A Cross-Sectional Survey of HIV Testing and Prevalence in Twelve Brazilian Correctional Facilities

BackgroundPrior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons.MethodsWe administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy.ResultsWe recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18–1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20–1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43–1.98), history of mental illness (AOR 1.52; 95% CI: 1.31–1.78) and previous surgery (AOR 1.31; 95% CI: 1.12–1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73–22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13–4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64–6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20–5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care.ConclusionsHIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.     

Assessing the HIV-1 Epidemic in Brazilian Drug Users: A Molecular Epidemiology Approach

Person who inject illicit substances have an important role in HIV-1 blood and sexual transmission and together with person who uses heavy non-injecting drugs may have less than optimal adherence to anti-retroviral treatment and eventually could transmit resistant HIV variants. Unfortunately, molecular biology data on such key population remain fragmentary in most low and middle-income countries. The aim of the present study was to assess HIV infection rates, evaluate HIV-1 genetic diversity, drug resistance, and to identify HIV transmission clusters in heavy drug users (DUs). For this purpose, DUs were recruited in the context of a Respondent-Driven Sampling (RDS) study in different Brazilian cities during 2009. Overall, 2,812 individuals were tested for HIV, and 168 (6%) of them were positive, of which 19 (11.3%) were classified as recent seroconverters, corresponding to an estimated incidence rate of 1.58%/year (95% CI 0.92–2.43%). Neighbor joining phylogenetic trees from env and pol regions and bootscan analyses were employed to subtype the virus from132 HIV-1-infected individuals. HIV-1 subtype B was prevalent in most of the cities under analysis, followed by BF recombinants (9%-35%). HIV-1 subtype C was the most prevalent in Curitiba (46%) and Itajaí (86%) and was also detected in Brasília (9%) and Campo Grande (20%). Pure HIV-1F infections were detected in Rio de Janeiro (9%), Recife (6%), Salvador (6%) and Brasília (9%). Clusters of HIV transmission were assessed by Maximum likelihood analyses and were cross-compared with the RDS network structure. Drug resistance mutations were verified in 12.2% of DUs. Our findings reinforce the importance of the permanent HIV-1 surveillance in distinct Brazilian cities due to viral resistance and increasing subtype heterogeneity all over Brazil, with relevant implications in terms of treatment monitoring, prophylaxis and vaccine development.     

Drug injection and HIV prevalence in inmates of Glenochil prison.

OBJECTIVE--To determine prevalence of HIV infection and drug injecting behaviour among inmates of Glenochil Prison on a specified date a year after an outbreak of hepatitis B and HIV infection. DESIGN--Cross sectional: voluntary, anonymous HIV salivary antibody surveillance and linked self completion questionnaire on risk factors. SETTING--Glenochil prison, Scotland, a year after an outbreak of hepatitis B and HIV transmission related to drug injection. SUBJECTS--352 prisoners, of whom 295 (84%) took part; 284 questionnaires (96%) passed logical checks. MAIN OUTCOME MEASURES--HIV prevalence; proportion of all inmates who had ever injected drugs, had ever injected inside prison, had started injecting drugs while inside prison. RESULTS--More than half (150/284) the current inmates were also in Glenochil Prison during the critical period of January to June 1993, when hepatitis B and HIV were transmitted. Similar proportions of current inmates and men who were also in Glenochil during the critical period were drug users (27% (75/278) v 30% (44/149)). A quarter of injecting drug users (18/72) had first injected inside prison, irrespective of whether they were in Glenochil in January to June 1993 and regardless of the calendar period when they first injected. Significantly more inmates from Glasgow (41%; 56/138) than from Edinburgh (21%; 7/34) or elsewhere (11%; 12/106) were injecting drug users. On testing for HIV, seven saliva samples out of 293 gave positive results--four were presumed to be from inmates known to be infected with HIV, and the others from injecting drug users from Glasgow, all of whom had been in Glenochil during January to June 1993, when two of the three had injected drugs and had been tested for HIV, with negative results. The ratio of overall (2.4%) to disclosed (1.4%) HIV prevalence was 1.7. For men who had injected drugs in Glenochil during January to June 1993, HIV prevalence was estimated at 29%. CONCLUSION--Between a quarter and a third of prisoners who injected drugs in Glenochil in January to June 1993 were infected with HIV. There is widespread ongoing risk of bloodborne virus infection within prisons, which is probably long standing but demands urgent attention.     

Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

BackgroundRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.ConclusionsMost TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.     

Molecular Epidemiology and Transmission Dynamics of Recent and Long-Term HIV-1 Infections in Rural Western Kenya

Objective

To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya.

Methods

Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression.

Results

Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2–4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002.

Conclusions

Recent HIV-1 infection was more frequent among 13–19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.     

Evolutionary History of HIV-1 Subtype B and CRF01_AE Transmission Clusters among Men Who Have Sex with Men (MSM) in Kuala Lumpur,Malaysia

HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.     

Molecular epidemiological analysis of the spread of human immunodeficiency virus (HIV) infection in the Novosibirsk region

The dynamics of the spread of individual subtypes of type 1 HIV (HIV-1), circulating in the Novosibirsk region during the epidemic rise of HIV infection was under study. The epidemic of HIV-1 in Novosibirsk has a pattern similar to that in Russia as a whole. At the initial stage of epidemics multiple sources of virus determine the heterogeneity of the isolated subtypes of HIV-1. Then the parenteral route of HIV transmission, connected with the intravenous use of narcotic drugs, becomes dominant. Recently the spread of HIV-1 from the group of intravenous drug users to other groups of the population has been observed. In the circulation of HIV-1 among drug users the leading role was shown to belong to subtype A, which ensures its rapid spread and dominating role in the epidemic process. Further spread of the HIV-1 epidemic is expected to proceed in parallel to the spread of viral hepatitis, sexually transmitted diseases and drug addiction. Thus, HIV-1, subtype A, may be assumed to be dominant in the Novosibirsk region in the nearest future.     

HIV Transmission in a State Prison System, 1988–2005

Introduction

HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988–2005 among male Georgia prison inmates.

Methods

We analyzed medical and administrative data to describe seroconverters'' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters'' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks.

Results

Forty-one (47%) seroconverters were diagnosed with HIV from July 2003–June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0–0.10) and tattooing (OR = 0.03, 95% CI: <0.01–0.20) in prison after their HIV diagnosis than before. Of 67 seroconverters'' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant.

Discussion

Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates.     

Care of HIV-infected patients in China

Compared with high infection areas of the world, the total HIV infection rate in China is relatively low. Nonetheless, because of China's vast territory and large population, the potential infection risk must be taken seriously. In the next few years, needle sharing among injection drug users will remain the most common route of transmission for the HIV/AIDS epidemic in China. Unprotected sex is gradually becoming a major route of transmission. China began to implement HAART in 1999 according to international standards. Prior to 2003, there were only about 150 HIV/AIDS patients were treated with HAART in some clinical trials and about 100 HIV/AIDS patients were treated by private sources. Results of those treatments are the scientific basis for development of the therapeutic strategies in China. In March of 2003, the Chinese government initiated China CARES program. In November of 2003, the Chinese Ministry of Health announced a national policy of free ARV treatment to all HIV+ Chinese citizens who were in poverty and required ARV therapy. There are total of 19,456 HIV/AIDS patients received free ARV drugs to date in 159 regions and 441 towns. Current challenges are how to follow-up and evaluate those patients in the clinical settings. The longer the therapy is postponed, the more side effects and the higher probability of drug resistance are going to occur. It remains unclear, therefore, when HAART regimen should be started in the HIV/AIDS population in China.     

Parental LTRs are important in a construct of a stable and efficient replication-competent infectious molecular clone of HIV-1 CRF08_BC

Circulating recombinant forms (CRFs) of HIV-1 have been identified in southern China in recent years. CRF08_BC is one of the most predominant subtypes circulating in China. In order to study HIV subtype biology and to provide a tool for biotechnological applications, the first full-length replication-competent infectious molecular clone harboring CRF08_BC is reported. The construction of this clone pBRGX indicates that a moderate-copy number vector is required for its amplification in E. coli. In addition, it is shown that the parental CRF08_BC LTRs are important for generating this efficient replication-competent infectious clone. These observations may aid in the construction of infectious clones from other subtypes. Both the pBRGX-derived virus and its parental isolate contain CCR5 tropism. Their full-length genomes were also sequenced, analyzed, compared and deposited in GenBank (JF719819 and JF719818, respectively). The availability of pBRGX as the first replication-competent molecular clone of CRF08_BC provides a useful tool for a wide range of studies of this newly emergent HIV subtype, including the development of HIV vaccine candidates, antiviral drug screening and drug resistance analysis.     

Molecular investigation into outbreak of HIV in a Scottish prison.

OBJECTIVES: To support already established epidemiological links between inmates of Glenochil prison positive for HIV infection by using molecular techniques and thus provide evidence of the extent of acquisition during a recent outbreak of the disease resulting from needle sharing. To identify possible sources of the outbreak, and to demonstrate the ability of the methodology to make further links beyond the original outbreak. DESIGN: Viral sequences obtained from the blood of HIV positive prisoners previously identified by standard epidemiological methods were compared with each other and with sequences from other Scottish patients. SETTING: Glenochil prison for men, central Scotland. SUBJECTS: Adult inmates and their possible contacts. RESULTS: Phylogenetic analysis of viral sequences in two different genomic regions showed that 13 of the 14 HIV positive prisoners had been infected from a common source. Previous research had shown that six of these had acquired their infection in Glenochil; molecular evidence suggests that more than double this number were infected while incarcerated. Virus from two long term HIV positive patients who were in the prison at the time of the outbreak but who were not identified in the original or subsequent surveys was sufficiently different to make it unlikely that they were the source. A viral sequence from heterosexual transmission from one inmate showed the ability of these techniques to follow the infection through different routes of infection. CONCLUSION: The number of prisoners infected with HIV during the 1993 outbreak within Glenochil prison was more than twice that previously shown. This shows the potential for the spread of bloodborne diseases within prisons by injecting drugs.     

Voluntary anonymous linked study of the prevalence of HIV infection and hepatitis C among inmates in a Canadian federal penitentiary for women.

OBJECTIVE: To determine the seroprevalence of HIV infection and hepatitis C among inmates of a federal penitentiary for women. DESIGN: Voluntary, anonymous, linked, point-prevalence study involving testing of blood samples for antibodies to HIV and hepatitis C virus. PARTICIPANTS: All inmates of the multilevel security federal Prison for Women, Kingston, Ont., who volunteered to participate in the study. Inmates at this long-stay facility are from across Canada. OUTCOME MEASURE: Seroprevalence rate among participants of antibodies to HIV and hepatitis C virus. RESULTS: Of the 130 inmates available for study 113 (86.9%) agreed to donate a blood sample. One woman (0.9%) was HIV positive; 45 (39.8%) were positive for hepatitis C antibody. CONCLUSIONS: It is possible to obtain a high participation rate in a voluntary, anonymous, linked point-prevalence study in a long-stay penitentiary. The HIV seroprevalence rate of 0.9% is lower than that found in studies in provincial (short-stay) prisons. However, the high rate of antibodies to hepatitis C suggests a significant level of risk behaviour, most likely injection drug use, and suggests the potential for a rapid increase in the rate of HIV infection should the number of newly admitted HIV-positive inmates who use injection drugs rise.     

