multivariate analysis, factors associated with high ABI were current cigarette smoking [adjusted odds ratio (OR(adj)) 2.53, 95% confidence interval (CI) 0.99-6.43], being underweight (OR(adj) 11.0, 95% CI 1.61-75.63) and being overweight (OR(adj) 5.40, 95% CI 1.13-25.89). CONCLUSIONS: Although the prevalence of ABI or=1.40 was unexpectedly high. Further studies are indicated to determine the clinical significance of high ABI and its relation to the risk of cardiovascular events in HIV-infected women.

Epidemiology and natural history of ligase chain reaction detected chlamydial and gonococcal infections.

OBJECTIVES: Ligase chain reaction (LCR) technology has dramatically increased the sensitivity of tests for sexually transmitted infections (STIs). It is unknown whether low copy infections (LCR positive, culture negative) have any clinical consequences. We assessed the clinical significance of untreated low copy Chlamydia trachomatis and Neisseria gonorrhoeae infections in a cohort of sexually active women. METHODS: We studied a cohort of sexually active women followed at 6 month intervals for up to 3 years. Frozen urine specimens from 181 women with negative cultures for C. trachomatis and N. gonorrhoeae who were 'high risk' (defined as being less than 40 years old at baseline, and having either Trichomonas vaginalis at baseline or a history of more than one sexual partner during the 12 months before baseline) were tested for C. trachomatis and N. gonorrhoeae by LCR (Abbott Laboratories, Abbott Park, IL, USA). The specimens from all visits for each person were pooled and LCR was performed on the pool. Laboratory results were linked to clinical information. We also tested all urine samples obtained from patients with a positive culture. RESULTS: 10 additional infections (nine C. trachomatis and one N. gonorrhoeae) were detected with LCR technique. None of the women with low copy infection had evidence of subsequent pelvic inflammatory disease or ectopic pregnancy. Pooling of urine samples resulted in a 47% decline in the number of tests performed. CONCLUSIONS: Additional STIs can be identified when using LCR. Pooling of urine specimens is a cost saving technique for C. trachomatis and N. gonorrhoeae testing.

Sexual activity and condom use among Eastern European adolescents--the Study of Hungarian Adolescent Risk Behaviours.

While rates of HIV and STD infection in Eastern Europe are increasing rapidly, little is known about sexual behaviour, including condom use, among Eastern European youths. The Study of Hungarian Adolescent Risk Behaviours was designed to assess the knowledge, attitudes, and behaviours of adolescents studying in secondary schools in Budapest, Hungary. Students (n =3486) in a random sample of public secondary schools completed a self-administered questionnaire, including measures of sexual activity and condom use. Thirty-eight percent of students reported ever having had vaginal intercourse. Condom use by those reporting having had sex in the past five weeks was classified as consistent/every time (40%); irregular (25.6%); and none (34.3%). Multivariate analysis revealed positive opinions about condoms, fear of AIDS, and initiation of condom use by both partners to predict more frequent condom use. Implications for targeted AIDS/STD education and prevention among adolescents are discussed.

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

HIV-related Pneumocystis carinii pneumonia in older patients hospitalized in the early HAART era.

OBJECTIVE: To determine whether older age continues to influence patterns of care and in-hospital mortality for hospitalized persons with HIV-related Pneumocystis carinii pneumonia (PCP), as determined in our prior study from the 1980s. DESIGN: Retrospective chart review. PATIENTS/SETTING: Patients (1,861) with HIV-related PCP at 78 hospitals in 8 cities from 1995 to 1997. MEASUREMENTS: Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; in-hospital mortality. MAIN RESULTS: Compared to younger patients, patients > or =50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P <.001), have mild or moderately severe PCP cases at admission (89% vs 96%, P <.002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P <.003). However, age was not a significant predictor of mortality after adjustment for severity of PCP and timeliness of therapy. CONCLUSIONS: While inpatient PCP mortality has improved by 50% in the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, increased severity of illness at admission, and delays in initiation of PCP-specific treatments among older individuals--factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons > or =50 years of age who present with new pulmonary symptoms should be encouraged.

Human herpesvirus 8 infection and Kaposi's sarcoma among human immunodeficiency virus-infected and -uninfected women.

Little is known about the epidemiology of human herpesvirus 8 (HHV-8) infections among women. A cross-sectional study was conducted of HHV-8 infection among human immunodeficiency virus (HIV)-infected and high-risk HIV-uninfected women. Serological tests with noninduced (latent) and induced (lytic) HHV-8 antigens were used to detect infection among 2483 participants of a multisite cohort. Reactivity to latent antigen was present in 4.1% and to induced antigens in 12.0% of women. Seven of 8 women who reported Kaposi's sarcoma had HHV-8 antibodies. Among HIV-positive women, HHV-8 infection was associated with use of crack, cocaine, or heroin (76% vs. 65%; P<.001), past syphilis (29% vs. 20%; P<.001), an injection drug-using male sex partner (61% vs. 53%; P=.014), black race (P=.010), and enrollment site (P=.015). In multivariate analysis, HIV infection, older age, past syphilis, black race, and enrollment site were independently associated with HHV-8 infection. In this cohort of North American women, HHV-8 infection was associated with HIV infection, drug use, and risky sexual behavior.

New mothers' knowledge and attitudes about perinatal human immunodeficiency virus infection.

OBJECTIVES: To assess new mothers' attitudes toward perinatal human immunodeficiency virus (HIV) testing, their knowledge about perinatal HIV, and their trust of government and scientists. METHODS: In a cross-sectional survey of 1362 postpartum women at four United States locations in 1997, a standardized interview was administered to new mothers 24-48 hours postpartum to determine their HIV test acceptance, attitudes, and knowledge. RESULTS: Seventy-five percent of women who were offered HIV tests reported being tested. Although 95% of women were aware of perinatal HIV transmission, only 60% knew that HIV can be transmitted through breast-feeding, and only 51% knew of medication to prevent perinatal transmission. Eighty-four percent of women thought that all pregnant women should be tested for HIV, and 60% thought that prenatal HIV testing should be legally mandated. Twenty percent of women indicated mistrust of government and scientists regarding origins of HIV and potential cures for AIDS. Knowledge about perinatal transmission was unrelated to receipt of prenatal HIV tests. When other factors were controlled for, mistrust was not significantly associated with getting tested. CONCLUSION: Incomplete knowledge of prevention of perinatal HIV transmission and mistrust were prevalent among new mothers. Knowledge deficits or mistrust did not appear to reduce reported prenatal test rates, but our data suggest that future public health efforts need to educate women about methods of preventing perinatal HIV transmission and at enhancing their trust in the public health system.

High prevalence of HIV risk-behavior and the identification of predictors for sharing injecting materials among young drug users in Prague, Czech Republic.

This study is one of the first studies in the Czech Republic evaluating the extent of the HIV epidemic among drug users. Interview data on demographics, drug use, sexual practices, and HIV knowledge and risk perception were obtained from study participants and a saliva sample was obtained for an HIV antibody test. Although the HIV infection rate is low (0.2%), the prevalence of high risk behaviors, such as sharing injecting equipment and unsafe sexual practices, indicate a potential for rapid HIV spread in this high risk population. Preventive measures need to be targeted toward drug users, especially those of younger age and women.

The relationship between virus load response to highly active antiretroviral therapy and change in CD4 cell counts: A report from the Women's interagency HIV study.

The relationship between the pattern of virus load response to highly active antiretroviral therapy (HAART) and CD4 lymphocyte response was assessed in a cohort of 249 human immunodeficiency virus (HIV) type 1-infected women at 3 times: 1 before and 2 after initiation of therapy, with follow-up of 6-12 months. Patients with a durable response to HAART (i.e., >1 log decrease in HIV-1 RNA sustained for the study periods) had a continuous and significant increase in CD4 cell counts over time, whereas those with no response (<0.5 log decrease in HIV-1 RNA) had a slight decline. Patients with a mixed response (initial decrease >1 log, followed by a subsequent decrease <0.5 log) had an increase in CD4 cell count, followed by a plateau. The trend in CD4 cell count differed significantly by response to HAART, with those patients who experienced a durable response having significantly higher CD4 cell counts than others.