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Adipose expansion during obesity has remarkable similarities with the growth of solid tumors. These similarities are the following: the capability to unlimited expansion; reversible plasticity; induction of angiogenesis; chronic inflammation; remodeling and disfunction; systemic influence on the organism; hormone production; production of miRNAs that influence other tissues; immunosuppression; DNA damage and resistance to apoptosis; infiltration in other organs and tissues. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Transgenic inducible zebrafish tumor model was used to verify the above hypothesis. We described several genes, which originated in fish and were expressed in fish tumors. Their human orthologs LEP, SPRY1, PPARG, ID2, and CIDEA acquired functions connected with human adipose. They are also involved in tumor development in humans. If the hypothesis of the evolutionary origin of mammalian adipose from the ancestral benign hereditary tumors is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targeting LEP, SPRY1, PPARG, ID2, and CIDEA gene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors. Citation Format: Andrei P. Kozlov. Mammalian adipose has many tumor features, which suggests the possible way of its evolutionary origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6077.

According to the hypothesis of the evolutionary role of tumors, evolutionarily new genes should be specifically expressed in tumors [A.P. Kozlov, 2014]. Indeed, TSEEN (tumor specific evolutionarily novel) genes were described by us [Kozlov, 2016]. 1015 genes were identified by the Protein Historian program as evolutionary novel for humans, that is, originated in humans, and 1392 as evolutionarily young, that is, originated in primates. As a result of analyzing the GTEx database data, we have shown that out of 1015 evolutionarily new human genes and 1392 evolutionarily young human genes, 309 genes and 592 genes are not expressed in any of 33 normal tissues, respectively. The expression level of 101 evolutionarily new human genes originated in humans and 233 evolutionarily young human genes originated in primates is significant in most tumors, according to transcriptome data from the TCGA database. Samples of 101 evolutionarily novel human genes and 233 evolutionarily young human genes were selected, which are present only in the genomes of humans and primates, not expressed in normal tissues, and expressed in one or more tumors in 10-100% of patients.For Theria and Eutheria, the similar distribution was as follows: among 365 and 896 genes novel for these taxons, 71 and 124 genes, respectively, are not expressed in normal human tissues, respectively, but at the same time have tumor-specific expression pattern (inclusion criteria of expression - fpkm >2 in 10-100% of patients).There are also 898 genes, originated in mammalia and not expressed in normal human tissues. 119 of them are expressed in at least 1 or more tumors in 10-100% of patients.The TSEEN genes database allows [us] to select genes according to their evolutionary age and expression pattern in normal and tumor tissues. We can retrieve gene(s), which are expressed tumor-specifically and are evolutionarily young or novel.As far as TSEEN genes have many immunogenic epitopes they could be promising targets for development of universal prophylactic and therapeutic antitumor vaccines, as well as universal markers for cancer laboratory diagnostics.Created TSEEN genes database is available at: https://tseendb.org/#/ Citation Format: Ekaterina Matyunina, Andrei Makashov, Andrei P. Kozlov. TSEEN genes database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3350.

To detect acute HIV infections (AHIs) in real time among people who inject drugs (PWID) in St. Petersburg, Russia and to test the feasibility of this approach. Prospective cohort study. One hundred seronegative or acutely HIV-infected at screening PWID were enrolled and followed until the end of the 12-month pilot period. Each participant was evaluated, tested, and counseled for HIV monthly. Two HIV tests were used: HIV antibody and HIV RNA PCR. If diagnosed with AHI, participants were followed weekly for a month; then, monthly for 3 months; and then, quarterly for the duration of the follow-up period. HIV risk behavior was assessed at each study visit. Most enrolled PWID were 30-39 years old, male, completed high school or more, not employed full-time, heroin users, and frequently shared injection paraphernalia. AHI prevalence at screening was 1.8% [95% confidence interval (CI): 0.4, 5.5]. Three participants with AHI at enrollment represented 3% (95% CI: 0.6, 8.5) of the 100 participants who consented to enroll. Among the HIV-uninfected participants (n = 97), the AHI incidence over time was 9.3 per 100 person-years. Persons with AHI were more likely to report alcohol intoxication within the prior 30 days. This was the first study to detect AHI using a cohort approach. The approach proved to be feasible: recruitment, retention, AHI detection, and virological endpoints were successfully reached. A cost analysis in a real-world setting would be required to determine if this strategy could be brought to scale. The study revealed continued high HIV incidence rate among PWID in St. Petersburg, Russia and the importance of prevention and treatment programs for this group.

Earlier we showed that human genome contains many evolutionarily young or novel genes with tumor-specific or tumor-predominant expression. We suggest calling such genes Tumor Specifically Expressed, Evolutionarily New (TSEEN) genes. In this paper we performed a study of the evolutionary ages of different classes of human genes, using homology searches in genomes of different taxa in human lineage. We discovered that different classes of human genes have different evolutionary ages and confirmed the existence of TSEEN gene classes. On the other hand, we found that oncogenes, tumor-suppressor genes and differentiation genes are among the oldest gene classes in humans and their evolution occurs concurrently. These findings confirm non-trivial predictions made by our hypothesis of the possible evolutionary role of hereditary tumors. The results may be important for better understanding of tumor biology. TSEEN genes may become the best tumor markers.

Orthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs.We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon of OTP gene. The second exon was 2345bp long and located in the second intron of OTP gene.The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequence OTP-AS1 (OTP- antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions.Author summaryPreviously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer.In our study we found a new cancer-testis long noncoding RNA (OTP-AS1), which is an antisense of protein-coding cancer-testis gene (OTP). Thus, OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression. OTP-AS1 may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy.Part of OTP-AS1 gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This links OTP-AS1 gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74-35.65) and 7.76 (95 % CI 3.51-17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15-1.08) without a statistically significant difference between the two groups (log rank test statistic X(2) = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.

Cultural adaptation is an important step in the process of implementing health promotion interventions that, having been proven to be effective in one culture, are being applied in another. This study describes the results of a formative investigation to culturally adapt a STI/HIV risk reduction intervention for use in St. Petersburg, Russia. Analyses of data from brief elicitation interviews, focus groups, community experts, and a pilot test of the adapted intervention identified environmental, cognitive-information processing, and affect-motivation factors that needed to be addressed during the adaptation process. The participant/counselor relationship was adapted to reflect a hierarchical (cf. collaborative) relationship in order to accommodate Russian expectations about patient interactions with healthcare experts. Key skills building activities (e.g., identification of personal risk behaviors, role-playing) were approached gradually or indirectly in order to maintain participants' engagement in the intervention, and close-ended questions were added to assist participants in understanding unfamiliar concepts such as "triggers" and self-efficacy. Information about the prevalence of HIV/STI infections and alcohol use included data specific to St. Petersburg to increase the personal relevance of these materials and messages. Intervention components were tailored to participants' risk reduction and informational needs. No gender differences that would have justified adaptation of the intervention approach or content were noted. Examples of specific adaptations and the key issues to attend to when adapting behavioral interventions for use in Russian clinical settings are discussed.

The study examined the efficacy of a brief theory-based counseling intervention to reduce sexual HIV risk behaviors among STI clinic patients in St. Petersburg, Russia. Men and women (n=307) were recruited to receive either: (1) a 60-minute motivational/skills-building counseling session dealing with sexual HIV risk reduction, or (2) written HIV prevention information material. Participants completed baseline and three- and six-month assessments in the period between July 2009 and May 2011. Compared to the control group, the face-to-face counseling intervention showed significant increases in the percentage of condom use and consistent condom use, and significant decreases in the number of unprotected sexual acts and frequency of drug use before sex at three-months follow-up. Intervention effects dissipated by six months. The brief counseling intervention may effectively reduce HIV sexual risk behaviors and enhance protective behaviors among STI clinic patients in Russia. Short-term positive effects were achieved with a single one hour counseling session.

We investigated whether inebriation was associated with having non-main partners and unprotected sex with non-main partners and whether drinking motivations were associated with sexual risk behaviors among patients attending an STD clinic in St Petersburg, Russia. A cross-sectional behavior survey was applied to 362 participants between 2008 and 2009. Multivariate logistic regression was used for analysis. At-risk drinking per Alcohol Use Disorders Identification Test (AUDIT-C) criteria (OR 2.5, 95% CI 1.4–4.4) was independently associated with having non-main sexual partners. Inebriation (OR 3.2, 95% CI 1.3–8.1) but not at-risk drinking or drinking prior to sex was associated with unprotected sex with non-main partners. Among drinkers, the consumption of alcohol to facilitate sexual encounters (OR 2.7, 95% CI 1.6–4.5) was associated with having non-main sexual partners. HIV prevention programs in Russia must address inebriation in addition to conventional patterns of problem drinking such as those measured by AUDIT-C and consider individuals’ motivations to drink that lead to sexual risk taking.

Sexually transmitted diseases (STDs) are a major public health problem in Russia.1 Although recent research demonstrates a decreasing incidence for syphilis and gonorrhea, and a stable incidence of genital chlamydial infection from mid-1990s to 2005 in Russia, these incidences are still higher than those of western European countries.1 The number of people living with HIV is also an important public health problem and has increased rapidly since mid-1990s.2,3 It is estimated that approximately 940,000 adults are currently living with HIV and the adult prevalence reaches 1.1%.4 In Russia, the HIV epidemic has been observed primarily among injection drug users.2 However, concerns have been raised that the epidemic is spreading to the general population through heterosexual transmission, which may exacerbate the HIV epidemic in Russia.2 The relatively higher incidence of STDs might have contributed, and continue contributing, to the prevalence of HIV in Russia because STDs facilitate HIV sexual transmission.5 Concurrent sexual partnerships play an important role in the spread of STDs and HIV.6–8 Results from mathematical models demonstrated that concurrent sexual partnerships may accelerate the spread of STDs and HIV by increasing the likelihood of exposure to infected persons and reducing the time between sexual contacts among infected and susceptible persons.9–11 Empirical studies have found that sexual concurrency is associated with a higher risk of STDs.12,13 For example, a study conducted among adolescents attending a municipal STD clinic in San Francisco showed that the odds of having STDs for adolescents with concurrent partnerships were 60% higher than those without concurrent partnerships after adjusting for the number of sexual partners.13 In addition, sexual concurrency has been hypothesized to contribute to the generalized epidemics of HIV in sub-Saharan Africa.14,15 Most concurrency studies focus on individual's practice of having concurrent partners (individual concurrency). There are relatively few studies that consider the effect of having partners who engage in concurrent sexual partnerships (partner concurrency) on an individual's risk for STDs. However, an individual's risk for STDs is associated with risk behaviors of both members of a sexual partnership which means that if an individual has a sexual partner who engages in concurrent sexual partnerships, this individual's risk of STDs may be high even if he/she only has 1 sexual partner for a long time. Because data on sexual concurrency (either an individual's or a person's sexual partner's concurrency) are very limited in Russia, we conducted a study in St. Petersburg, Russia, during 2006 to 2008 to investigate the following aims: (1) to examine the prevalence and correlates of both individual and partner concurrency among adults attending 2 STD clinics, and (2) to identify whether individual or partner concurrent sexual partnerships are associated with STDs.

We conducted a cross-sectional study to determine whether the time between two consecutive sexual partnerships (gap) is associated with sexually transmitted infections (STIs) in Russia. A self-administered questionnaire was administered to STI clinic patients in St. Petersburg and participant’s STI data at the time of enrollment in the study was collected from medical charts. The length of the gap between partnerships was divided into four categories: overlapping (0 or negative gap), short gaps (1–90 days), mid-length gaps (91–365 days), and long gaps (366 days or more). Among the 659 respondents, 22.6% had overlapping partnerships, and 13.7, 4.2, and 59.5% had short, mid-length and long gaps, respectively. Short gaps (OR 2.34; 95% CI 1.38–3.95), but not overlapping relationships, were independently associated with STIs when contrasted against long term gaps. HIV prevention programs for Russian STI clinic patients should therefore focus also on prolonging the gap between consecutive, monogamous sexual partnerships.

Background: Russia has one of the world’s fastest growing HIV epidemics and it has been largely concentrated among injection drug users (IDU). St Petersburg, Russia’s second largest city, is one of the country’s regions that has been most affected by the HIV epidemic. To monitor the current epidemic situation, we sought to estimate recent HIV incidence among IDU in St Petersburg. Methods : In a cross-sectional study of 691 IDU recruited during 2005–08, HIV incidence was estimated by two methods: a retrospective cohort analysis and BED capture enzyme immunoassay (EIA) results. Socio-demographic and behavioural correlates of incident infections and spatial patterns were examined. Results: In the retrospective cohort analysis, the incidence rate was estimated to be 14.1/100 person-years [95% confidence interval (CI) 10.7–17.6]. Using results of BED EIA and two correction formulas for known misclassification, incidence estimates were 23.9 (95% CI 17.8–30.1) and 25.5 (95% CI 18.9–32.0) per 100 person-years. Independent correlates of being recently infected included current unemployment ( P = 0.004) and not having injected drugs in the past 30 days ( P = 0.03). HIV incident cases were detected in all but one district in the city, with focal areas of transmission observed to be expanding. Conclusions: High HIV incidence among IDU in St Petersburg attests to continued growth of the epidemic. The need for expansion of HIV prevention interventions targeted to vulnerable populations throughout the city is urgent. These results also suggest that the BED EIA may over-estimate incidence even after correction for low specificity.

