Prevalence of hepatitis B and C virus co-infection in HIV positive patients attending a health institution in southeast Nigeria.

BACKGROUND: The health of people living with HIV/AIDS becomes progressively worse when co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), resulting in shortened life span. The modes of transmission of HIV, HBV and HCV are similar. OBJECTIVE: To determine the prevalence of HBV and HCV co-infection in HIV patients. METHOD: This was a retrospective study of serology test results for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) of HIV positive patients registered from 2008-2013 (6years) at the University of Nigeria Teaching Hospital. Adult patients with confirmed HIV seropositivity were included. Ethical approval was obtained and confidentiality of the patient information was maintained. Laboratory records were reviewed to obtain HBsAg, anti-HCV, and CD4 T-lymphocyte results. Prevalence was determined by the number of positive results over total number of patients tested. Chi-square test was used to determine relationships and p<0.05 was considered to be statistically significant. RESULTS: 4663 HIV patient records were included comprising 3024 (65%) females and 1639 (35%) males. Serology results showed 365/4663 (7.8%) tested HBsAg-positive only; 219/4663 (4.7%) tested anti-HCV-positive only; and 27/4663 (0.58%) tested both HBsAg and anti-HCV-positive. Correlation of age and sex were statistically significant with HBV and HCV (p<0.05) but not CD4 count (p>0.05). CONCLUSION: HBV co-infection was more prevalent than HCV, and triple infection was also observed. Screening for these viral infections in the HIV population is necessary for early identification to enable appropriate, holistic management of these patients.

Viral Hepatitis and Human Immunodeficiency Virus Testing and Linkage to Care for Individuals Enrolled in an Opioid Treatment Program.

BACKGROUND: In the United States, many opioid treatment programs (OTPs) do not offer viral hepatitis (VH) or human immunodeficiency virus (HIV) testing despite high prevalence among OTP clients. We initiated an opt-out VH and HIV testing and linkage-to-care program within our OTP. METHODS: All OTP intakes are screened for VH and HIV and evaluated for rescreening annually. A patient navigator reviews laboratory results and provides counseling in the OTP clinic. The medical record is queried to identify individuals with previously diagnosed, untreated VH or HIV. Navigation support is provided for linkage or relinkage to VH or HIV care. RESULTS: Between March 2018 and Februrary 2019, 532 individuals were screened for hepatitis C virus (HCV), 180 tested HCV antibody positive (34%), and 108 were HCV-ribonucleic acid (RNA) positive (20%). Sixty individuals were identified with previously diagnosed, untreated HCV. Of all HCV RNA+, 49% reported current injection drug use (82 of 168). Ninety-five individuals were seen by an HCV specialist (57% of HCV RNA+), 72 started treatment (43%), and 69 (41%) completed treatment. Individuals with primary care providers were most likely to start treatment. Four individuals were diagnosed with hepatitis B; 0 were diagnosed with HIV. CONCLUSIONS: The implementation of an OTP-based screening and navigation protocol has enabled significant gains in the identification and treatment of VH in this high prevalence setting.

Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor.

Cholesterol-PIE12-trimer (CPT31) is a potent d-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a simian-HIV chimeric virus AD8 (SHIVAD8) macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

Integrated HIV testing, prevention, and treatment intervention for key populations in India: a cluster-randomised trial.

BACKGROUND: To achieve reductions in HIV incidence, we need strategies to engage key population at risk for HIV in low-income and middle-income countries. We evaluated the effectiveness of integrated care centres in India that provided single-venue HIV testing, prevention, and treatment services for people who inject drugs (PWID) and men who have sex with men (MSM). METHODS: We did baseline respondent-driven sampling surveys in 27 sites across India, and selected 22 of these (12 PWID and ten MSM) for a cluster randomised trial on the basis of high HIV prevalence and logistical considerations. We used stratified (by PWID and MSM), restricted randomisation to allocate sites to either the integrated care intervention or usual care (11 sites per group). We implemented integrated care centres in 11 cities (six PWID integrated care centres embedded within opioid agonist treatment centres and five MSM centres within government-sponsored health services), with a single integrated care centre per city in all but one city. After a 2-year intervention phase, we did respondent-driven sampling evaluation surveys of target population members who were aged 18 years or older at all sites. The primary outcome was self-reported HIV testing in the previous 12 months (recent testing), determined via the evaluation survey. We used a biometric identification system to estimate integrated care centre exposure (visited an integrated care centre at least once) among evaluation survey participants at intervention sites. This trial is registered with ClinicalTrials.gov, number NCT01686750. FINDINGS: Between Oct 1, 2012, and Dec 19, 2013, we recruited 11 993 PWID and 9997 MSM in the baseline survey and, between Aug, 1 2016, and May 27, 2017, surveyed 11 721 PWID and 10 005 MSM in the evaluation survey using respondent-driven sampling, across the 22 trial sites. During the intervention phase, integrated care centres provided HIV testing for 14 698 unique clients (7630 PWID and 7068 MSM. In the primary population-level analysis, recent HIV testing was 31% higher at integrated care centres than at usual care sites (adjusted prevalence ratio [PR] 1·31, 95% CI 0·95-1·81, p=0·09). Among survey participants at intervention sites, integrated care centre exposure was lower than expected (median exposure 40% at PWID sites and 24% at MSM sites). In intervention sites, survey participants who visited an integrated care centre were more likely to report recent HIV testing than were participants who had not (adjusted PR 3·46, 2·94-4·06). INTERPRETATION: Although integrated care centres increased HIV testing among visitors, our low exposure findings suggest that the scale-up of a single integrated care centre in most cities was insufficient to serve the large PWID and MSM populations. Future work should address the use of population size estimates to guide the dose of combination HIV interventions targeting key populations. FUNDING: US National Institutes of Health and the Elton John AIDS Foundation.

Ethical issues associated with HIV phylogenetics in HIV transmission dynamics research: A review of the literature using the Emanuel Framework.

The reduced costs of DNA sequencing and the use of such data for HIV-1 clinical management and phylogenetic analysis have led to a massive increase of HIV-1 sequences in the last few years. Phylogenetic analysis has shed light on the origin, spread and characteristics of HIV-1 epidemics and outbreaks. Phylogenetic analysis is now also being used to advance our knowledge of the drivers of HIV-1 transmission in order to design effective interventions. However, HIV phylogenetic analysis presents unique ethical challenges, which have not been fully explored. This review presents an analysis of what appear to be key ethical issues in HIV phylogenetics in the hope of stimulating further conceptual and empirical work in this rapidly emerging area. We structure the review using the Emanuel Framework, a systematic, holistic framework, which has been adapted for use in developing countries, which bear the brunt of the HIV-1 pandemic.

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

Double G-quadruplexes in a copper nanoparticle based fluorescent probe for determination of HIV genes.

A DNA-templated copper nanoparticle (CuNP) probe has been developed for the determination of the human immunodeficiency virus oligonucleotide (HIV-DNA). The function of the probe relies on affinity binding-induced DNA hybridization associated with the use of double G-quadruplexes. Double-stranded DNA (dsDNA) with poly(AT-TA) bases was used as a template for synthesis of dsDNA-CuNPs. These have weak fluorescence. In the next step, two G-rich sequences that are linked to both sides of the ds-DNA are locked by HIV complementary DNA (cDNA). If HIV-DNA is introduced, it will hybridize with cDNA, thereby transforming the two G-rich sequences into G-quadruplexes. This enhances the fluorescence of the adjacent dsDNA-CuNPs. Fluorescence increases linearly in the 1 to 200 and 250-1000 nM HIV-DNA concentration range, and the detection limit is 13 pM. This enzyme-free fluorometric assay is time-saving, easily operated, and therefore has large potential in biosensing because it may be extended to various other DNA targets. Graphic abstract Double-strand DNA-templated copper nanoparticles (DNA-CuNPs) have weak fluorescence. When Human Immunodeficiency Virus oligonucleotide (HIV-DNA) is added, it completely hybridized with HIV complementary DNA (cDNA). As a result, the two exposed G-rich sequences are transformed into G-quadruplexes, and an apparent increase in the fluorescence intensity can be observed. (AA: ascorbic acid).

Limited Marginal Utility of Deep Sequencing for HIV Drug Resistance Testing in the Age of Integrase Inhibitors.

