HIV infection in Russia in 1998

The statistic information about the distribution of HIV-infected persons in 1998 in different regions of Russian Federation was presented 3169 new cases of HIV-infected persons of Russia registered by 11.5 months in 1998. This are only 82.2% cases in comparison of cases (3856) which registered in 1997. The total number HIV-infected persons registered by 1st of January 1987-16th of November 1998 was 10,193, among them 431 children. 112 children were infected during period of mother's pregnancy and parturitions.     

The epidemic situation in relation to HIV infection in the Volga River region

1,036 HIV-infected persons were detected in the area by March 1, 1998; of these, 552 persons were detected in Nizhny Novgorod Province and 364 persons in Saratov Province. For all that at different periods 150 HIV-infected detainees were kept in the pretrial detention prisons of Nizhny Novgorod Province and 60 HIV-infected detainees, in the pretrial detention prisons of Saratov Province. Some measures permitting the prevention of further increase in the occurrence of HIV infection in the region are proposed.     

Emergency measures to control the spread of diseases caused by the human immunodeficiency virus

Since the middle of 1996 the growth of HIV-infected persons and AIDS morbidity are registered in Russia. In 1997 4,300 new cases of HIV infection were registered, which exceeded 1.6 times the total number of cases for the period of 1987-1996. The highest morbidity rate was observed in the cities of the European part of Russia: Kaliningrad (west), Krasnodar and Rostov-on-Don (south), Nizhny Novgorod and Moscow (center). AIDS patients and HIV-infected persons were registered in 73 out of 89 regions of the country. 90% of HIV-infected persons were drug users in 1997. In 1992-1997 the number of drug addicts increased 3.5 fold and young women in 1987-1997, 6.5 fold. 71 HIV-infected children were registered were born from HIV-infected mothers at present time. The article deals with the main provisions of the federal laws aimed at the prevention of the spread of HIV infection in Russia and characterizes scientific research on AIDS. Evidence is presented that the early detection of HIV-infected persons, as well as rendering timely medical and social assistance to such persons, makes it possible to increase their mean survival time and check the spread of human immunodeficiency virus.     

Protists as opportunistic pathogens: public health impact in the 1990s and beyond

Protist organisms (protozoa and fungi) have become increasingly prominent as opportunistic pathogens among persons infected with human immunodeficiency virus (HIV) and among organ transplant recipients--two immunocompromised populations that have increased dramatically in the past two decades. Pneumocystis carinii pneumonia continues to be the most common serious opportunistic infection (OI) among HIV-infected persons in the United States, occurring frequently among persons not previously receiving medical care. Toxoplasmosis, cryptococcosis, cryptosporidiosis, and isosporiasis occur frequently in HIV-infected persons in the developing world. Candidiasis and aspergillosis are common OIs in organ transplant recipients. As these populations of immunosuppressed patients continue to expand worldwide new OIs caused by protist pathogens are likely to emerge.     

The detection of viral hepatitis markers in HIV-infected patients

The determination of markers of virus hepatitides B, C and D in 63 registered HIV-infected persons was made. The use of Russian and foreign EIA systems permitted the detection of markers of virus hepatitides 30.1% of HIV-infected persons, including 26.3% of children. Markers of hepatitis B virus were found to occur in children and adults with the same frequency. Out of 65 persons registered in the Center, 3 persons (4.6%) were drug addicts; of these, 2 were found to have antibodies to antigens of hepatitis viruses. Such persons constituted 3.8% of the total number of HIV-infected persons. Among 8 newly detected and registered HIV-infected adults, 2 were found to have antibodies to hepatitis B virus (of these, 1 used drugs intravenously).     

The determinants of the spread of HIV among injection drug addicts in Ukraine

The main tendencies in the development of drug addiction in the Ukraine, the dynamics of the spread of HIV among drug addicts introducing drugs intravenously, epidemiological data on HIV, AIDS and drug addiction, as well as prognoses on the development of HIV infection are presented. Since 1995 the number of HIV-infected persons grew 34-fold, the number of cases of HIV infection resulting from the intravenous use drugs rose to 70% simultaneously with the rise (about 34-fold) of the number of persons infected with HIV through sexual contacts (about 13 fold). In 1996-1997 such tendency increased. On the whole, the proportion of drug addicts introducing drugs by intravenous injection was 83% in the Ukraine. By April 1, 1998, official registration covered 18,800 HIV-infected persons, including 270 foreign nationals, as well as 499 AIDS patients, including 487 Ukrainian citizens, among them 28 children. Out of 18,800 HIV-infected persons, 78.3% were drug addicts, most of them young people aged 15-30 years; about 18% were young people under 20 years of age, 80% being males. According to the model the rapid spread of HIV from the group of drug addicts to the heterosexual population, the total number of HIV-infected persons reaching 1,500,000 is expected in the country by 2014.     

HIV Infection and the Epidemiology of Invasive Pneumococcal Disease (IPD) in South African Adults and Older Children Prior to the Introduction of a Pneumococcal Conjugate Vaccine (PCV)

Introduction

Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV) programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD) in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use.

Methods

National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES) hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI) in 2009.

Results

In South Africa, from 2003–2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734) of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000), with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190). HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV) than HIV-infected persons (39% (210/544) vs. 19% (790/4190), p<0.001). During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7–1.1).

Conclusion

Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection) for pneumococcal vaccination. These data describe the epidemiology of IPD amongst HIV-infected and -uninfected adults during the pre-PCV era and provide a robust baseline to calculate the indirect effect of PCV in future studies.     

Epidemic process of HIV-infection and HIV-associated tuberculosis in Primorsky region

The article provides data on HIV-infection prevalence in Primorsky region as well as on characteristics of HIV-infection epidemic process, distribution of HIV-infected persons by sex, age, routes and factors of transmission. Rise of HIV-associated tuberculosis incidence is registered in Primorsky region in recent years. HIV-infected persons have increased risk of tuberculosis progression. Prognosis for HIV-infection and HIV-associated tuberculosis incidence for the next years was done.     

The development of HIV infection in the Far-Eastern region of the Russian Federation

By May 18, 1998, 108 HIV-infected persons were registered in the Far-Eastern region. In recent years young people using narcotic drugs were involved in the epidemic process. The sources of the infection were mainly migrants arriving to the Far East from the Ukraine. HIV-infected persons also were registered in settlements lying north of the Arctic Circle.     

HIV infection in pregnant women in Chelyabinsk

Data on HIV infection in pregnant women in Chelyabinsk are presented. Starting from 1999, a considerable rise in the number of HIV-infected persons was registered in this city. The social and epidemiological characteristics of HIV-infected pregnant women, as well as the main routes and factors of the infective agent transmission, are given. Relationship between the spread of HIV-infection and drug addiction is revealed. The occurrence of different opportunistic infections in HIV-infected pregnant women is determined.     

Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals

Background

Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV.

Methodology/Principal Findings

This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals.

Conclusions/Significance

LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our results suggest that microbial translocation may be associated with innate and adaptive immune dysfunction in untreated HIV infection.     

A strategy for the control of HIV infection and viral hepatitides against the background of the narcotic abuse epidemic

The presence of the epidemic of drug addiction in the Russian Federation is stated: for the recent 10 years the number of drug addicts increased 3.5-fold. The questioning of several thousand drug addicts has revealed that 60% of them have hepatitis B, 80% have hepatitis C, 10% have syphilis. The strategy of controlling HIV infection among drug addicts is proposed. It includes, in the first place, the prevention of the secondary infection from HIV-infected addicts; in the second place, the detection of HIV-infected persons in groups of drug addicts, difficult to establish contacts with; in the third place, the primary prophylaxis within the program "Harm reduction" in the most susceptible groups of drug addicts. The thesis that the prevention of HIV infection must become the prevention of drug addiction by rendering multi-stage assistance to HIV-infected persons, including mainly drug addicts, is substantiated.     

An analysis of an outbreak of HIV infection in the city of Svetlogorsk, the Republic of Byelarus, among persons using injected narcotics

The examination of all persons suspected in the use narcotics (including suppliers and vendors of drugs) in Svetlogorsk (Belarus) for the presence of antibodies to HIV revealed 811 cases of HIV infection, i.e. 1% of the whole population was found to be infected by HIV. More than 90% of all HIV-infected persons were drug addicts introducing narcotic intravenously; young people aged 18 to 29 years constituted 81% (of these, 76% were males and 24% were females). The rapid spread of HIV was caused by the use of a ready-made HIV-infected drug which had been supplied for sale and could have been infected in the process of manufacture or packing.     

Poliovirus excretion in Guatemalan adults and children with HIV infection and children with cancer.

More than 20 patients with persistent poliovirus infections have been identified and reported to WHO. To date, almost all of these patients have had B-cell immune deficiency disorders. Since there are limited data on patients with HIV infection who have received oral poliovirus vaccine (OPV), we studied adults and children to determine if persons with acquired immunodeficiency due to HIV infection or cancer chemotherapy in a developing country setting had prolonged excretion of polioviruses. Stool samples from 94 HIV-infected children and 101 adults and 50 children surviving cancer in Guatemala City were cultured for polioviruses. No polioviruses were detected in any of the 195 persons with HIV infection or the 50 with cancer. The evidence from this and other studies indicates that the persistent poliovirus excretion in HIV-infected individuals is an unlikely event.     

Impaired naive and memory B-cell responsiveness to TLR9 stimulation in human immunodeficiency virus infection

Toll-like receptor 9 (TLR9) agonists such as unmethylated bacterial CpG DNAs activate B lymphocytes directly, potentially influencing their function and homeostasis. To assess B-cell responsiveness to TLR9 agonists in human immunodeficiency virus (HIV) disease, we examined the ability of naive and memory B cells to proliferation and to increase surface expression of CD80 in response to CpG oligonucleotides (ODN). CpG ODN induced expression of CD80 similarly in B cells from HIV-infected persons and from healthy controls. In contrast, proliferation responses to CpG ODN were markedly impaired in both naive and memory B-cell subsets from HIV-infected persons. Naive B-cell proliferation defects were related to plasma HIV RNA and, among memory B cells, to the frequencies of CD21-negative cells. Importantly, TLR9 mRNA levels were significantly diminished in freshly prepared naive B cells and especially so in memory B cells from HIV-positive viremic donors, suggesting a possible underlying mechanism for the observed functional impairments. Dose-response studies indicated that optimal induction of CD80 expression was achieved with much lower concentrations of CpG ODN than optimal induction of proliferation. We propose that the relatively low threshold of activation that is required for CD80 induction by CpG ODN might explain the preservation of this response in B cells from HIV-infected persons despite diminished TLR9 expression. Impaired responsiveness to TLR9 agonists may contribute to defects in humoral immunity in HIV infection.     

Decreased IL-7 Responsiveness Is Related to Oxidative Stress in HIV Disease

HIV disease results in decreased IL-7 receptor expression and IL-7 responsiveness in T cells. To explore mechanisms of these deficiencies, we compared CD127 expression and IL-7 induction of P-STAT5 in T cells from HIV-infected persons with serum concentrations of cytokines (IL-7, IL-6 and IL-15), markers of microbial translocation (sCD14 and LPS), and with an indicator of oxidative stress (malondialdehyde (MDA) adducts). CD127 expression was directly related to IL-7 responsiveness in most CD8+ T cell subsets but not in CD4+ T cells from HIV-infected persons. MDA adducts were increased in serum of HIV-infected patients and were inversely related to IL-7 responsiveness in CD8+ T cells and in central memory CD4+ T cells. Incubation of T cells from healthy controls with hydrogen peroxide resulted in impairments in IL-7 induction of P-STAT5. These findings suggest that oxidative stress that is characteristic of HIV disease could contribute to impairments in IL-7 responsiveness and disrupt T cell homeostasis.     

Point prevalence, microbiology and antifungal susceptibility patterns of oral Candida isolates colonizing or infecting Mexican HIV/AIDS patients and healthy persons

We have conducted a longitudinal study over a 3-year period to address the point prevalence, microbiological characteristics and antifungal susceptibility patterns of yeast isolates colonizing or infecting the oral cavities of 111 HIV-infected (51 adults, 60 children) and 201 non HIV-infected (109 adults, 92 children) Mexican persons. Regarding the epidemiology of oral candidiasis, Candida albicans was the most frequent species isolated. Seventy-one out of 85 isolates from colonized persons were C. albicans (83.5%), 27 isolates of them were from HIV-infected children and 44 from non HIV-infected patients. Sixty-two isolates belonged to serotype A which was the most prevalent serotype of C. albicans. Non-albicans species (Candida glabrata, Candida tropicalis and Candida parapsilosis, and Saccharomyces cerevisiae) were isolated from 16.5% of colonized patients and from 38.5% patients with candidiasis or Candida-related lesions. There were nine episodes of infection or colonization by at least 2 different yeast species. In the case of HIV/AIDS patients, it was determined that yeast carriage was not associated with the number of CD4+ cells or the viral load, but HAART reduced the prevalence of oral candidiasis. Overall, most patients harbored strains in vitro susceptible to fluconazole, however 10.8% of the yeasts were resistant to one or more azole antifungal agents and 29% were intermediate susceptible to them. On the contrary, 5-fluorocytosine was very active against all isolates tested, and amphotericin B was active against 97.9% of them.     

HIV/AIDS among Inmates of and Releasees from US Correctional Facilities, 2006: Declining Share of Epidemic but Persistent Public Health Opportunity

Because certain groups at high risk for HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) come together in correctional facilities, seroprevalence was high early in the epidemic. The share of the HIV/AIDS epidemic borne by inmates of and persons released from jails and prisons in the United States (US) in 1997 was estimated in a previous paper. While the number of inmates and releasees has risen, their HIV seroprevalence rates have fallen. We sought to determine if the share of HIV/AIDS borne by inmates and releasees in the US decreased between 1997 and 2006. We created a new model of population flow in and out of correctional facilities to estimate the number of persons released in 1997 and 2006. In 1997, approximately one in five of all HIV-infected Americans was among the 7.3 million who left a correctional facility that year. Nine years later, only one in seven (14%) of infected Americans was among the 9.1 million leaving, a 29.3% decline in the share. For black and Hispanic males, two demographic groups with heightened incarceration rates, recently released inmates comprise roughly one in five of those groups'' total HIV-infected persons, a figure similar to the proportion borne by the correctional population as a whole in 1997. Decreasing HIV seroprevalence among those admitted to jails and prisons, prolonged survival and aging of the US population with HIV/AIDS beyond the crime-prone years, and success with discharge planning programs targeting HIV-infected prisoners could explain the declining concentration of the epidemic among correctional populations. Meanwhile, the number of persons with HIV/AIDS leaving correctional facilities remains virtually identical. Jails and prisons continue to be potent targets for public health interventions. The fluid nature of incarcerated populations ensures that effective interventions will be felt not only in correctional facilities but also in communities to which releasees return.     

Novel HIV-1 MiRNAs Stimulate TNFα Release in Human Macrophages via TLR8 Signaling Pathway

Purpose

To determine whether HIV-1 produces microRNAs and elucidate whether these miRNAs can induce inflammatory response in macrophages (independent of the conventional miRNA function in RNA interference) leading to chronic immune activation.

Methods

Using sensitive quantitative Real Time RT-PCR and sequencing, we detected novel HIV-derived miRNAs in the sera of HIV+ persons, and associated with exosomes. Release of TNFα by macrophages challenged with HIV miRNAs was measured by ELISA.

Results

HIV infection of primary alveolar macrophages produced elevated levels of viral microRNAs vmiR88, vmiR99 and vmiR-TAR in cell extracts and in exosome preparations from conditioned medium. Furthermore, these miRNAs were also detected in exosome fraction of sera from HIV-infected persons. Importantly, vmiR88 and vmiR99 (but not vmiR-TAR) stimulated human macrophage TNFα release, which is dependent on macrophage TLR8 expression. These data support a potential role for HIV-derived vmiRNAs released from infected macrophages as contributing to chronic immune activation in HIV-infected persons, and may represent a novel therapeutic target to limit AIDS pathogenesis.

Conclusion

Novel HIV vmiR88 and vmiR99 are present in the systemic circulation of HIV+ persons and could exhibit biological function (independent of gene silencing) as ligands for TLR8 signaling that promote macrophage TNFα release, and may contribute to chronic immune activation. Targeting novel HIV-derived miRNAs may represent a therapeutic strategy to limit chronic immune activation and AIDS progression.