hiv resistance

Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential...

OBJECTIVES: The objectives of this study were to determine HIV drug resistance prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) regimens affect drug resistance. DESIGN: Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT treatment regimens...

OBJECTIVE: Long-acting rilpivirine is a candidate for pre-exposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (RT-E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing Human Leukocyte Antigen (HLA)-B*18 where RT-E138X arises as an immune escape mutation. We investigate the global prevalence, B*18-linkage and replicative cost of RT-E138X and its regional implications for rilpivirine PrEP...

BACKGROUND: Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. OBJECTIVE: To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. METHODS: This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months...

Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches...

Objective: To understand the characteristic of subtype distribution among foreigners who were living with HIV-1, in Guangzhou. Methods: HIV-1 RNAs were extracted from 114 serum specimens in foreigners diagnosed with HIV-1 infections between 2008 and 2010, and in 2015. Partial pol gene of HIV-1 genome from these RNA samples were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) with nucleotide sequenced. Subsequently, phylogenetic tree was reconstructed using the pol sequences of samples and references...

Viral infections are a major burden to human and animal health. Immune response against viruses consists of innate and adaptive immunity which are both critical for the eradication of the viral infection. The innate immune system is the first line of defense against viral infections. Proper innate immune response is required for the activation of adaptive, humoral and cell-mediated immunity. Macrophages are innate immune cells which have a central role in detecting viral infections including influenza A and human immunodeficiency viruses...

HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...

Background: Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. Methods: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months...

HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...

In this paper, I examine disputes over recent claims that male circumcision reduces HIV risk to suggest a complicated relationship between risk individualization and categorization. Whereas randomized controlled trials (RCTs) conducted in sub-Saharan Africa appear to have provided key evidence for the World Health Organization's endorsement of male circumcision as an HIV prevention strategy, RCTs alone did not provide evidence for the underlying causal mechanism. For that, medical authorities have turned to histo-immunological studies of the foreskin's biomolecular vulnerability to HIV, thus molecularizing risk...

Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...

Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...

Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance...

Cryptococcosis in HIV-seronegative patients is rarely reported from India. This prospective study was conducted to look for cryptococcal meningitis in HIV-seronegative individuals and compare their laboratory features to cryptococcal meningitis in HIV-seropositive patients. Cerebrospinal fluid was collected from 153 suspected cases of meningitis and subjected to India ink preparation, antigen detection, and culture. Nineteen samples tested positive for Cryptococcus neoformans infection. Seventeen and two patients were HIV reactive and nonreactive, respectively...

Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms...

One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection...

BACKGROUND: The World Health Organization defines HIV virologic failure as two consecutive viral loads >1,000 copies/mL, measured 3-6 months apart with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort. SETTING: The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation, and monitored adherence with electronic pill bottles...

We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31 and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31 and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers...

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells...