Transmission of HIV and HCV within Former Soviet Union Countries.

Background: Following the collapse of the Union of Soviet Socialist Republic (USSR) in 1991, trans-border mobility increased within the former Soviet Union (FSU) countries. In addition, drug-trafficking and injection drug use began to rise, leading to the propagation and transmission of blood-borne infections within and across the FSU countries. To examine the transmission of blood-borne infections within this region, we analyzed the phylogenetic relationship of publically available sequences of two blood-borne viruses, hepatitis C virus (HCV) and human immunodeficiency virus (HIV), from FSU countries. Methods: We analysed 614 and 295 NS5B sequences from HCV genotypes 1b and 3a, respectively, from 9 FSU countries. From 13 FSU countries, we analysed 347 HIV gag and 1282 HIV env sequences. To examine transmission networks and the origins of infection, respectively, phylogenetic and Bayesian analyses were performed. Results: Our analysis shows intermixing of HCV and HIV sequences, suggesting transmission of these viruses both within and across FSU countries. We show involvement of three major populations in transmission: injection drug user, heterosexual, and trans-border migrants. Conclusion: This study highlights the need to focus harm reduction efforts toward controlling transmission of blood-borne infections among the abovementioned high-risk populations in the FSU countries.

Generational differences in current sexual behavior among Georgian reproductive-aged women.

Background: Following the collapse of the Soviet Union, there was a pronounced change in the availability of modern contraceptive methods and an accompanying shift in the knowledge and attitudes of Georgian women related to sexual behaviors. This study describes differences in sexual behaviors, condom use and family planning practices among several generations of reproductive-aged Georgian women. Methods: Study participants were recruited from three large cities in Georgia. Women >25 years were recruited from the Cervical Cancer Screening National Program by consecutive sampling; those <25 years were recruited from universities using random sampling. Data collection included self-administered, anonymous surveys. Bivariate analyses were conducted and adjusted prevalence ratios (PR) with 95% confidence intervals were computed. Results: Among the 350 participants, independent predictors of age at first sexual intercourse were age (aPR 0.27; 95% CI 0.12-0.57), level of education (aPR 0.23; 95% CI: 0.11-0.44), marital status (aPR 2.8;95% CI:1.3-6.0) and religion (aPR 4.01; 95% CI:1.17-13.68). Younger women were more likely to have a premarital sexual relationship compared to older women (RR=0.85; 95% CI: 0.80-0.89); older women were also significantly more likely to use family planning methods with a current partner (RR=2.15; 95% CI: 1.48-3.13). Similarly, advanced education was associated with family planning (RR=1.66; CI: 1.13-2.45). Conclusions: This study describes clear generational differences in current sexual behavior among Georgian women of reproductive age and these differences, especially in age at first sexual intercourse, premarital sexual relationship and use of contraceptive methods, are influenced by age, level of education, marital status and religion. This information is vital to designing contextually appropriate strategies to prevent sexually transmitted infections.

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation.

BACKGROUND: HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. METHODS AND RESULTS: Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti-Retroviral Therapy (SMART) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy (ART) treatment versus the untreated state (HIV replication) via 3 separate analyses: (1) a cross-sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short-term increases in some procoagulants (eg, 15% to 23% higher FVIII; P<0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [AT] and 6% to 10% lower protein C; P<0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P<0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. CONCLUSIONS: HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV-related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation.

Estonia at the threshold of the fourth decade of the AIDS era in Europe.

This article describes the trends of HIV/AIDS and related conditions in Estonia during the past decade (2000-2009), with special focus on the potential for epidemic transition. Key transmission determinants and major risk groups are examined and problems and barriers to fighting HIV/AIDS with possible applications in prevention and control are described. Estonian routine data sources and published literature were reviewed, supplemented with information from personal communication with physicians and public health specialists. For comparative European data, international HIV/AIDS and drug addiction surveillance documents, administrative data, and published literature were reviewed. In Eastern Europe (including Estonia) the predominant HIV transmission mode is injection drug use (IDU), closely followed by heterosexual transmission, an increasing risk factor for new cases. Although the contribution of cases acquired by sexual contact with high-risk partners such as IDUs is not known, characteristics of the sexual networks of IDUs may be important in determining the evolution of the HIV/AIDS epidemics in the region. In Estonia, despite major gaps in available data, the HIV/AIDS epidemic is still presumably confined to IDUs (and probably, to their sexual partners). In Eastern Europe, young women in IDU-non-IDU partnerships engaging in unprotected sex potentially serve as a bridge to the general population, yet knowledge of and research into the population characteristics and potential magnitude of bridging are limited. In Estonia, as in other Eastern European countries, HIV prevention and harm reduction initiatives should be tailored not only to the predominantly male HIV-positive IDU population, but also to their noninfected non-IDU female sexual partners.

The association of HIV infection with left ventricular mass/hypertrophy.

Left ventricular hypertrophy (LVH) is an independent predictor of major cardiovascular events. Cardiovascular risk is increased among human immunodeficiency virus (HIV)-infected patients. To assess LV mass/hypertrophy in HIV infection, 654 women enrolled in the Women's Interagency HIV Study underwent transthoracic echocardiography. There were 454 HIV-infected and 200 uninfected women, mean age 40.8 +/- 9.3 years. LV mass/height(2.7) was similar between the HIV-infected and the HIV-uninfected groups (41.4 +/- 11.1 vs. 39.9 +/- 10.3 g/h(2.7); p = 0.37). The prevalence of LVH was similar between the two groups (LVH by LV mass/height(2.7) criteria 15.0% vs. 13.0%, p = 0.29). Relative wall thickness (RWT), defined as the ratio of LV wall thickness to cavity diameter, was also similar between the HIV-infected and HIV-uninfected groups (0.36 +/- 0.05 vs. 0.37 +/- 0.06, p = 0.16). On multiple linear regression analysis adjusting for age, W/H ratio, triceps skinfold thickness, systolic/diastolic BP, diabetes, hypertension and dyslipidemia; HIV status (b = 2.08, p = 0.02, CI 0.27-3.88); weight (b per kg = 0.15, p < 0.01, CI 0.08-0.22); and smoking duration (b per one-year increase = 0.08, p = 0.03, CI 0.01-0.16) were independent correlates of LV mass/height(2.7) (Model R(2) = 0.20, p < 0.001). Weight (aOR = 1.04, CI 1.01-1.06) and smoking duration (aOR = 1.03, CI 1.01-1.06) were independent correlates of LVH. Being HIV negative, increased age, increased triceps skinfold thickness, and higher W/H ratio were independent correlates of higher RWT. Among HIV-infected women, higher LV mass was not associated with a history of AIDS-defining illness, nadir CD4(+) count <200 cells/microl, or with the duration of highly active antiretroviral therapy (HAART). Women taking NRTIs had higher LV mass. Higher RWT was associated with current CD4(+) count. In conclusion, HIV infection is associated with greater LV mass but not with a higher prevalence of LVH. Among HIV-infected women, RWT, but not LV mass, is associated with the degree of immunosuppression.

Interarm blood pressure differences in the women's interagency HIV study.

Hypertension has been reported in 8-32% of HIV-infected individuals. Large interarm blood pressure differences (IABPD) may cause misclassification of blood pressure (BP) status. The objectives of this study were to determine the magnitude and factors associated with IABPD in HIV-infected women and uninfected controls. Using automated devices, two BP recordings were measured and averaged from each arm in Brooklyn enrollees of the Women's Interagency HIV Study. Absolute IABPD was calculated for each patient. Among 335 subjects, 238 were HIV infected and 97 were uninfected. Mean systolic and diastolic IABPD were 6 +/- 5 mm Hg and 4 +/- 3 mm Hg, respectively. Twenty-six percent of subjects had systolic IABPD >10 mm Hg and 6% had systolic IABPD >20 mm Hg. Fifteen percent of subjects had diastolic IABPD >10 mm Hg. Interarm BP differences were not associated with HIV serostatus, CD4(+) cell count, and use of highly active antiretroviral therapy. Systolic IABPD >20 mm Hg was associated with obesity (ORadj 5.37, 95% CI 1.47, 19.65), and LDL cholesterol above 160 (ORadj 9.12, 95% CI 2.53, 32.88). Right arm BP measurement resulted in 10% of subjects with high/uncontrolled BP. Bilateral arm BP measurement increased the yield to 15% (p < 0.001). In conclusion, systolic and diastolic IABPD are common and appear to be of clinically important magnitude. Systolic IABPD are related to cardiovascular risk factors but not to HIV-related factors. Bilateral BP determination is important to detect and manage hypertension as well as for accurate cardiovascular risk assessment.

High prevalence of blood-borne virus infections and high-risk behaviour among injecting drug users in Tallinn, Estonia.

The HIV epidemic in Estonia is rapidly expanding, and injection drug users (IDUs) are the major risk group contributing to the expansion. A convenience sample of 159 IDUs visiting syringe-exchange programmes (SEPs) was selected to quantify the association of HIV-risk behaviours and blood-borne infections. A high prevalence of HIV, hepatitis B core antibody (HBVcore), hepatitis B surface antigen (HbsAg) and hepatitis C virus antibodies (56, 85.1, 21.3, and 96.2%, respectively) was associated with high-risk injections, unsafe sexual behaviour and alcohol abuse. These findings emphasize the importance of evidence-based secondary prevention among the HIV-infected, especially given the uncertain sustainability of antiretroviral and substance abuse treatments.

Relationship between health insurance and medical care for patients hospitalized with human immunodeficiency virus-related Pneumocystis carinii pneumonia, 1995-1997: Medicaid, bronchoscopy, and survival.

In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients.