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
X2 = 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.
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.
In order to be inherited in progeny generations, novel genes should originate in germ cells. Here, we suggest that the testes may play a special “catalyst” role in the birth and evolution of new genes. Cancer/testis antigen encoding genes (CT genes) are predominantly expressed both in testes and in a variety of tumors. By the criteria of evolutionary novelty, the CT genes are, indeed, novel genes. We performed homology searches for sequences similar to human CT in various animals and established that most of the CT genes are either found in humans only or are relatively recent in their origin. A majority of all human CT genes originated during or after the origin of Eutheria. These results suggest relatively recent origin of human CT genes and align with the hypothesis of the special role of the testes in the evolution of the gene families.
Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisition, suggesting that this region is associated with infection as well as disease progression. Our study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment. In addition, our results also indicate the possibility of using genetic markers as HIV disease progression indicators in sub-Saharan Africans to prioritize fast progressors for antiretroviral treatment.
The aim of the project was to study human immunodeficiency virus (HIV) incidence, sociodemographic and behavioral correlates of HIV acquisition among injection drug users (IDUs).A total of 717 IDUs were recruited, tested, and counseled for HIV-1; 466 HIV-negative participants were enrolled and followed-up at 6 and 12 months. Sociodemographic and behavioral data were collected during each study visit. The association of sociodemographic and behavioral factors to HIV-1 incidence was assessed.During the 9-month recruitment period, 717 IDUs were screened and 466 participants were enrolled. HIV-1 prevalence at baseline was 35%. Most enrolled subjects were young (median age 30), male (75%), injected heroin in the previous 3 months (86%), about 50% had shared syringes and other paraphernalia, and 44% had unprotected sex in the last month. The retention rate at the 12-month follow-up was 72% and the adjusted retention rate was 88%. The HIV incidence rate was 7.2/100 person-years. HIV incidence was significantly associated with specific drug risk behaviors, including injecting the mixture of heroin and psychostimulants, the frequency of injecting in groups with other people, and having more drug dealers.The St Petersburg IDUs cohort demonstrates one of the highest HIV incidence rates in the world. In 2004 to 2006, the HIV incidence was 4.5, in 2005 to 2007—19.6, and in 2008 to 2009—7.2/100 person-years. The peak of HIV epidemic among IDUs in St Petersburg, as determined by 3 independent cohort studies, was in 2006 to 2007. Interventions targeting IDUs with long experience of heroin injection and high levels of injection risk behaviors are urgently needed.
We consider the Case 1 interval censoring approach for right-censored survival data. An important feature of the model is that right-censored event times are not observed exactly, but at some inspection times. The model covers as particular cases right-censored data, current status data, and life table survival data with a single inspection time.We discuss the nonparametric estimation approach and consider three nonparametric estimators for the survival function of failure time: maximum likelihood, pseudolikelihood, and the naïve estimator. We establish strong consistency of the estimators with the L 1 rate of convergence.Simulation results confirm consistency of the estimators.
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