The effect of new drug approvals on HIV mortality in the US, 1987–1998

After increasing steadily from 1987 to 1995, the number of US deaths caused by human immunodeficiency virus (HIV) declined sharply from 1995 to 1998. We analyse aggregate data to consider the hypothesis that this decline was due to a rapid increase in the number of drugs available to treat HIV. The evidence suggests that new drugs played a key role in the post-1995 decline in HIV mortality. The annual number of HIV deaths is estimated to have been reduced by over 6000, on average, by an additional HIV drug approval. The social return to HIV drug innovation appears to be extremely large.     

Clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs: comparison with homosexual seroconverters and infected and non-infected intravenous drug misusers.

OBJECTIVE--To study the clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs. DESIGN--Case-control study in cohorts of drug misusers and homosexual men. SETTING--Outpatient clinic, Municipal Health Service, Amsterdam. SUBJECTS--Misusers of intravenous drugs from our prospective cohort who seroconverted for HIV. Controls were drug users positive for HIV, drug users negative for HIV, and homosexual men who had seroconverted. RESULTS--Five out of 18 (28%) drug users were admitted to hospital with bacterial pneumonia in the four to six months between their last visit at which they were HIV negative and their first visit when they were HIV positive. For comparison none of the 27 homosexual men who seroconverted for HIV, three out of 177 (2%) drug users negative for HIV, and 10 out of 112 (9%) drug users positive for HIV reported bacterial pneumonia. One out of the 18 drug users who seroconverted suffered from oesophageal candidiasis at the time of seroconversion. Other clinical symptoms did not differ between drug users who seroconverted and those who remained negative for HIV, probably due to the high background morbidity among the drug users. CONCLUSIONS--Seroconversion to HIV-1 among intravenous drug misusers is associated with bacterial pneumonia. Those drug users with previously negative test results for HIV who are admitted to hospital for bacterial pneumonia should be tested to detect primary infection with HIV-1.     

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.     

The results of sentinel epidemiological surveillance on the level of HIV prevalence among injection narcotic abusers in the city of Poltava

The sentinel epidemiological surveillance on the level of spread of HIV infection among injecting drug users in Poltava, taking part in the program of harm reduction, was carried out. The results of the surveillance revealed that the level of HIV infection among drug users was 37.8%, the level of HIV infection among females being higher than that among males. These data indicate that the level of HIV infection rises with the increase of age and the time of drug consumption. Still in the age group of 30 years and older and among drug addicts using drugs for 7 years and longer the lowest level of HIV infection was noted.     

Assessing the effects of drug misuse on HIV/AIDS prevalence

Drug misuse (injecting drug users-IDU) has been recognized to have a significant effect on the spread of HIV/AIDS epidemic. A deterministic model to assess the contribution of drug misuse and sex in the spread of HIV/AIDS is investigated. The threshold parameters of the model are determined and stabilities are analysed. Analysis of the reproduction number has shown that increase in drug misuse results in an increase in HIV infections. Furthermore, numerical simulations of the model show that drug misuse enhances HIV transmission and progression to AIDS. Thus, in a population with intravenous drug users, advocating for safe sex alone will not be enough to control the HIV/AIDS epidemic.     

Factors influencing the emergence and spread of HIV drug resistance arising from rollout of antiretroviral pre-exposure prophylaxis (PrEP)

Background

The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.

Methodology

A model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.

Principal Findings

Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%–12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.

Conclusions

Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.     

Discrimination against people with HIV and AIDS in Poland.

The recent increase in HIV seroprevalence in Poland, particularly among injecting drug users, has been accompanied by widespread discrimination against people affected by HIV and AIDS. As in other countries, this discrimination may be attributed to a large extent to fear and ignorance about HIV and AIDS together with pre-existing prejudices against the people who are most commonly associated with the epidemic. In Poland extreme hostility towards drug users combined with the powerful influence of a traditional Catholic church have so far impeded effective education about HIV and AIDS and anti-discrimination strategies.     

Human immunodeficiency virus and drug misuse: the Edinburgh experience.

During 1985 many drug abusers who lived in Edinburgh were found to be infected with the human immunodeficiency virus (HIV). As a result an alternative counselling and screening clinic for testing for antibodies to HIV was established for use by drug abusers. Four hundred and forty one patients were counselled in the first year, and over 60% were either drug abusers or their sexual contacts. One hundred and fourteen (26%) patients were positive for HIV antibody, and 100 (88%) of these were current or former drug abusers. The HIV seropositivity rate in drug abusers was 52% but was only 7% in their sexual contacts. Services were provided for these people as well as counselling before and after the test. The cost of this counselling service for the first year was 27,000 pounds or 61.22 pounds per patient. The unexpected mobility of 23% of the Edinburgh drug abusers, particularly to other areas of Britain, suggests that similar services need to be set up elsewhere.     

Coinfection alters the playing field: herpesviruses induce acyclovir to inhibit HIV

The antiherpes drug acyclovir was found to inhibit HIV following its phosphorylation by human herpesviruses, providing a hypothesis to explain the observed beneficial effects of acyclovir therapy on HIV viral load and HIV disease progression. This report underscores the importance of studying HIV in the context of microbial copathogens.     

Injection drug use and HIV/AIDS transmission in China

After nearly three decades of being virtually drug free, use of heroin and other illicit drugs has re-emerged in China as a major public health problem. One result is that drug abuse, particularly heroin injection, has come to play a predominant role in fueling China's AIDS epidemic. The first outbreak of HIV among China's IDUs was reported in the border area of Yunnan province between China and Myanmar where drug trafficking is heavy. Since then drug-related HIV has spread to all 31 provinces, autonomous regions and municipalities. This paper provides an overview to HIV/AIDS transmission through injection drug use in China. It begins with a brief history of the illicit drug trade in China, followed by a discussion of the emergence of drug related AIDS, and a profile of drug users and their sexual partners who have contracted the virus or who are vulnerable to infection. It ends by summarizing three national strategies being used by China to address both drug use and AIDS as major health threats.     

Development of HIV infection epidemic among intravenous drug users in the Sverdlovsky region

The Sverdlovsky region takes the fourth place among the 89 subjects of the Russian Federation by the number of registered cases of HIV infection. Drug addiction has reached an excessive scale in this region: according to the data of express evaluation carried out by the Regional Narcological Hospital and the Regional AIDS Center, not less than 7-8% of persons aged 15-30 years constantly use injection drugs. The large-scale epidemic of injection drug addiction has led to the rapid spread of HIV among addicts. The first penetration of HIV into this population took place in 1996 and, starting from the year 2000, rapid, development of the epidemic began, taking the character of an avalanche. The peak of new cases of HIV infection fell on 2001 (9,230 cases were registered). The concentrated stage of the epidemic development is observed in the region at present, the prevalence of HIV infection among drug addicts being 13.8%. Children born from HIV-infected drug addicted mothers now represent a new risk group due to great difficulties in the prophylaxis of the vertical virus transmission.     

Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV.

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.     

Antiretroviral drug resistance mutations sustain or enhance CTL recognition of common HIV-1 Pol epitopes

Antiretroviral drug resistance and escape from CTL are major obstacles to effective control of HIV replication. To investigate the possibility of combining drug and immune-based selective pressures against HIV, we studied the effects of antiretroviral drug resistance mutations on CTL recognition of five HIV-1 Pol epitopes presented by common HLA molecules. We found that these common drug resistance mutations sustain or even enhance the antigenicity and immunogenicity of HIV-1 Pol CTL epitopes. Variable patterns of cross-reactive and selective recognition of wild-type and corresponding variant epitopes demonstrate a relatively diverse population of CD8(+) T cells reactive against these epitopes. Variant peptides with multiple drug resistance mutations still sustained CTL recognition, and some HIV-infected individuals demonstrated strong CD8(+) T cell responses against multiple CTL epitopes incorporating drug resistance mutations. Selective reactivity against variant peptides with drug resistance mutations reflected ongoing or previous exposure to the indicated drug, but was not dependent upon the predominance of the mutated sequence in endogenous virus. The frequency and diversity of CTL reactivity against the variant peptides incorporating drug resistance mutations and the ability of these peptides to activate and expand CTL precursors in vitro indicate a significant functional interface between the immune system and antiretroviral therapy. Thus, drug-resistant variants of HIV are susceptible to immune selective pressure that could be applied to combat transmission or emergence of antiretroviral drug-resistant HIV strains and to enhance the immune response against HIV.     