HIV drug resistance genotyping is a critical tool in the clinical management of HIV infections. Although resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect low-frequency alleles. However, the clinical value added from NGS approaches to antiviral resistance testing remains to be demonstrated. We compared the variant detection capacity of NGS versus Sanger sequencing methods for resistance genotyping in 144 drug resistance tests (105 protease-reverse transcriptase tests and 39 integrase tests) submitted to our clinical virology laboratory over a four-month period in 2016 for Sanger-based HIV drug resistance testing. NGS detected all true high-frequency drug resistance mutations (>20% frequency) found by Sanger sequencing, with greater accuracy in one instance of a Sanger-detected false positive. Freely available online NGS variant callers HyDRA and PASeq were superior to Sanger methods for interpretations of allele linkage and automated variant calling. NGS additionally detected low-frequency mutations (1 to 20% frequency) associated with higher levels of drug resistance in 30/105 (29%) protease-reverse transcriptase tests and 4/39 (10%) integrase tests. In clinical follow-up of 69 individuals for a median of 674 days, we did not find a difference in rates of virological failure between individuals with and without low-frequency mutations, although rates of virological failure were higher for individuals with drug-relevant low-frequency mutations. However, all 27 individuals who experienced virological failure reported poor adherence to their drug regimen during the preceding follow-up time, and all 19 who subsequently improved their adherence achieved viral suppression at later time points, consistent with a lack of clinical resistance. In conclusion, in a population with low antiviral resistance emergence, NGS methods detected numerous instances of minor alleles that did not result in subsequent bona fide virological failure due to antiviral resistance.

The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors.

Background: Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of human immunodeficiency virus (HIV)-infected individuals. Owing to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virologic failure while using DTG monotherapy. Methods: We evaluated the effect of the S230R substitution in regard to integrase enzyme activity, viral infectivity, replicative capacity, and susceptibility to different INSTIs by biochemical and cell-based assays. Results: The S230R substitution conferred a 63% reduction in enzyme efficiency. S230R virus was 1.29-fold less infectious than wild-type virus but could replicate in PM1 cells without significant delay. Resistance levels against DTG, cabotegravir, raltegravir, and elvitegravir in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively, in virus with the S230R substitution. Conclusions: Our data indicate that the S230R substitution is comparable to the previously reported R263K substitution in some respects. Virologic failure during DTG monotherapy can occur through the development of the S230R or R263K mutation, without the need for high-level DTG resistance.

Toward elimination of mother-to-child transmission of HIV in South Africa: how best to monitor early infant infections within the Prevention of Mother-to-Child Transmission Program.

BACKGROUND: South Africa has utilized three independent data sources to measure the impact of its program for the prevention of mother-to-child transmission (PMTCT) of HIV. These include the South African National Health Laboratory Service (NHLS), the District Health Information System (DHIS), and South African PMTCT Evaluation (SAPMTCTE) surveys. We compare the results of each, outlining advantages and limitations, and make recommendations for monitoring transmission rates as South Africa works toward achieving elimination of mother-to-child transmission (eMTCT). METHODS: HIV polymerase chain reaction (PCR) test data, collected between 1 January 2010 to 31 December 2014, from the NHLS, DHIS and SAPMTCTE surveys were used to compare early mother-to-child transmission (MTCT) rates in South Africa. Data from the NHLS and DHIS were also used to compare early infant diagnosis (EID) coverage. RESULTS: The age-adjusted NHLS early MTCT rates of 4.1% in 2010, 2.6% in 2011 and 2.3% in 2012 consistently fall within the 95% confidence interval as measured by three SAPMTCTE surveys in corresponding time periods. Although DHIS data over-estimated MTCT rates in 2010, the MTCT rate declines thereafter to converge with age-adjusted NHLS MTCT rates by 2012. National EID coverage from NHLS data increases from around 52% in 2010 to 87% in 2014. DHIS data over-estimates EID coverage, but this can be corrected by employing an alternative estimate of the HIV-exposed infant population. CONCLUSION: NHLS and DHIS, two routine data sources, provide very similar early MTCT rate estimates that fall within the SAPMTCTE survey confidence intervals for 2012. This analysis validates the usefulness of routine data sources to track eMTCT in South Africa.

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

INTRODUCTION: HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. METHODS: Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. RESULTS: Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. CONCLUSIONS: The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant.

Evidence of susceptibility to lamivudine-based HAART and genetic stability of hepatitis B virus (HBV) in HIV co-infected patients: A South African longitudinal HBV whole genome study.