The Sexual Acquisition and Transmission of HIV Cooperative Agreement Program (SATHCAP) examined the role of drug use in the sexual transmission of the human immunodeficiency virus (HIV) from traditional high-risk groups, such as men who have sex with men (MSM) and drug users (DU), to lower risk groups in three US cities and in St. Petersburg, Russia. SATHCAP employed respondent-driven sampling (RDS) and a dual high-risk group sampling approach that relied on peer recruitment for a combined, overlapping sample of MSM and DU. The goal of the sampling approach was to recruit an RDS sample of MSM, DU, and individuals who were both MSM and DU (MSM/DU), as well as a sample of sex partners of MSM, DU, and MSM/DU and sex partners of sex partners. The approach efficiently yielded a sample of 8,355 participants, including sex partners, across all four sites. At the US sites—Los Angeles, Chicago, and Raleigh–Durham—the sample consisted of older (mean age = 41 years), primarily black MSM and DU (both injecting and non-injecting); in St. Petersburg, the sample consisted of primarily younger (mean age = 28 years) MSM and DU (injecting). The US sites recruited a large proportion of men who have sex with men and with women, an important group with high potential for establishing a generalized HIV epidemic involving women. The advantage of using the dual high-risk group approach and RDS was, for the most part, the large, efficiently recruited samples of MSM, DU, and MSM/DU. The disadvantages were a recruitment bias by race/ethnicity and income status (at the US sites) and under-enrollment of MSM samples because of short recruitment chains (at the Russian site).

In this study, we investigated how individual attributes, dyad characteristics and social network characteristics may influence engaging in receptive syringe sharing, distributive syringe sharing and sharing cookers in injecting partnerships of IDUs in St Petersburg, Russia. We found that all three levels were associated with injecting equipment sharing, and that dyad characteristics were modified by characteristics of the social network. Self-reported HIV discordance and male gender concordance played a role in the risk of equipment sharing. Dyad interventions may not be sufficient to reduce injecting risk in IDU partnerships, but a combination of dyad and network interventions that target both IDU partnerships and the entire IDU population may be more appropriate to address injecting risk among IDUs.

The purpose of this analysis was to estimate human immunodeficiency virus (HIV) prevalence and testing patterns among injection drug users (IDUs) in St. Petersburg, Russia. HIV prevalence among 387 IDUs in the sample was 50%. Correlates of HIV-positive serostatus included unemployment, recent unsafe injections, and history/current sexually transmitted infection. Seventy-six percent had been HIV tested, but only 22% of those who did not report HIV-positive serostatus had been tested in the past 12 months and received their test result. Correlates of this measure included recent doctor visit and having been in prison or jail among men. Among the 193 HIV-infected participants, 36% were aware of their HIV-positive serostatus. HIV prevalence is high and continuing to increase in this population. Adequate coverage of HIV testing has not been achieved, resulting in poor knowledge of positive serostatus. Efforts are needed to better understand motivating and deterring factors for HIV testing in this setting.

Aims: This study investigates whether sexual transmitted behaviors and infections (STIs) among injection drug users (IDUs) may promote the spread of HIV among and beyond IDUs in Russia. Methods: We conducted a cross-sectional survey of behavior and tested for STIs in a convenience sample of 159 IDUs in St. Petersburg, Russia. Results: The median age was 27 and 57% were male. Almost all were sexually active, half had casual partners and 40% reported ≧2 sex partners in the previous 3 months. Of those who answered, 81% reported sex without condoms, 44% reported having sex with at least one partner who was not an IDU. Of 139 (87%) subjects who were actively injecting, 29% reported receptive syringe sharing. Twenty percent of subjects were seropositive for HIV-1 and 42% of HIV-1-negative subjects tested positive for an STI. Conclusions: The sample exhibited high levels of sexual risk behaviors and STIs, and a large proportion had sexual partners who were not IDUs. This population requires comprehensive interventions that ensures access to condoms and sterile injection supplies and that encourage safer sexual behaviors in an attempt to keep sexual transmission of HIV low.

Human immunodeficiency virus (HIV)-1 subtype A strains circulating among the majority of HIVinfected individuals in the former Soviet Union (FSU) countries demonstrate low genetic diversity. The consensus sequence of the FSU region-specific isolate has been used for the candidate DNA vaccine development. We constructed recombinant plasmids with four viral genes: env (gp140), gag, pol (reverse transcriptase), and nef. We immunized BALB/c mice intramuscularly using equimolar mixture of four recombinant plasmids, and observed significant cytotoxic T lymphocyte response and specific CD8(+) cell production against cells presenting HIV-1 peptides. Overall, the Th1 pathway of immune response clearly dominated. Immunological properties of this candidate DNA vaccine against HIV-1 suggest the possibility of its further study in clinical trials.

To provide an overview of the National Institute of Mental Health (NIMH) Collaborative HIV/STD Prevention Trial taking place in five populations at risk of HIV and sexually transmitted diseases in China, India, Peru, Russia, and Zimbabwe, including the rationale, study management, methods, and proposed data analyses.The Trial will scientifically evaluate the effectiveness of the community popular opinion leader (C-POL) community-level HIV prevention intervention that was adapted for use in the various cultures within the resource limitations faced by service providers in world regions threatened by high rates of HIV infection.The study phases consist of an ethnographic study, pilot studies, an epidemiological study, and a community-randomized trial. The Trial uses the C-POL intervention, which researchers selected on the basis of research that shows the intervention's success in populations vulnerable to HIV risk behavior in the United States, and has the potential to be applied in a variety of international settings.Trial results will be tabulated by and across country by randomization assignment. Results will include a careful review of data to substantiate original assumptions used in the study design. Data collection will not conclude until August 2007.Although data collection is incomplete, researchers have learned lessons throughout the development of the study. These include the importance of preliminary epidemiological studies; the close monitoring of biological testing, follow-up rates and process measures at international sites; the tailoring of assessments and interventions to various cultures; regular communication; and a review of the timeline to accommodate Institutional Review Board clearances.

To determine the feasibility of using audio computer-assisted self-interviewing (ACASI) for data collection in developing countries, and to compare responses to questions eliciting sensitive information about sexual behavior using ACASI versus computer-assisted personal interviewing (CAPI) in five developing countries.A feasibility study determined whether ACASI could be used in populations in developing countries. A follow-up, randomized crossover study compared responses to questions eliciting sensitive information about sexual behavior using ACASI versus CAPI.The NIMH Collaborative HIV/STD Prevention Trial conducted a feasibility study of ACASI in convenience samples in China, India, Peru, and Russia, then a randomized crossover ACASI versus CAPI study among volunteers in these countries plus Zimbabwe.Approximately equal numbers of men and women completed the feasibility study; the results suggested a high comfort level among participants. Married respondents in China and India appeared to give unreliable responses on sexual activity. In the crossover study, the pattern of responses to sensitive questions showed few differences. In China, higher rates of sexual risk were reported on CAPI. In Peru and Russia, differences by mode were found in the number of partners in the past year.Despite variable computer experience and literacy, feasibility study participants reported ease in completing ACASI, and preferred a computer to an interviewer for answering sensitive questions, or had no preference. In the crossover study, most participants gave similar responses on both modes of survey administration. ACASI appears to be feasible in these settings, although low literacy may pose problems if participants cannot clarify questions.

The HIV epidemic in Russia, one of the world's fastest growing, has been concentrated mostly among people who inject drugs (PWID). We sought to explore the epidemiology of the epidemic in St. Petersburg by sampling from the highest risk groups of PWID and men who have sex with men (MSM) and use viral sequencing data to better understand the nature of the city's epidemic. Serological testing confirmed an HIV prevalence among PWID in excess of 40%. All but 1 of 110 PWID whose blood samples were tested for genetic diversity were infected by subtype A virus, specifically by the AFSU strain. The remaining person was infected with a CRF-06cpx recombinant. Analysis of pairwise genetic distance among all PWID studied revealed an average of 3.1% sequence divergence, suggesting clonal introduction of the AFSU strain and/or constraints on sequence divergence. The HIV prevalence was less than 10% among MSM. All 17 sequences from HIV-infected MSM were found to be a clade B virus with a much higher average sequence diversity of 15.7%. These findings suggest two independent epidemics with little overlap between the two highest at-risk populations, which will require different HIV prevention approaches.

Aims Home-made preparation of heroin is common in countries of the former Soviet Union (FSU), and the addition of blood during its preparation and the use of contaminated syringes to distribute it may play a role in the rapid spread of HIV-1 among injecting drug users (IDUs). This study was designed to determine the viability of HIV-1 during these procedures. Setting Field observations of home-made opiate manufacture in four FSU countries were used to develop a consensus protocol to replicate manufacture in the laboratory that included the addition of human blood contaminated with HIV-1. Design and measurement Following the addition of HIV-1-contaminated blood during manufacture or storage, we attempted to recover viable HIV-1. The recovery was measured by propagation of the virus in stimulated white blood cells from uninfected donors. Findings In experiments in which HIV-1 contaminated blood was added during manufacture, no viable HIV-1 was recovered. In experiments in which chornaya was introduced into HIV-contaminated syringes, the percentage of syringes containing viable HIV-1 was reduced. The reduction appeared to be related to the interaction of HIV-1 contaminated blood with a component of the poppies. While HIV-contaminated syringes used to dispense or inject home-made opiates might transmit HIV, the ability of chornaya to reduce HIV viability seems to make this route of transmission less efficient. Conclusions The epidemic of HIV-1 among IDUs in the FSU resulted more probably from recognized injection risk behaviors—including sharing syringes and drug solutions—than from opiate solutions harboring viable HIV-1.

The Russian HIV-1 epidemic has been driven by injection drug use. The objective was to determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. In 2002 a cohort of 520 injection drug users (IDU) in St Petersburg Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. Most enrolled subjects were young male living at home educated heroin users and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis psychostimulant use especially frequent use three or more sex partners in the past 6 months and females selling sex were associated with HIV seroconversion. In the multivariate analysis psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately. (authors)

The relationships between commercial sex work, drug use, and sexually transmitted infections (STI) in St. Petersburg, Russia were assessed using qualitative research methods and an examination of existing research, surveillance and epidemiology data. The rapid assessment methodology included in-depth qualitative interviews with key informants, naturalistic observations of commercial sex work and drug use sites, geo-mapping, and a critical review of the available surveillance, epidemiology, and sociological data. Patterns of commercial sex work and drug use in St. Petersburg are described. The existing surveillance data attributes infections to injected drug use over and above any other risk category. However, examination of the clinic and epidemiology data suggests that HIV infection may be increasing fastest among groups that are acquiring HIV through sexual transmission. Targeted screening studies of STI and HIV morbidity among populations that are not included in the surveillance algorithm are needed, such as commercial sex workers, street youth, and the homeless. Sexual history taking to better characterize the proportion of cases that result from sex between male partners would also be helpful.

Two separate databases, one on Russian (n = 444) injection drug users (IDUs), and the other on U.S. IDUs (n = 241), were merged, and responses were compared. Results indicated that Russian IDUs perceived themselves to be at greater risk for HIV/AIDS based upon behaviors over the past 90 days. U.S. IDUs were more likely to be tested for HIV, report a negative HIV result, and know more people with HIV. U.S. IDUs consumed greater amounts of alcohol and marijuana, and made more alcohol/drug treatment attempts than Russian IDUs. Russian IDUs injected more frequently, although were more likely to recently use clean needles. Russian and U.S. IDUs responded significantly differently to eight AIDS knowledge questions. Eight condom attitude questions were asked of each group, and each revealed significantly different responses. Gender differences for Russian IDUs were also observed. There is a clear need to create culturally targeted sexual risk reduction interventions.

The previous studies of anti-HIV-1 humoral immune response have found the stable individual structural bias in the antibody production that reflects the changes in the immune functional network caused by HIV-1. The correlation between antigen structure, in particular the V3 domain of HIV-1, and the serum specificity to the structure remains unclear. To clarify the role of host individual factors in the serum specificity, we used the slightly modified HIV-1 serotyping methodological approach for the sera of the patients infected with HIV-1 with a different level of genetic similarity. Substantial discrepancy between serum specificities and antigen structure was found. Patients infected with HIV-1 carrying similar and identical V3 sequences had significantly different serum specificities. The opposite situation was often observed as well. The results of the study suggest that the influence of the V3 loop structure in the development of humoral immune response to the V3 loop is substantially modified in a patient-specific manner.

The purpose of this descriptive study was to compare young Russian NEP attenders (N = 209) and nonattenders (N = 207) on a multitude of dependent variables related to drug and sexual knowledge, attitudes, and behaviors. Questionnaire data found NEP attenders were more likely to be female, inject more frequently, use heroin heavily, be in long-term relationships, use clean needles, have more unprotected vaginal sex acts, and have drug-using friends with positive safer sex attitudes. Comparisons were also made between male and female NEP attenders, male NEP attenders and nonattenders, female NEP attenders and nonattenders, and male and female NEP nonattenders. Significant differences between those subgroups were found. A logistic regression was run to determine which variables served to predict NEP attendance. Four variables accounted for 17% of the variance and predicted NEP attendance in two thirds of the cases: safer sex attitudes of drug-using friends, heroin use, using new needles to inject, and relationship status.

The HIV-1 epidemic among injecting drug users (IDUs) in countries of the former Soviet Union (FSU) was caused mainly by two HIV-1 variants: subtype A and CRF03-AB. To date only three full-length HIV-I genomes from the FSU have been sequenced: one subtype A from Byelorussia and two CRF03-AB from Russia. We report the full-length genome cloning and analysis of two more HIV-1 strains from the FSU countries (98UA0116 of subtype A and 98BY10443 of CRF03-AB). Isolate 98UA0116 is the second cloned and sequenced full-length HIV-1 genome of subtype A lineage from the FSU, which may be a novel subsubtype within sub-type A. Isolate 98BY10443 is the third full-length HIV-1 genome of CRF03-AB in the world to be cloned and sequenced. Additionally, it is the first CRF03-AB strain discovered in Byelorussia. Cloned genomic sequences of the FSU HIV-1 isolates are being used for the development of a region-specific HIV-1 vaccine.

