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V Miller

Publications and source records attributed to V Miller.

At least 19 recordsLinked to original sources
PubMed2006

Endocrine, luteal and follicular responses after the use of the short-term protocol to synchronize ovulation in goats.

The effect of the so-called Short-Term Protocol (5-day progesterone treatment+PGF(2)alpha) on ovarian activity and LH surge was studied in goats. The goats received 250IU eCG at the time of device withdrawal (eCG group; n=7), or 200microg of EB (estradiol benzoate) 24h after device withdrawal (EB group; n=8), or received neither eCG nor EB (control group; n=8). The Short-Term Protocol induced greater (4.1+/-1.1ng/ml) progesterone serum concentrations at 24h after start of the treatment, that declined to 0.2+/-0.1ng/ml at 12h after device withdrawal. In all of the groups, the maximum concentration of estradiol-17beta was reached at about 36h after device withdrawal. Maximum concentration was greater in the EB group (76.9+/-24.6pmol/l) than in the control group (41.8+/-9.0pmol/l; P<0.01), with the eCG group showing intermediate concentration (70.3+/-32.5pmol/l; P=NS). The LH peak occurred earlier in the eCG group (38.4+/-2.0h after device withdrawal) and in the EB group (41.0+/-4.1h), than in the control group (46.3+/-5.1h; P<0.05). Ovulation occurred earlier in the eCG group (5/7) and in the EB group (8/8) (58.8+/-2.7h and 63.0+/-5.6h, respectively), than in the control group (7/8) (70.2+/-8.3h; P<0.05). In summary, the Short-Term Protocol induced similar concentrations of progesterone among treated goats. In addition, eCG or EB resulted in a similar increase in estradiol-17beta and a similar LH surge, which induced ovulation in most females (86.7%) in a consistent interval (about 60h) after the end of progesterone exposure.

Animals↗
PubMed2006

Bran and irritable bowel syndrome: the primary-care perspective.

BACKGROUND: We have shown that bran exacerbates irritable bowel syndrome symptoms in a large proportion of secondary-care patients. However, it is unknown if this also happens in primary-care or whether a better response to bran occurs, leading to bran failures being selected for referral to the specialist. AIMS: To assess the response to bran in primary-care irritable bowel syndrome comparing it to that obtained in secondary-care. PATIENTS AND METHODS: One hundred consecutive primary-care irritable bowel syndrome patients were asked how bran or soluble fibre products affected their symptoms. RESULTS: Bran improved symptoms in 27% of primary-care and 10% of secondary-care patients (p<0.01) and exacerbated symptoms in 22% of primary-care and 55% of secondary-care patients (p<0.001). Fifty-one percent of primary-care and 33% of secondary-care patients reported no change with bran. In primary-care, proprietary fibre led to improvement in 25%, deterioration in 19% and no change in 56% which was not significantly different to secondary-care. CONCLUSION: Although not especially effective in primary-care irritable bowel syndrome patients, bran does not cause so many problems and is more helpful than in secondary-care. The effects of soluble fibre are similar in both primary-care and secondary-care. This study highlights the problem of extrapolating the response to treatment in irritable bowel syndrome from different care settings.

Adult↗
PubMed2006

Treatment of non-cardiac chest pain: a controlled trial of hypnotherapy.

BACKGROUND: Non-cardiac chest pain (NCCP) is an extremely debilitating condition of uncertain origin which is difficult to treat and consequently has a high psychological morbidity. Hypnotherapy has been shown to be effective in related conditions such as irritable bowel syndrome where its beneficial effects are long lasting. AIMS: This study aimed to assess the efficacy of hypnotherapy in a selected group of patients with angina-like chest pain in whom coronary angiography was normal and oesophageal reflux was not contributory. PATIENTS AND METHODS: Twenty eight patients fulfilling the entry criteria were randomised to receive, after a four week baseline period, either 12 sessions of hypnotherapy or supportive therapy plus placebo medication over a 17 week period. The primary outcome measure was global assessment of chest pain improvement. Secondary variables were a change in scores for quality of life, pain severity, pain frequency, anxiety, and depression, as well as any alteration in the use of medication. RESULTS: Twelve of 15 (80%) hypnotherapy patients compared with three of 13 (23%) controls experienced a global improvement in pain (p = 0.008) which was associated with a significantly greater reduction in pain intensity (p = 0.046) although not frequency. Hypnotherapy also resulted in a significantly greater improvement in overall well being in addition to a reduction in medication usage. There were no differences favouring hypnotherapy with respect to anxiety or depression scores. CONCLUSION: Hypnotherapy appears to have use in this highly selected group of NCCP patients and warrants further assessment in the broader context of this disorder.

Anxiety↗
PubMed2006

Carotid sinus hypersensitivity associated with focal alpha-synucleinopathy of the autonomic nervous system.

A case of an 82-year-old woman who experienced repeated falls is described. She exhibited a cardioinhibitory carotid sinus hypersensitivity after right carotid sinus massage (CSM), but without evidence of orthostatic hypotension. After a pacemaker was implanted, she did not experience any falls, dizziness or syncope. Her balance eventually deteriorated, but she remained cognitively intact and died from lung cancer at the age of 89 years. Neuropathological examination showed only age-related Alzheimer's disease pathology and a few alpha-synuclein-positive granular deposits and neurites in the dorsal nucleus of the vagus and solitary tract nucleus in the medulla, but a marked alpha-synuclein pathology in the stellate ganglia. The cardioinhibitory element of her CSM was possibly because of the alpha-synuclein pathology in the ganglion, which impaired sympathetic transmission. This case shows another phenotype among patients with alpha-synucleinopathy.

Accidental Falls↗
PubMed2005

The Protease Inhibitor Transfer Study (PROTRA 1): abacavir and efavirenz in combination as a substitute for a protease inhibitor in heavily pretreated HIV-1-infected patients with undetectable plasma viral load.

OBJECTIVES: The aim of the study was to evaluate the safety and efficacy of abacavir (ABC) and efavirenz (EFV) instead of a protease inhibitor (PI) in HIV-1-infected subjects treated with two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI with undetectable viral loads (< 50 HIV -1 RNA copies/mL). To be eligible for inclusion, patients had to have a history of viral load < 400 copies/mL for at least 3 months and had to be naive to treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs) and ABC, but multiple pretreatment and treatment failure were allowed. DESIGN: An open-label, single-centre pilot study of duration 48 weeks was conducted. ABC was added to the original treatment with two NRTIs and one PI at baseline, and at week 6 the PI was replaced by EFV. At each study visit, CD4 cell count, viral load [measured by polymerase chain reaction (PCR)] and clinical chemistry were measured. Fasting blood samples were taken at baseline and at weeks 12, 24, 36 and 48 to measure levels of cholesterol [high-density lipoprotein (HDL)/low-density lipoprotein (LDL)], triglycerides, insulin and C-peptide. Additionally, an oral glucose tolerance test (OGTT) was performed. A bioelectric impedance analysis (BIA) and a single slice abdominal and mid-thigh computed tomography (CT) scan were carried out to assess changes in body composition. RESULTS: Thirty patients were included in the study. Three patients experienced ABC-hypersensitivity and one patient demonstrated virological failure caused by nonadherence. At week 48, all remaining patients had viral loads < 50 copies/mL with stable CD4 counts. The fasting metabolic parameters and abdominal fat distribution remained unchanged. CONCLUSIONS: In heavily pretreated patients, ABC and EFV in combination provide an effective, simplified and well-tolerated alternative to PI treatment.

Adult↗
PubMed2004

Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans.

Impairments in early information processing are a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and Alzheimer's disease (AD). Several lines of evidence implicate a dysfunction of the cholinergic system in these disorders, particularly in AD where there is known degeneration in major cholinergic pathways. Inspection time (IT), a measure of early visual information processing speed, has been shown to be sensitive to cholinergic manipulation. The current study employed the IT task to (1) examine the independent roles of nicotinic and muscarinic receptors in modulating information processing and (2) investigate the interaction of nicotinic and muscarinic receptor systems in modulating information processing. Twelve healthy participants completed a randomized, double-blind, placebo-controlled study under four drug conditions; (1) placebo, (2) mecamylamine (15 mg; oral), (3) scopolamine (0.4 mg, s.c.), (4) mecamylamine (15 mg) + scopolamine (0.4 mg). IT measures were examined at baseline and 2.5 h post drug administration. Selective blockade of nicotinic receptors with mecamylamine did not significantly impair IT, whereas selective blockade of muscarinic receptors with scopolamine produced a significant but small impairment in IT. Combined blockade of both receptor types with scopolamine and mecamylamine produced a large impairment in IT performance. The results indicate that both nicotinic and muscarinic receptors are involved in modulating IT, and that the two systems may function synergistically to modulate early visual information processing. These findings suggest that functional abnormalities in both nicotinic and muscarinic systems may underlie deficits in early visual information processing seen in disorders such as Alzheimer's disease and schizophrenia.

Adult↗
PubMed2004

Prostaglandin F2alpha treatment associated with timed artificial insemination in ewes.

Traditional treatments of two prostaglandin F2 alpha (PGF2alpha) doses at 10-day intervals or more did not result in acceptable pregnancy rates in timed artificial insemination (TAI) programmes in ewes. An explanation might be the undefined time-period of the onset of oestrus and ovulation after the treatment. Recently a consistent interval to oestrus and ovulation was obtained by giving PGF2alpha at day 3 post-ovulation, i.e. when the largest follicle of the first follicular wave of the cycle was still growing. This can be achieved when a second dose of PGF2alpha is given 7 days after a first dose. In this work, we evaluated the synchronization of oestrus and determined which of three different moments of TAI was the most successful using a PGF2alpha (PG-7d) protocol in a large flock. A total of 436 nulliparous and multiparous ewes were treated with two doses of a PGF2alpha analogue (delprostenate 160 microg, i.m.) separated by 7 days. Onset of oestrus was recorded twice a day and a single cervical TAI with fresh undiluted semen was performed either at 42 h (n = 152), 48 h (n = 120), or 54 h (n = 164), after the second PGF2alpha dose without taking into account the oestrous response. Pregnancy rate was determined by transrectal ultrasonography 30 days after insemination. Onset of oestrus was detected in 308 of 328 and 89 of 108 multiparous and nulliparous ewes, respectively (p < 0.001), within 72 h after treatment. The distribution of the onset of oestrus did not differ between multiparous and nulliparous ewes and the highest proportion of ewes in oestrus was detected between 25 to 48 h (313/397) from the second PGF2alpha dose. The pregnancy rate in ewes inseminated at 42 h tended to be higher than those inseminated at 48 h (p = 0.09) and was higher than those inseminated at 54 h (p < 0.05) (56/152, 31/120, 37/164; respectively). Therefore, the use of the PG-7d protocol resulted in a very high synchronization of oestrus with the highest concentration (around 80%) between 25 to 48 h from the end of treatment. The best pregnancy rate (37%) was obtained after a single cervical TAI with fresh semen at 42 h.

Animals↗
PubMed2004

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗
PubMed2003

HPLC method with UV detection for evaluation of digoxin tablet dissolution in acidic medium after solid-phase extraction.

A simple and reliable method for the evaluation of dissolution of digoxin tablets in 0.01 M hydrochloric acid was developed. Digoxin and its degradation products after solid-phase extraction using C18 Sep-Pak cartridges were evaluated. Analyses were performed on C18 column (LiChrospher RP-18e, 5 microm, 125 x 4.0 mm), as mobile phase water and acetonitrile (72:28, v/v) were used. Detection wavelength was 218 nm. Identity of digoxin degradation products was confirmed by HPLC-MS.

Algorithms↗
PubMed2003

Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome.

BACKGROUND: We have previously shown that hypnotherapy alters rectal sensitivity in some patients with irritable bowel syndrome. However, this previous study used incremental volume distension of a latex balloon, which might be susceptible to subject response bias and might compromise the assessment of compliance. In addition, the study group was symptomatically rather than physiologically defined. AIM: To assess the effect of hypnotherapy on rectal sensitivity in hypersensitive, hyposensitive and normally sensitive irritable bowel syndrome patients using a distension technique (barostat) that addresses these technical issues. METHODS: Twenty-three irritable bowel syndrome (Rome I) patients (aged 24-72 years) were assessed before and after 12 weeks of hypnotherapy in terms of rectal sensitivity, symptomatology, anxiety and depression. Normal values for sensitivity were established in 17 healthy volunteers (aged 20-55 years). RESULTS: Compared with controls, 10 patients were hypersensitive, seven hyposensitive and six normally sensitive before treatment. Following hypnotherapy, the mean pain sensory threshold increased in the hypersensitive group (P = 0.04) and decreased in the hyposensitive group, although the latter failed to reach statistical significance (P = 0.19). Normal sensory perception was unchanged. Sensory improvement in the hypersensitive patients tended to correlate with a reduction in abdominal pain (r = 0.714, P = 0.07). CONCLUSION: Hypnotherapy improves abnormal sensory perception in irritable bowel syndrome, leaving normal sensation unchanged.

Abdominal Pain↗
PubMed2003

Long term benefits of hypnotherapy for irritable bowel syndrome.

BACKGROUND AND AIMS: There is now good evidence from several sources that hypnotherapy can relieve the symptoms of irritable bowel syndrome in the short term. However, there is no long term data on its benefits and this information is essential before the technique can be widely recommended. This study aimed to answer this question. PATIENTS AND METHODS: 204 patients prospectively completed questionnaires scoring symptoms, quality of life, anxiety, and depression before, immediately after, and up to six years following hypnotherapy. All subjects also subjectively assessed the effects of hypnotherapy retrospectively in order to define their "responder status". RESULTS: 71% of patients initially responded to therapy. Of these, 81% maintained their improvement over time while the majority of the remaining 19% claimed that deterioration of symptoms had only been slight. With respect to symptom scores, all items at follow up were significantly improved on pre-hypnotherapy levels (p<0.001) and showed little change from post-hypnotherapy values. There were no significant differences in the symptom scores between patients assessed at 1, 2, 3, 4, or 5+ years following treatment. Quality of life and anxiety or depression scores were similarly still significantly improved at follow up (p<0.001) but did show some deterioration. Patients also reported a reduction in consultation rates and medication use following the completion of hypnotherapy. CONCLUSION: This study demonstrates that the beneficial effects of hypnotherapy appear to last at least five years. Thus it is a viable therapeutic option for the treatment of irritable bowel syndrome.

Anxiety↗
PubMed2002

The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response.

The M184V mutation in the HIV-1 reverse transcriptase gene is primarily associated with rapid, high-level lamivudine (3TC) resistance. It has also been observed to arise under selective pressure by abacavir, to which it confers low-level resistance. Although the development of viral drug resistance remains a major concern in antiretroviral therapy, it is known that some immunological and clinical benefit can still be derived from highly active antiretroviral therapy (HAART) regimens despite resistance-associated virological failure. This residual benefit on a failing regimen is commonly attributed to the preservation of fitness-reducing protease inhibitor (PI) resistance mutations under continued drug pressure. However, fitness-reducing nucleoside reverse transcriptase inhibitor (NRTI) mutations may also contribute to the effect. M184V is both common in the treated population and fitness-reducing. A number of studies, both of dual nucleoside therapy and HAART, have noted a residual treatment effect for 3TC despite the assumed or observed presence of M184V and high-level phenotypic resistance. The speed and consistency with which this mutation is selected by 3TC under suboptimal viral suppression therefore makes M184V a particularly interesting model for further clinical studies on the association of drug resistance with ongoing treatment benefit. While fitness considerations are likely to be a major contributor to the clinical observations noted, there are a number of other potential mechanisms that may contribute to a continuing response to 3TC in the presence of M184V. These include the delay and reversal of zidovudine (ZDV) resistance, hypersensitization to other NRTIs, reduced reverse transcriptase (RT) processivity and a possible reduction in RT pyrophosphorolysis. The full impact of M184V on therapeutic prospects will require further elucidation; ideally, the risk/benefit of preserving this substitution would be investigated in randomized trials. However, existing data suggest that the presence of this mutation may preserve some benefit in spite of the loss of 3TC susceptibility which, with further study, may prove valuable.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals.

BACKGROUND: Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression. METHODS: We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy. RESULTS: A total of 61 patients experienced viral rebound during 543.1 person-years of follow-up, giving a 25.3% risk of rebound by 3.3 years from first achieving viral suppression. However, for 47 of the patients with viral rebound there was an associated documented complete interruption of antiretroviral therapy, mostly as a result of co-morbidities, leaving 14 who appear to represent a failure of the virological efficacy of therapy (viral breakthrough; 5.2% risk by 3.3 years). The risk of viral breakthrough declined with the increased duration of suppression (P = 0.01). CONCLUSION: The intrinsic virological effectiveness of multi-drug antiretroviral therapy in previously drug-naive individuals appears to be such that viral suppression, once achieved, can be maintained for several years in patients not interrupting therapy. The major challenge is to develop regimens that can be taken consistently and safely for such long periods of time.

Adult↗
PubMed2001

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.

This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox proportional hazard models. Over 26 764 person-years of prospective follow-up (PYF) from May 1994 to December 2000, the incidence of NHL decreased from 1.99 (95% confidence interval, 1.51-2.47) before September 1995 to 0.30 (0.19-0.42) cases/100 (PYF) after March 1999 (P <.001). The incidence of all subtypes of NHL decreased significantly and most pronouncedly for PBL. Among patients who started HAART, the incidence of NHL decreased from 0.88 (0.60-1.16) within the first 12 months after starting HAART to 0.45 (0.31-0.60) cases/100 PYF after more than 24 months (P =.004). In an adjusted Cox model for patients on HAART, the latest CD4 cell count and plasma viral load were both significantly associated with diagnosis of NHL; the relative hazard was 1.39 (range, 1.14-1.69) per 50% lower CD4 cell count, and 1.51 (range, 1.21-1.88) per 1 log higher plasma viral load. In conclusion, the incidence of NHL among HIV-infected patients has decreased significantly after the introduction of HAART, and the decline was most pronounced for PBL. After starting HAART, patients with insufficient immunologic and virologic responses were at highest risk of NHL.

Acquired Immunodeficiency Syndrome↗
PubMed2001

HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load.

CONTEXT: It is unclear whether delay in initiation of antiretroviral therapy (ART) may lead to a poorer viral load response for patients with human immunodeficiency virus (HIV). OBJECTIVE: To characterize the relationship of viral load response to ART with baseline CD4 cell count and baseline viral load. DESIGN: Inception cohort of 3430 therapy-naive patients with HIV, of whom 3226 patients had at least 1 viral load count after the start of ART. SETTING: Three cohort studies of patients cared for in HIV clinics in Europe between 1996 and 2000. PATIENTS: All patients initiating ART consisting of at least 3 drugs initiated in or after 1996 and for whom CD4 cell count and viral load were available in the prior 6 months (at most). MAIN OUTCOME MEASURES: Viral load decrease to below 500 copies/mL; viral load rebound to above 500 copies/mL (2 consecutive values). RESULTS: Of 3226 patients during the median follow-up of 119 weeks, 2741 (85%) experienced viral suppression to less than 500 copies/mL by 32 weeks. Relative hazards (RHs) of achieving this were 1.08 (95% confidence interval [CI], 0.98-1.21) and 0.94 (95% CI, 0.84-1.04) for baseline CD4 cell counts between 200 and 349 x 10(6)/L and baseline CD4 cell counts lower than 200 x 10(6)/L, respectively, compared with baseline CD4 cell counts of 350 x 10(6)/L or higher, after adjustment for several factors including baseline viral load. For baseline viral load, the RHs were 0.95 (95% CI, 0.84-1.07) and 0.65 (95% CI, 0.58-0.74), for 10 000 to 99 999 and 100 000 copies/mL or greater, respectively, compared with less than 10 000 copies/mL, but the probability of viral load lower than 500 copies/mL at week 32 was similar in all 3 groups. Subsequent rebound above 500 copies/mL was no more likely with a lower baseline CD4 cell count or higher viral load. CONCLUSION: In this study, lower CD4 cell counts and higher viral loads at baseline were not associated with poorer virological outcome of ART. Those with baseline viral loads of greater than 100 000 copies/mL had a slower rate of achieving viral suppression.

Adult↗
PubMed2001

Changes in seismic anisotropy after volcanic eruptions: evidence from Mount Ruapehu.

The eruptions of andesite volcanoes are explosively catastrophic and notoriously difficult to predict. Yet changes in shear waveforms observed after an eruption of Mount Ruapehu, New Zealand, suggest that forces generated by such volcanoes are powerful and dynamic enough to locally overprint the regional stress regime, which suggests a new method of monitoring volcanoes for future eruptions. These results show a change in shear-wave polarization with time and are interpreted as being due to a localized stress regime caused by the volcano, with a release in pressure after the eruption.

Journal Article↗
PubMed2001

World-wide variation in HIV-1 phenotypic susceptibility in untreated individuals: biologically relevant values for resistance testing.

OBJECTIVES: To examine the natural phenotypic variability in drug susceptibility among recombinant HIV-1 isolates from a large number of untreated HIV-positive individuals from wide-ranging geographic locations, and to use this information to establish biologically relevant cut-off values for phenotypic antiretroviral susceptibility testing. METHODS: Phenotypic susceptibility to 14 antiretroviral agents was determined for HIV-1 samples from > 1000 treatment-naive individuals in seven clinical trials. Samples were from the USA (n = 351), Germany (n = 306), Canada (n = 265), and South Africa (n = 358). Geometric mean fold-resistance and confidence intervals were determined relative to a standard laboratory wild-type virus. RESULTS: Baseline fold-resistance was approximately log-normally distributed for all antiretroviral agents examined. There was no evidence of large geographical differences in average antiviral susceptibility. Geometric mean fold-resistance for each of 14 antiviral agents was similar (+/- 0.5-fold) for samples derived from the USA, Canada, Germany, or South Africa. The non-nucleoside reverse transcriptase inhibitors (NNRTI) exhibited the broadest distribution of susceptibility; approximately 97.5% of all isolates had < 2.5-4.0, < 3.0-4.5, and < 5-10 fold-decrease in susceptibility to five protease inhibitors, six nucleoside analogues, and three NNRTI, respectively. No consistent geographic pattern or clade effect (B versus C) in either the mean or the distribution of baseline antiretroviral susceptibility was observed. CONCLUSIONS: Phenotypic drug susceptibility of HIV-1 in untreated individuals varies markedly from drug to drug, with broadly similar patterns world-wide. These results have important implications in defining the 'normal range' of phenotypic susceptibility to antiretroviral agents and establish biologically relevant cut-off values for this phenotypic drug susceptibility test.

Anti-HIV Agents↗