Epidemic human immunodeficiency virus (HIV) infection among intravenous drug users (IVDU)

Human immunodeficiency virus (HIV) infection is epidemic among intravenous drug users (IVDU), particularly in the northeastern United States. IVDU are playing a critical role in the spread of HIV by infecting their heterosexual partners and children, as well as their needle-sharing partners. The epidemiology of HIV infection among IVDU is reviewed here, including a compilation of seroprevalence data. Relevant determinants of the future spread of HIV among IVDU are discussed, including the major risk factors for HIV seropositivity, the modes of HIV transmission, and aspects of the natural history of HIV infection in IVDU. The public health policy implications of these issues include the need for education of adolescents and the general public about the risks of drug injection and heterosexual intercourse with IVDU, as well as motivation of IVDU to stop injecting, never share injection paraphernalia, or, at least, clean needles effectively.     

HIV as a surrogate marker for drug use: A re-analysis of the San Francisco Men's Health Study

Our analysis of drug use and morbidity data from a cohort of 1034 men yields the following results: 1) HIV infection is a strong indicator of drug use — HIV-positive respondents reported an average lifetime dose of recreational drugs (excluding marijuana) 2.3 times higher than HIV-negative respondents. 2) Homosexuality is a strong indicator of drug use — homosexual respondents reported an average lifetime dose 2.0 times higher than heterosexual respondents. 3) The incidence of AIDS-defining diseases was not limited to respondents infected with HIV, but was almost completely limited (98%) to respondents who reported using drugs. We also address a previous report (Ascheret al., 1993) that was based on the same database and purported to show that HIV alone correlates with the development of AIDS. Specifically, we show that the relationship between HIV infection and CD4+ T Cell loss is weaker than reported by Ascheret al., and provides little evidence for a causative relationship. These results support the hypothesis that long-term, habitual drug use can cause the conditions known as AIDS (independent of the presence of HIV), and refute the hypothesis that HIV alone causes these conditions independent of drug use.     

HIV behind Bars: Human Immunodeficiency Virus Cluster Analysis and Drug Resistance in a Reference Correctional Unit from Southern Brazil

People deprived of liberty in prisons are at higher risk of infection by the human immunodeficiency virus (HIV) due to their increased exposure through intravenous drug use, unprotected sexual activity, tattooing in prison and blood exposure in fights and rebellions. Yet, the contribution of intramural HIV transmission to the epidemic is scarcely known, especially in low- and middle-income settings. In this study, we surveyed 1,667 inmates incarcerated at Presídio Central de Porto Alegre, located in southern Brazil, for HIV infection and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667). Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV transmission clusters and drug resistance within the facility with the use of molecular and phylogenetic techniques. The molecular epidemiology of HIV-1 subtypes observed was similar to the one reported for the general population in southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and unique BC recombinants. In particular, the high rate (24%) of URF_BC found here may reflect multiple exposures of the population investigated to HIV infection. We failed to find HIV-infected inmates sharing transmission clusters with each other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high rates of HIV primary and secondary (acquired) drug resistance and an alarming proportion of virologic failure among patients under treatment, unveiling suboptimal access to antiretroviral therapy (ARV), low ARV adherence and dissemination of drug resistant HIV strains in primary infections. Our results call for immediate actions of public authority to implement preventive measures, serological screening and, for HIV-seropositive subjects, clinical and treatment follow-up in order to control HIV infection and limit the spread of drug resistance strains in Brazilian prisons.     

我国一例典型艾滋病家庭的确认及其病毒env基因片段的序列分析

报道一例我国典型的ＨＩＶ感染家庭,其中对新生儿通过垂直传播感染的早期诊断为我国首例报道。父亲通过静脉吸毒感染ＨＩＶ,经性途径传播给妻子,并通过母婴途径传播至婴儿,导致婴儿发病。通过血清学、ＰＣＲ检测和病毒培养确认为整个家庭的感染。序列分析结果强烈支持杂来自同一毒株,流行背景主实了上述感染的传播途径。     

High Prevalence of HIV, HCV, HBV and Co-Infection and Associated Risk Factors among Injecting Drug Users in Yunnan Province, China

Objective

To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China.

Methods

2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections.

Results

The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection.

Conclusions

HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors.     

Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation

Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories.     

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.