Over the last several years, Russia has experienced dramatic increases in rates of HIV and other sexually transmitted disease (STDs). This study examined HIV/AIDS knowledge, attitudes toward condoms, and sources of information about HIV in a sample of 200 male and 200 female Russian STD clinic patients. Study participants displayed substantial knowledge deficits concerning AIDS and HIV transmission. Superior knowledge was associated with younger age, greater education, positive attitudes toward condoms, having more sources of information about HIV/AIDS, and believing that the government is telling the truth about AIDS. More-positive attitudes toward condoms were associated with having a larger number of information sources, greater HIV/AIDS knowledge, and not being in a steady relationship. Many participants reported not trusting government and media sources of information concerning AIDS. Participants also reported concerns regarding the low quality and high cost of condoms in Russia. Results of the study suggest that interventions designed to increase knowledge and awareness of AIDS among Russians at high risk for HIV are urgently needed.

The purpose of this study was to establish the prevalence of high-risk sexual behaviors and drug-using behaviors in a large community sample of male and female injection drug users (IDUs) in St. Petersburg, Russia. This investigation used a data collection plan that systematically recruited a drug user sample from venues where IDUs were known to congregate and could be accessed. Surveys were completed by 239 IDUs (males = 139, females = 100), aged 13-25. Participants averaged 44 injections (range = 0-240) in the past 30 days, with heroin (70%) and heroin plus other drugs (20%) the most frequently used. Participants' mean age of first drug injecting was 17.6 years, 41% of participants regularly shared needles, most had multiple sexual partners (mean = 9.3 partners in the past 3 months), and 70% reported engaging in vaginal intercourse without condoms. Stepwise logistic regression showed that high-risk sexual behavior was predicted by being female, young, using heroin several times a month, and less negative attitudes toward using condoms. Effective HIV prevention efforts for IDUs in Russia must be tailored to their age, gender, drug use, and condom attitudes. These programs will also have to address the dual risk factors, unique to IDUs, of risky sexual behaviors and needle sharing. Without a rapid intervention response, Russia's HIV/AIDS crisis will soon turn catastrophic.

A phage peptide library was used to select peptides interacting with virus-neutralizing monoclonal antibodies (mAb) 2G12 which recognize a discontinuous surface epitope of HIV-1 gp120. With the published X-ray data, gp120 regions involved in the antigenic determinant were predicted. Binding with mAb 2G12 was ascribed to Thr297, Phe383, Tyr384, Arg419, Ile240, Thr415, Leu416, Pro417, Lys421, and Trp112. Though distant in the gp120 sequence, these residues are close in space and form the 2G12 epitope on the gp120 surface.

The origin of novel genes is one of the major events in genome evolution. The phenomenon of the origin of novel genes is now well established. Novel genes may originate from pre-existing genes or de novo. It appears that gene duplication, exon shuffling, and de novo origin are the most fundamental modes, or principles, of the origin of novel genes. Transposons and endogenous retroviruses also participate in gene origin and genome evolution. There are many more molecular mechanisms that participate in the process of gene origin – several molecular mechanisms for each of the major modes of gene origin, and their combinations. The general conclusion that authors make after considering different principles and mechanisms of the origin of novel genes is that this process is frequent, ongoing and widespread. The emerging picture is that genomes are plastic, evolving entities.

A synthesis of evolutionary biology and the health sciences is emerging. New disciplines – Darwinian medicine, evolutionary epidemiology and evolutionary oncology – attempt to apply the evolutionary approach to their corresponding traditional areas of research. Darwinian medicine focuses more on the individual patient whereas evolutionary epidemiology focuses on the spread of diseases. From the standpoint of Darwinian medicine, many diseases and health conditions have evolutionary origin. For example, senescence may be a result of the selection of traits that are advantageous at the early ages but are associated with adverse effects later in life. Evolutionary epidemiology assesses how traditional epidemiological characteristics such as lethality, illness, transmission rates, virulence and prevalence of infection change over time in the process of co-evolution of parasites and their hosts. The topic of this book is evolutionary oncology, i.e. evolution of tumor-bearing organisms and the role of tumors in evolution of organisms.

While Darwinian medicine and evolutionary epidemiology are looking for advantages which evolutionary biology could provide to the health sciences and medicine, evolutionary biology is interested in what role different pathologies could play in evolution. There are examples of pathogens and pathologies which have evolutionary importance. The most outstanding of those is mutational process, which governs the evolution, on one side, and generates various molecular diseases, on the other. I call this dualism “evolution vs. pathology paradox” of mutations.

There is a list of tumors that have played a role in evolution. This list includes the nitrogen-fixing root nodules of legumes; melanomatous cells that gave rise to macromelanophores in Xiphophorus fishes; benign tumors which after artificial selection gave rise to the hood of goldfishes; malignant papillomatosis which gave rise to symbiovilli in the stomach of voles; and the tumor-like organ, eutherian placenta. The “evolution vs. pathology paradox” may exist for tumors. Tumors could be considered as mutations at the multicellular level. On one hand, tumor processes may lead to various malignancies which may be harmful to individual organisms. On the other hand, tumor processes provide excess cell masses with high biosynthetic potential, and this may be used in progressive evolution for generation of new cell types, tissues and organs if organisms with tumors survive long enough to leave the progeny.

The whole content of this book, including our own experimental data, supports the positive evolutionary role of tumors and the hypothesis of evolution by tumor neofunctionalization. The additional supporting lines of evidence include positive selection of many tumor-related genes in primate lineage; differential expression of human endogenous retroviruses (HERVs) in many human tumors; expression of evolutionarily novel and positively selected genes in the placenta, a tumor-like organ; and evidence of a connection of anti-cancer selection with developmental and evolutionary constraints that supports the concept of the positive role of tumors in progressive evolution.

Tumors that might play the role in evolution include hereditary tumors; fetal, neonatal and infantile tumors; benign tumors, carcinomas in situ and pseudodiseases; tumors at the early and intermediate stages of progression; tumors that spontaneously regress through differentiation; and dormant tumors or tumors in the state of equilibrium. However, malignant tumors at the late stages of progression cannot play such a role, although cases of spontaneous regression of malignant tumors are described and placenta, a tumor-like organ in eutherians, has invasive potential.

There are features of tumors that could be used in evolution: many genes usually inactive in normal cells are activated in tumor cells; tumor cells can differentiate with concomitant loss of malignancy; tumors generate extra cell masses which are functionally not necessary for the organism and could be used as a building material for new cell types, tissues and organs; tumors have features of atypical tissues/organs and may participate in morphogenetic processes. The ability of tumor cells to differentiate with concomitant loss of malignancy, in combination with their ability to express genes that are not expressed in normal tissues and with other tumor features may result in the emergence of new cell types, tissues and organs in evolution.

Background The majority of HIV-infected individuals requiring antiretroviral therapy (ART) in Russia are Injection Drug Users (IDU). Substitution therapy used as part of a comprehensive harm reduction program is unavailable in Russia. Past data shows that only 16% of IDU receiving substance abuse treatment completed the course without relapse, and only 40% of IDU on ART remained on treatment at 6 months. Our goal was to determine if it was feasible to improve these historic outcomes by adding intensive case management (ICM) to the substance abuse and ART treatment programs for IDU. Methods IDU starting ART and able to involve a “supporter” who would assist in their treatment plan were enrolled. ICM included opiate detoxification, bi-monthly contact and counseling with the case, weekly group sessions, monthly contact with the “supporter” and home visits as needed. Full follow- up (FFU) was 8 months. Stata v10 (College Station, TX) was used for all analysis. Descriptive statistics were calculated for all baseline demographic variables, baseline and follow-up CD4 count, and viral load. Median baseline and follow-up CD4 counts and RNA levels were compared using the Kruskal-Wallis test. The proportion of participants with RNA

The available data indicate the convergence of tumorigenic and embryonic signaling pathways. Canonical signaling pathways are fundamentally involved in the development of both normal organs and tumors of various histogenesis, i.e. atypical organs. Normal stem cells and tumor stem cells are regulated by common networks that include protooncogenes and tumor suppressors. Tumors are a disease of differentiation: the overproduction of undifferentiated cells causes tumors; tumors are the result of the loss/mutation of differentiation products, and the loss of malignancy is connected with the presence of differentiation products. The relationship between tumors and differentiation is dynamic. Tissue-specific functions are connected with their corresponding genes/differentiation products, and the loss of functions (e.g. due to mutations) is connected with tumors. The lack or disruption of a functional regulatory feedback loop may be the cause of tumors. On the other hand, the role of functional regulatory feedbacks appears as determinative in the differentiation of tumors when it occurs, and could be used in the evolutionary origin of new cell types/tissues/organs from tumors. This evidence suggests the fundamental connection of tumors and embryonic development and the possibility that tumors might participate in the evolution of ontogenesis.

The origin of evolutionarily novel genes is connected with the origin and evolution of the novel organismal functions and the increase in morphological complexity of multicellular organisms. Novel genes acquire new or altered functions. Different modes of gene origin – gene duplication, exon shuffling and de novo origin – are connected with somewhat different ways of acquisition of new functions. The duplicate genes can acquire new functions by neofunctionalization, i.e. the origin of an entirely new function, and by subfunctionalization, when each of two genes retains only a subset of original functions. Exon shuffling leads to novel combinations of already existing functions. De novo–originated genes should have some novel, previously non-existent functions. These functions fit into developmental or terminal differentiation classes of functions. Correlation of phylogenetic differences at later ontogenetic stages with the expression of newly evolved genes and other evidence support the role of novel genes in the origin of evolutionary innovations and morphological novelties. The extra cell masses are needed for the expression of novel genes and the origin of innovations.