BACKGROUND: Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa. MATERIALS AND METHODS: This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined. The HBV genome was amplified from longitudinal samples and characterized by Bayesian inference, mutational analysis, and identification of immune selection pressure. RESULTS: All patients exhibited persistent chronic HBV infection at baseline, as well as over the course of follow-up despite exposure to 3TC-based HAART. The polymerase gene in all isolates was relatively variable prior to HAART initiation at baseline and during the course of follow-up, although primary drug resistance mutations were not detected. All but one patient were infected with HBV subgenotype A1. The divergence rates between baseline and the last follow-up sequences ranged from 0 to 2.0×10(-3) substitutions per site per year (s/s/y). Positive selection pressure was evident within the surface and core genes. CONCLUSION: Despite persistent HBV infection in the HIV co-infected patients exposed to long term 3TC-based HAART, the molecular evolution of HBV over a 5year period was unremarkable. In addition, HBV exhibited minimal genetic variability overtime.

A zwitterionic 1D/2D polymer co-crystal and its polymorphic sub-components: a highly selective sensing platform for HIV ds-DNA sequences.

Polymorphic compounds {[Cu(dcbb)2(H2O)2]·10H2O}n (2, 1D chain), [Cu(dcbb)2]n (3, 2D layer) and their co-crystal {[Cu(dcbb)2(H2O)][Cu(dcbb)2]2}n (4) have been prepared from the coordination reaction of a 2D polymer [Na(dcbb)(H2O)]n (1, H2dcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide) with Cu(NO3)2·3H2O at different temperatures in water. Compounds 2-4 have an identical metal-to-ligand stoichiometric ratio of 1 : 2, but absolutely differ in structure. Compound 3 features a 2D layer structure with aromatic rings, positively charged pyridinium and free carboxylates on its surface, promoting electrostatic, π-stacking and/or hydrogen-bonding interactions with the carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, delineates as P-DNA). The resultant P-DNA@3 system facilitated fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@3 system functions as an efficient fluorescent sensor selective for HIV double-stranded DNA (HIV ds-DNA) due to the formation of a rigid triplex structure with the recovery of FAM fluorescence. The system reported herein also distinguishes complementary HIV ds-DNA from mismatched target DNA sequences with the detection limit of 1.42 nM.

Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing.

In a South African cohort of participants living with HIV developing virological failure on first-line tenofovir disoproxyl fumarate (TDF)-based regimens, at least 70% of participants demonstrated TDF resistance according to combined Sanger and MiSeq genotyping. Sanger sequencing missed the K65R mutation in 30% of samples. Unless HIV genotyping is available to closely monitor epidemiological HIV resistance to TDF, its efficacy as second-line therapy will be greatly compromised.

Cost-effectiveness of genotype testing for primary resistance in Brazil.

OBJECTIVE: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. DESIGN: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). METHODS: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12,300. RESULTS: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to $44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. CONCLUSIONS: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

Insight into HIV of IFN-induced myxovirus resistance 2 (MX2) expressed by traditional Chinese medicine.

Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had been published in 2013. In this report, the expression of the IFN-induced myxovirus resistance 2 (MX2) had been defined the function to kill the human immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine (TCM) database by simulating molecular docking and molecular dynamics could select candidate compounds, which may express MX2 against HIV. Saussureamine C, Crotalaburnine, and Precatorine are selected based on the highest docking score and other TCM compounds. The data from molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond with structure variations, this research could assess the interaction between protein and ligand interaction. In addition to the detection of TCM compound efficacy, we suggest that Saussureamine C is better than the others in protein-ligand interaction and the structural variation to express MX2.

Screening for noise in gene expression identifies drug synergies.

Stochastic fluctuations are inherent to gene expression and can drive cell-fate specification. We used such fluctuations to modulate reactivation of HIV from latency-a quiescent state that is a major barrier to an HIV cure. By screening a diverse library of bioactive small molecules, we identified more than 80 compounds that modulated HIV gene-expression fluctuations (i.e., "noise"), without changing mean expression. These noise-modulating compounds would be neglected in conventional screens, and yet, they synergized with conventional transcriptional activators. Noise enhancers reactivated latent cells significantly better than existing best-in-class reactivation drug combinations (and with reduced off-target cytotoxicity), whereas noise suppressors stabilized latency. Noise-modulating chemicals may provide novel probes for the physiological consequences of noise and an unexplored axis for drug discovery, allowing enhanced control over diverse cell-fate decisions.