海南省及云南西双版纳州HIV-1的分子流行病学比较研究

目的调查比较HIV-1在海南省及云南西双版纳州的流行情况及分子流行病学分析高危因素传播的情况以及传播链的鉴定。方法我们与海南省CDC及西双版纳州CDC合作在其境内开展了HIV血清学调查,筛查了海南省（1991～2006）及西双版纳州（1996～2005）高危人群志愿者血清样本。在本次两地调查中,我们通过系统进化分析方法,对已诊断的HIV感染者进行分子流行病学的追踪,来分析其中的主要流行亚群以及结合个案追踪进行传播链的鉴定。结果我们共筛查了海南省499725人,共检出HIV阳性感染者523例（0.1%）,以注射器吸毒感染为主要传播途径（经共用注射器吸毒感染占69．2％、经性接触传播占19．3％、供血和使用血液／血液制品感染占3．3％、母婴传播占0．8％、不详占7．7％）。然而,在西双版纳州筛查中发现了较海南省高20倍的检出率：在25390受检人中,共检出HIV阳性感染者501例（2％）并以异性性传播为主（经异性性接触传播占77．3％、经共用注射器吸毒感染占21．1％、经同性性接触传播占0．4％、母婴传播占1．2％）。在海南省抽样的83人中,以CRF01_-AE重组亚型（70人,84．3％）为主要病毒亚型,其他病毒亚型包括B’亚型（8人）、C亚型（2人）、CRF08_BC重组亚型（1人）、B亚型（1人）和1个未报道过的CRF01～AE／B’重组亚型。同样,在版纳抽样的44人中,也以CRF01_AE重组亚型（27人,61．3％）为主要病毒亚型,其他病毒亚型包括CRF08_BC重组亚型（15人）、G亚型（1人）、和1个未报道过的B／C重组亚型。在海南省抽样中有66人（79．5％）分布于4个大小不同的传播群,传播群1（59人）较大（奠基效应）,属于CRF01_AE重组亚型,传播群2、3、4则较小,分别为3、2、2人,分别属于CRF01_AE重组亚型、C亚型和B’亚型。相反,在版纳抽样中有18人（40．9％）分布于8个较小的传播群（每群平均含2．25感染个体）。在海南省抽样中怀疑的6对异性性接触的传播链中,经系统进化分析方法确认了其中的4对,2对被拒绝。在版纳抽样中怀疑的8对异性性接触的传播链中,经系统进化分析方法确认了其中的5对,2对被拒绝,1对无法分析,此外还新发现了3对异性性接触传播群。结论HIV-1感染者的分子流行病学的追踪和分析对于追溯艾滋病流行的源头和地区性预防策略的制定有着重大的意义。     

Human immunodeficiency virus seroprevalence among inmates of the penitentiary complex of the region of campinas, state of S?o Paulo, Brazil.

Six hundred and ninety three male inmates from three penitentiaries, two (A and B) maximum-security systems and one (C) minimum-security facility, located in Campinas, State of S?o Paulo, Brazil were studied for the presence of human immunodeficiency virus (HIV) antibodies, using a cross-sectional design. The search for anti-HIV antibodies in 693 samples of sera collected was carried out by two serological tests: (a) the Microparticle enzyme immunoassay-HIV-1 and HIV-2 (MEIA) (Abbott Laboratories) and (b) the Western Blot-HIV-1 (WB) (Cambridge Biotech Corporation) to confirm positive results with MEIA. Sera reactivity for HIV antibodies was 14.4%. The highest frequency of anti-HIV antibodies was found in the A and B maximum-security prisons: 17% and 21.5%, respectively. In prison C, the frequency of reagents was 10.9%. Seventy three inmates, initially negative in the MEIA test, were checked again five and seven months later. Three of them, all from the maximum-security facilities, became reactive in the MEIA test, with confirmation in the WB, suggesting that serological conversion had occurred after imprisonment.     

Outbreak of HIV infection in a Scottish prison.

OBJECTIVE--To investigate the possible spread of HIV infection and its route of transmission among prison inmates. DESIGN--In response to an outbreak of acute clinical hepatitis B and two seroconversions to HIV infection, counselling and testing for HIV were offered to all inmates over a two week period in July 1993. Information was sought about drug injecting, sexual behaviour, and previous HIV testing. SETTING--HM Prison Glenochil in Scotland. SUBJECTS--Adult male prisoners. MAIN OUTCOME MEASURES--Uptake of HIV counselling and testing; occurrence and mode of HIV transmission within the prison. RESULTS--Of a total 378 inmates, 227 (60%) were counselled and 162 (43%) tested for HIV. Twelve (7%) of those tested were positive for antibody to HIV. One third (76) of those counselled had injected drugs at some time, of whom 33 (43%) had injected in Glenochil; all 12 seropositive men belonged to this latter group. Thirty two of these 33 had shared needles and syringes in the prison. A further two inmates who injected in the prison were diagnosed as positive for HIV two months previously. Evidence based on sequential results and time of entry into prison indicated that eight transmissions definitely occurred within prison in the first half of 1993. CONCLUSION--This is the first report of an outbreak of HIV infection occurring within a prison. Restricted access to injecting equipment resulted in random sharing and placed injectors at high risk of becoming infected with HIV. Measures to prevent further spread of infection among prison injectors are urgently required.     

南宁市HIV-1/AIDS人群治疗前pol区遗传特性及蛋白结构分析

为探讨南宁市某县艾滋病病毒1型(HIV-1)感染人群中治疗前pol区遗传特性及蛋白结构变化情况,本研究通过RT-PCR扩增pol区部分序列并进行测序,将序列同源比对构建系统进化树;分型确定毒株亚型和斯坦福大学HIV耐药性数据库比对,分析耐药相关位点;SWISS-MODEL蛋白质同源数据库进行建模分析氨基酸的突变对蛋白质结构和功能的影响。本研究在90份HIV-1标本中获得46个pol区有效序列,共发现4种亚型,其中CRF01_AE占76.08%(35/46)、CRF08_BC占15.22%(7/46)、CRF07_BC占(3/46)6.52%、CRF59_01B1占2.17%(1/46);46个序列中有4例(8.69%)出现耐药突变位点,没有针对核苷酸反转录酶抑制剂(NRTI)的耐药突变;针对蛋白酶类抑制剂(PIs)1例,PR蛋白酶的柔性部位I47V位点发生突变,β折叠结构的I84V位点发生突变,都是异亮氨酸突变为缬氨酸;针对非核苷酸反转录酶抑制剂(NNRTI)有3例,2例位于活性中心的Y181C位点由酪氨酸突变为半胱氨酸,1例位于转角处的E138G位点由谷氨酸突变为甘氨酸。研究表明,南宁市某县HIV-1病毒CRF01_AE重组亚型比例最大,未经抗病毒治疗HIV1感染者中已经出现pol区耐药突变株,突变位点主要位于活性中心及柔性部位,传播水平已经处于中等流行状态。深入分析蛋白质与抑制剂相互作用机制,有助于为艾滋病抗病毒及耐药性监测方案提供科学依据。     

Molecular dynamics simulations applied to the study of subtypes of HIV-1 protease common to Brazil, Africa, and Asia

Africa accounts for the majority of HIV-1 infections worldwide caused mainly by the A and C viral subtypes rather than B subtype, which prevails in the United States and Western Europe. In Brazil, B subtype is the major subtype, but F, C, and A also circulate. These non-B subtypes present polymorphisms, and some of them occur at sites that have been associated with drug resistance, including the HIV-1 protease (PR), one important drug target. Here, we report a Molecular Dynamics study of the B and non-B PR complexed with the inhibitor ritonavir to delineate the behavior of each subtype. We compare root mean squared deviation, binding free energy by linear interaction energy approach, hydrogen bonds, and intermolecular contact surface area between inhibitor and PR. From our results, we can provide a basis to understand the molecular mechanism of drug resistance in non-B subtypes. In this sense, we found a decrease of approx 4 kcal/mol in ΔG of binding between B and non-B subtypes. This corresponds to the loss of one hydrogen bond, which is in agreement with our H-bond analysis. Previous experimental affinity studies reported analogous results with inhibition constant values for non-B PR.     

HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission

HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83). Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child) significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642). However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children’s DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV.