If a patient is suspected to have an HIV infection buy discount eriacta 100mg line erectile dysfunction in diabetes mellitus pdf, the result of viral load measurement can be used for confirmation (see chapter 6 100 mg eriacta for sale impotence questions. In this case order eriacta no prescription erectile dysfunction san antonio, a second serological test is not necessary. HIV PCR In addition to the serological test systems, molecular methods for detection of HIV RNA (nucleic acid amplifications tests, NAT) are available. PCR is the NAT most frequently used for HIV RNA detection. The quantitative detection of HIV RNA (a viral load determination) is one of the essential components of the monitoring of HIV infection (Wittek 2007, Thompson 2010). To increase the safety of blood products the HIV PCR is obliga- tory in the context of blood donation. Other indications for the use of the PCR are the exclusion of an HIV infection of newborns of HIV+ mothers (see below), the clarification of equivocal serological constellations or a suspected acute infection. According to new recommendations, PCR analysis may be used for confirmation of a reactive screening test result instead of a Western Blot. For this purpose, a PCR test is considered positive in case of a viral load above 1000 copies/ml. If the viral load amounts to less than 1000 copies/ml or the PCR is negative subsequent Western Blot analysis is obligatory (DVV/GfV 2015). However, the HIV PCR is not recommended as a screening test. Since false negative results are possible it cannot replace the serological screening test. Possible reasons for false negative results are as follows: 1. Commercially available HIV PCR tests usually do not cover HIV-2 (rare in Europe). HIV is characterized by a high degree of genetic diversity. In case of infection with a new or previously unknown variant sensitivity of the PCR may decrease due to mutations affecting the primer or probe binding sites. Through a so-called “dual target” PCR the risk of false negative test results due to sequence variability may be reduced (Chudy 2012; see also chapter 6. The “dual target” PCR is obligatory for screening blood donations. A small number of HIV+ patients can suppress viral replication in the absence of ART (“elite controllers”, prevalence less than 1%). Thus, despite serologically proven HIV infection a PCR test may be negative in those patients. The aim of the antiretroviral treatment is the reduction of the viral load below the detection limit. As a consequence, the use of a PCR as a HIV screening test in a successfully treated patient would lead to a false-negative testing result. Rapid tests Rapid HIV tests functionally correspond to a screening test, i. Rapid tests can be carried out quickly, easily and without any equipment expense and can therefore be used as so-called “point of care” tests. In addition to plasma and serum, full or capillary blood (from the fin- gertip or the ear lobe) is suitable as test material, so that no centrifuge is required. In some test systems urine or oral transudate (not saliva) may be used. However, rapid tests exhibit less sensitivity if specimens others than serum or plasma are used (Pavie 2010). Most frequently, rapid tests are based on immuno-chromatographic methods. Other techniques such as particle agglutination and immunofiltration are also used (Branson 2003, Greenwald 2006). Rapid tests produced according to the European directive 98/79/EC on in vitro diag- nostic medical devices (CE marking) are considered safe. These tests exhibit a high sensitivity and specificity in studies (Huppert 2010). However, apparently there are limitations regarding diagnosis of primary HIV infection: almost all currently avail- able rapid tests only detect HIV antibodies but not p24 antigen, corresponding to the (outdated) 3rd generation HIV test. Since 2009 a certified 4th generation rapid test (Determine HIV-1/2 Ag/Ab Combo, Inverness Medical) is available which not only detects but can also differentiate HIV antibodies and p24 antigen. Although the supe- riority of this rapid test compared to the 3rd generation rapid test was illustrated (Chetty 2012), some studies indicate a lack of sensitivity in the context of acute HIV infections (Kilembe 2012, Brauer 2013). In a comparative study the test exhibited deficiencies regarding the recognition of primary HIV infections. About one third of the samples of patients with acute HIV infection tested falsely negative. Reactivity was delayed by one week compared to a reference test (Mohrmann 2009). Rapid tests should be used only for initial orientation. The results of the testing should be con- firmed at the earliest opportunity in a routine laboratory with a standard HIV test. Rapid tests are particularly suitable for use in emergency situations where the test result has immediate consequences. These include emergency operations and needle- stick injuries. Also in pregnant women with unknown HIV status at delivery a rapid test can be useful. However, the cooperating laboratory should be contacted to indi- cate the need for a rapid HIV result. When necessary, the result of a conventional HIV test can be available within one hour upon receipt of the sample. Rapid tests are also useful in countries with poor medical infrastructure (UNAIDS/WHO 2009) and in the context of low-threshold testing for individuals who would otherwise not be tested. The diagnostic window The “diagnostic gap” or “window” indicates the time period between transmission of a pathogen and the onset of biochemical measurable infection markers such as antibodies, antigen or nucleic acids (Busch 1997). At the earliest, HIV antibody pro- duction begins two weeks after transmission. HIV-specific antibodies can be detected after four weeks in 60–65%, after six weeks in 80%, after eight weeks in 90% and after twelve weeks in 95% of cases. A “seronegative” chronic HIV infection is an absolute rarity and irrelevant in practice (Spivak 2010). The p24 antigen is detectable HIV Testing 19 about five days before seroconversion (the first occurrence of specific antibodies). Therefore, 4th generation diagnostic tests can shorten the diagnostic gap by simul- taneous detection of p24 antigen.
All consisted of placebo comparisons: five used sertraline cheap 100mg eriacta fast delivery erectile dysfunction normal age, five fluvoxamine purchase eriacta toronto impotence age 45, three compared fluoxetine eriacta 100mg erectile dysfunction 60, three paroxetine and one used citalopram. Overall, the drugs evaluated provided greater efficacy than placebo, however, there were differences in the incidence of adverse events, in particular nausea. Three - citalopram, fluvoxamine and paroxetine - had a greater rate of nausea compared to placebo; two - fluoxetine and sertraline - did not. Citalopram compared with placebo A fair multicenter study conducted in Europe and South Africa compared various fixed-doses of citalopram to placebo in 401 outpatients with OCD characterized as stable for more than 6 177 months. Loss to follow-up was 16 percent, with small differences between groups. All three doses of citalopram produced significantly more responders (≥ 25% improvement in Y-BOCS) than placebo (P<0. The high-dose citalopram (60 mg) response reached statistical significance at week 3, whereas the lower doses (20 mg and 40 mg) reached statistical significance at week 7. On the patient-rated Sheehan Disability Scale, the citalopram-treated patients showed significant improvements for most items. Adverse events were reported in 71 percent of subjects in the active treatment groups. The number of adverse events reported by persons on different citalopram doses did not differ significantly. Ejaculation failure was significantly different from placebo only in the 40 mg citalopram group. Summary of the evidence Three fair head-to-head studies provide evidence that there is no difference in efficacy between fluoxetine and sertraline or venlafaxine and paroxetine or escitalopram and paroxetine. Other evidence is insufficient to draw conclusions about comparative efficacy between one second- generation antidepressant and another. Effectiveness We did not identify any study with a high degree of generalizability. Efficacy 173, 174, #2557 169, 170: #3187, 171 Three head-to-head trials and four meta-analyses provide fair evidence that no difference in efficacy among evaluated second-generation antidepressants exists. Two head-to-head trials provide fair evidence that the efficacy of venlafaxine XR and paroxetine does 174, 175, 189 not differ in improving health outcomes; in a follow-up study, 42 percent of 167 nonresponders who switched to the alternative treatment achieved a response. One fair placebo-controlled study showed a significantly greater improvement in disability for citalopram Second-generation antidepressants 58 of 190 Final Update 5 Report Drug Effectiveness Review Project 177 compared to placebo. In a second study, citalopram-treated patients augmented with mirtazapine had a faster response than patients treated with citalopram alone, although 168 differences did not persist past 6 weeks. One study provides fair evidence that sertraline has a faster onset of action than 173 fluoxetine in the treatment of OCD. Another fair-rated study reported a faster response for 174 venlafaxine XR compared to paroxetine. A fair-rated study showed no difference between 175 escitalopram and paroxetine throughout 24 weeks of treatment. FDA-approved evidence exists for the general efficacy of fluoxetine, sertraline, paroxetine, and fluvoxamine for treating OCD. Evidence is insufficient about the efficacy of mirtazapine, bupropion, and nefazodone for treating OCD. Additionally, one study provides fair 177 evidence supporting a greater efficacy of citalopram than placebo. Interventions, numbers of patients, and quality ratings of studies in adults with obsessive-compulsive disorder Quality Author, Year Interventions N Results rating SSRIs compared with Placebo 170 No differences among Fair Ackerman et al. Panic Disorder Only fluoxetine, paroxetine, sertraline, and venlafaxine are currently approved by the FDA for the treatment of panic disorder. We viewed FDA approval as evidence for general efficacy and did not review placebo-controlled trials of fluoxetine, paroxetine, sertraline, and venlafaxine. For panic disorder, we identified four head-to-head trials of fair quality comparing one 190-194 SSRI, or other second-generation antidepressant to another. We excluded one study – a 191 single-blinded RCT with a poor quality rating for internal validity – from our findings, but we discuss it here briefly because of the minimal amount of published research on this topic. Second-generation antidepressants 59 of 190 Final Update 5 Report Drug Effectiveness Review Project Furthermore, we identified three placebo-controlled trials assessing the efficacy and tolerability 195-197 of fluvoxamine. Inclusion was generally determined by a criteria-based (DSM-III-R, DSM-IV) diagnosis of panic disorder in addition to a predefined frequency of weekly panic attacks. Patients with at least one to four panic attacks per week or eight in total over the past 4 weeks were eligible for inclusion. Both patients with and without agoraphobia were included in these trials. Common exclusion criteria were additional Axis I disorders, high suicidal risk, a history of alcohol or drug dependence or abuse, use of other psychotropic medications, and progressive medical disease. The primary outcome measure in all trials was the frequency of panic attacks as assessed with various scales (e. Secondary outcome measures included changes from baseline in the Panic Disorder Severity Score (PDSS), quality of life and health-related functional capacity (Sheehan Disability Scale [SDS], Fear Questionnaire [FQ]), the Phobia Scale, anxiety-related subscales of the MADRS and HAM-D, and global assessment methods (e. SSRIs compared to SSRIs in adult outpatients with Panic Disorder Four fair double-blinded RCTs compared the efficacy and tolerability of one SSRI to another. Citalopram compared with escitalopram One multicenter study randomized 366 patients with panic disorder to citalopram (10-40 mg/d), 190 escitalopram (5-20 mg/d), or placebo. Patients with and without concomitant agoraphobia were included. Quality of life and health-related functional capacity were additional outcome measures. The frequency of panic attacks was significantly reduced for escitalopram compared to placebo (P=0. Both treatments significantly improved quality of life, panic disorder symptoms, and severity of the disease (P<0. The article does not report a direct comparison of citalopram to escitalopram; presumably the two active treatment groups did not differ significantly on efficacy measures. Sertraline compared with paroxetine A German RCT randomized 225 patients with panic disorder to paroxetine (40-60 mg/d) or 192 sertraline (50-150 mg/d). Patients with and without concomitant agoraphobia were included. Quality of life was assessed as a secondary outcome measure. Results revealed no statistically significant differences in PAS (Panic and Agoraphobia Scale) scores between treatment groups (P=0. Furthermore, no statistical differences in secondary outcome measures (PAS subscales, CGI-S, HAM-A, Sertraline-Quality of Life Battery) could be detected. Citalopram compared with paroxetine A small Italian trial enrolled 58 patients to citalopram (20-50 mg/d) and paroxetine (20-50 mg/d) 191 for 60 days. Patients and care providers were not blinded to treatment allocation; therefore, this study received a poor quality rating for internal validity. Results reported no statistically significant differences between citalopram and paroxetine in any efficacy measures.
Therapeutic vaccination of HIV-1-infected patients on HAART with a recom- binant HIV-1 nef-expressing MVA: safety purchase eriacta discount 60784 impotence of organic origin, immunogenicity and influence on viral load during treatment inter- ruption generic eriacta 100mg on line erectile dysfunction ugly wife. Antivir Ther 2005; 10:285-300 Harrer T buy 100mg eriacta amex erectile dysfunction doctors in colorado springs, Harrer E, Kalams SA, et al. Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with pro- longed infection and low viral load. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. Quantification of CD8+ T lymphocytes responsive to human immunodefi- ciency virus (HIV) peptide antigens in HIV-infected patients and seronegative persons at high risk for recent HIV exposure. Human T cells expressing two additional receptors (TETAR) specific for HIV-1 provide new insights in antigen-induced TCR down-modulation. Preliminary results of safety and immunogenicity of Ad35-GRIN/ENV HIV Vaccine in HIV-uninfected subjects (IAVI B001). Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope gly- coprotein in complex with the CD4 receptor and a neutralizing human antibody. Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1. Preserved CD4+ central memory T cells and survival in vaccinated SIV-chal- lenged monkeys. Immunization with envelope subunit vaccine products elicits neu- tralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. Role of CTL-mediated immune selection in a dominant HLA-B8-restricted CTL epitope in Nef. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case—cohort analysis. Lessons learned from HIV-1 vaccine trials:new priorities and directions. Dual selection pressure by drugs and HLA class I-restricted immune responses on HIV-1 protease. The qualitative nature of the primary immune response to HIV infec- tion is a prognosticator of disease progression independent of the initial level of plasma viremia. Randomized, double-blind, placebo-controlled efficacy trial of a biva- lent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. Extended evaluation of the virologic, immunologic, and clini- cal course of volunteers who acquiredHIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX(R) B/E. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 2013; 503:277-280 Wagner R, Leschonsky B, Harrer E, et al. Molecular and functional analysis of a conserved CTL epitope in HIV-1 p24 recognized from a long-term nonprogressor: constraints on immune escape associated with targeting a sequence essential for viral replication. Acute HIV-1 Infection HENDRIK STREECK AND MARCUS ALTFELD Introduction Within days of HIV-1 acquisition, a transient symptomatic illness associated with high levels of HIV-1 replication and rapid loss of CD4 cells occurs. This highly dynamic phase is accompanied by clinical symptoms similar to mononucleosis. However, despite an estimate of 6,000 new HIV-1 transmissions per day (UNAIDS 2013 Global Report), the diagnosis is missed in the majority of cases. The diagnosis requires a high degree of awareness and clinical knowledge based on clinical symptoms and history of exposure, in addition to specific laboratory tests (detection of HIV-1 RNA or p24 antigen and negative HIV-1 antibodies). An accurate diagnosis of HIV-1 infection during this early stage of infection is par- ticularly important as about 50% of new sexual transmissions are estimated to happen while a person is in this primary phase of infection (Brenner 2007). Indeed, phylo- genetic analyses demonstrate a clustering of infections during primary HIV-1 infec- tion, and the catalytic effect of acute HIV-1 infection on the HIV pandemic could be prevented or at least slowed by early diagnosis and immediate antiretroviral therapy intervention (see below). The potentially beneficial use of antiretroviral therapy as pre-exposure prophylaxis (PrEP) could change the face of acute HIV-1 infection in the future (see ART chapter). Recent studies conducted in South Africa, Europe and the US have demonstrated that the use of tenofovir or tenofovir gel might significantly protect from HIV infection (Cohen 2011, Karim 2011). It has been demonstrated that new HIV infections can be reduced by up to 86% (confi- dence interval 40–99%) in individuals at high risk (IperGAY study, www. While no resistant breakthroughs have been detected so far, it is currently unknown how much risk of increased viral resistance due to this monotherapeutic use of anti- retroviral medication although it has not been seen to date except in people who were probably serconverting near the time of starting PrEP. Moreover, it is unknown whether other antiretrovial medications or longer-acting formulations may be better suited as PrEP. Definition and classification Acute HIV-1 infection (AHI) is defined by high levels of plasma HIV-1 RNA in the presence of a negative anti-HIV-1 ELISA and/or negative/indeterminate Western Blot (<3 bands positive) documenting the evolving humoral immune response; whereas early HIV-1 infection (EHI) includes anyone with documentation of being HIV-1 antibody negative in the preceding 6 months and is therefore broader than the definition of acute HIV-1 infection. Both are included in the term primary HIV-1 infection (PHI) (see Figure 1). A more detailed classification system of the early phases of HIV infection is now in use (Fiebig 2003), which has little relevance for clinical decisions but is important for scientific purposes. The definition used influences the methods needed to make the diagnosis and any considerations regarding the path- ogenic implications of this stage of disease. Acute HIV-1 infection is often associated with an acute “retroviral syndrome” that usually includes fever with a variety of non- specific clinical and laboratory abnormalities. In contrast, subjects with early HIV-1 infection can be asymptomatic. The time from exposure to symptomatic disease is Acute HIV-1 Infection 53 Figure 1: Fiebig stages of acute HIV infection typically 2 to 4 weeks, and the duration of illness is generally days to weeks. Identifying patients with this syndrome requires a thorough risk assessment, recog- nition of the variable clinical and laboratory manifestations, and understanding what tests need to be performed in order to make the diagnosis. Signs and symptoms After an incubation period ranging from a few days to a few weeks after exposure to HIV, infected individuals often present with an acute flu-like illness. Acute HIV-1 infection is a very heterogeneous syndrome and individuals presenting with more severe symptoms during acute infection and a longer duration of the acute infec- tion syndrome tend to progress more rapidly to AIDS (Vanhems 1998, Pedersen 1989, Keet 1993).
There is one case report of the development of K70E and M184V during therapy with TDF and FTC buy generic eriacta 100 mg on-line erectile dysfunction doctors in colorado, which were then replaced by K70G and M184V buy eriacta 100 mg with visa erectile dysfunction by age statistics. Both mutations were located on the same genome and conferred phenotypic resistance to all NRTIs except for AZT or d4T (Bradshaw 2007) buy eriacta now impotence nasal spray. M184V as well as the L74V mutation and the NNRTI-specific mutations, L100I and Y181C, may have an antagonistic effect on the further development of resistance (Vandamme 1999, Underwood 2005). M184V induces resensitization to AZT and d4T, resulting in a reduction of IC50 by 50 and 30%, respectively. L74V/I with or without M184V leads to a reduction in IC50 of about 70%. However, resensitization is of clinical relevance only if there are no more than three other AZT- or d4T-associated mutations (Underwood 2005). The M184V mutation also increases sensitivity to TDF (Miller 2001, Miller 2004). In contrast, the presence of M184V plus multiple NAMs or mutations at positions 65, 74 or 115 increase resistance to ABC (Harrigan 2000). So-called multidrug resistance (MDR) to all NRTIs – except 3TC and probably FTC, is established with T69SSX, i. The T69SSX insertion induces an approximately 20-fold increase in resistance to TDF (Miller 2001+2004). Q151M alone leads to intermediate resistance to AZT, d4T, ddI and ABC and involves only a minor loss of TDF activity. Q151M combined with mutations at positions 75, 77 and 116 confers high-grade resistance to AZT, ddI, d4T and ABC and intermediate resistance to TDF. The insertion T69SSX together with the mutation M184V, as well as the mutation Q151M together with M184V, leads to a 70% reduction in viral replication capacity (Miller 2003, White 2004). Complete resistance to TDF is caused by the simultane- HIV Resistance and Viral Tropism Testing 311 ous presence of the Q151M complex in combination with K70Q (Hachiya 2011). TAF (tenofovir alafenamide), like TDF (tenofovir disoproxil fumarate), is a tenofovir prodrug. In vitro data suggest that by reaching 5-fold higher intracellular levels of the active substance, the use of TAF may overcome NRTI-resistant viruses (Margot 2013). In large patient cohorts, quantitative measurements of sensitivity have shown that up to 29% of NRTI-experienced patients have a hypersusceptibility to NNRTIs (i. A reduction in AZT or 3TC sensitivity correlates inversely with an increased NNRTI susceptibility (Shulman 2000). The reverse transcriptase mutations T215Y, H208Y and V118I seem predictive for efavirenz hypersusceptibility. This is also true for non-thymidine analog-associated NAMs like K65R, T69X, M184V and in particular for the combi- nation K65R+M184V (Whitcomb 2000, Shulman 2004, Coakley 2005a). However, these results have not influenced treatment strategies. NNRTIs First generation NNRTIs Several mutations have been described with first-generation NNRTIs such as efavirenz and nevirapine. A single mutation can confer high-level resistance, in particular K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S for nevirapine and L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S for efavirenz (Melikian 2014). Contrary to V106A, V106M is seen more frequently with subtype C as with subtype B viruses (Grossmann 2004). Nevirapine or efavirenz should be stopped in the presence of mutations as the selection of further RAMs may compromise the efficacy of second generation NNRTIs. Second generation NNRTIs Etravirine is effective against variants with single NNRTI mutations like K103N, Y188L and/or G190A (Andries 2004, Vingerhoets 2010). Compared to earlier NNRTIs, etravirine has a higher genetic barrier, probably due to flexible binding to the reverse transcriptase site. In a selection experiment, the dominant viral population harbo- red, after several in vitro passages, the mutations V179F (a new variant at this posi- tion) and Y181C. Other mutations that have been selected in vitro are L100I, E138K, Y188H, G190E, M230L, and V179I (Brilliant 2004, Vingerhoets 2005). Similarly, V179F, V179I and Y181C were seen with virologic failure in the DUET studies. Further RAMs were noted at positions 101 and 138 (Tambuyzer 2010). Using a regression model and a data set of 519 geno-/phenotype pairs, 5 key mutations at 4 positions could be identified: K101P, Y181I/V, G190E and F227C. In addition, K101H, E138G, V179F and M230L proved to be relevant (Melikian 2014). In the DUET studies, 17 RAMs for etravirine were identified: V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S and M230L. Based on these, an etravirine resistance score was developed. A weighting factor of 3 was attrib- uted to Y181I/V, followed by a weighting factor of 2. The mutations E138A, V106I, G190S, and V179F received a weighting factor of 1. In a panel of 4,248 NNRTI-resistant clinical HIV-1 isolates, the mutations with the highest weight, Y181I and Y181V, had a low prevalence of 1. The mutation Y181C, which is selected more frequently in patients taking nevirapine than efavirenz, had a prevalence of 32% (Vingerhoets 2008). E138A/G, V179E, G190Q, M230L and K238N received 3 points; 101E, V106A / I, E138K, V179L, Y188L and G190S received 2 points. V90I, A98G, K101H, K103R, V106M, E138Q, V179D/F/I/M/T, Y181F, V189I, G190A/E/T, H221Y, P225H, and K238T contributed with 1 point. A loss of efficacy is likely with a total score of 4 or higher (Haddad 2010). Rilpivirine is also effective against single NNRTI RAMs such as K103N, V106A, G190S/A; in vitro the following mutations were selected: V90I, L100I, K101E, V106A/I, V108I, E138G/K/Q/R, V179F/I, Y181C/I, V189I, G190E, H221Y, F227C and M230I/L (Azijn 2009). In a clinical study involving treatment-naïve patients without any (known) NNRTI mutations most of the in vitro mutations were confirmed (K101E, K103N, E108I, E138K/R, Y181C und M230L) (Molina 2008). The cross-resistance between rilpivirine and etravirine is greater than 90% (Porter 2013). Six key muta- tions at 5 positions could be identified for rilpivirine using a data set of 187 geno-/ phenotype pairs: L100I, K101P, Y181I/V, G190E and F227C. Similar to etravirine, K101H, E138G, V179F and M230L were further relevant mutations (Melikian 2014). In the Phase III studies ECHO und THRIVE, virological failure was more frequent on rilpivirine than on efavirenz (10. RAMs were more common in patients failing on rilpivirine than on efavirenz (63% versus 54%). The most common mutations were E138K (45%), K101E (13%), H221Y (10%), V189I (8%), Y181C (8%) and V90I (8%). In 46%, 31% and 23% of resistant isolates respectively, 1, 2 or 3 NNRTI mutations were detected.