Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. RESULTS: Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. CONCLUSIONS: The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.

Out of focus: tailoring the cascade of care to the needs of women living with HIV.

Around half of the global adult HIV-positive population are women, yet historically women have been under-represented in clinical studies of antiretroviral therapy (ART) and there has been minimal exploration of gender-specific factors related to the response to and appropriateness of treatment choices in women living with HIV (WLWH). There are several key issues pertaining to the cascade of HIV care that make it important to differentiate WLWH from men living with HIV. Factors that are gender specific may impact on the status of WLWH, affecting access to diagnosis and treatment, optimal clinical management, ART outcomes, retention in care, and the overall long-term wellbeing of WLWH. In this review, we discuss the results of recently reported women-only clinical trials and highlight the key unmet needs of WLWH as they pertain to the cascade of HIV care across World Health Organization European Region countries. As significant knowledge gaps remain, the review identifies key areas where further research is required, in order to support improved management of WLWH and guide informed clinical decision-making, including addressing psychosocial factors as part of comprehensive care.

Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.

OBJECTIVES: Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS: Resistance tests conducted in antiretroviral treatment (ART)-naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS: TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naïve. CONCLUSIONS: We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.

Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants.

Plasma drug-resistant minority human immunodeficiency virus type 1 variants (DRMVs) increase the risk of virological failure to first-line non-nucleoside reverse transcriptase inhibitor antiretroviral therapy (ART). The origin of DRMVs in ART-naive patients, however, remains unclear. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). Here, we evaluated if such DRMVs could have emerged from apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3G/F (APOBEC3G/F) activity. Out of 236 ART-naive subjects evaluated, APOBEC3G/F hypermutation signatures were detected in plasma viruses of 14 (5.9%) individuals. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P < 0.005), defined as the presence of > 0.5% of sample sequences with an APOBEC3G/F signature. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. In-frame STOP codons were observed in 1.5% of all clonal sequences; 14.8% of them co-occurred with APOBEC3G/F signatures. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. In a re-analysis of the parent case control study, the presence of APOBEC3G/F signatures was not associated with virological failure. In conclusion, the contribution of APOBEC3G/F editing to the development of DRMVs is very limited and does not affect the efficacy of non-nucleoside reverse transcriptase inhibitor ART.

Detection of the NS3 Q80K polymorphism by Sanger and deep sequencing in hepatitis C virus genotype 1a strains in the UK.

The Q80K polymorphism in the hepatitis C virus (HCV) NS3 enzyme reduces susceptibility to simeprevir and other novel protease inhibitors. The aims of this study were to determine the prevalence of Q80K in treatment-naïve HCV-1a carriers in the North West region (NW) and South East region (SE) of England, investigate the occurrence of Q80K as a minority variant, and characterize viral phylogeny. Plasma samples from subjects who were naïve to anti-HCV therapy were subjected to conventional (Sanger) and deep (Illumina-Miseq, 1% interpretative cut-off) sequencing of NS3. Q80K occurred in 44 of 238 subjects (18.5%, 95% CI 13.6-23.4%), including 19 of 70 (27.1%) in the NW and 25 of 168 (14.9%) in the SE (p 0.0425), with no difference in HCV RNA load or human immunodeficiency virus (HIV) status. Q80K frequencies in reads of samples subjected to Illumina sequencing were >40% in all cases. Among subjects with Q80K, five of 44 (11.4%) showed one additional major resistance-associated mutation in NS3, detected at frequencies of >10% (V36L and V55A) or <10% (V36M). Phylogenetic analyses identified the two recognized HCV-1a lineages with (clade I) and without (clade II) Q80K. Overall, 148 of 238 (62.2%) sequences occurred within regional or inter-regional clusters, each comprising 3-20 sequences. There was no unique clustering of English sequences relative to strains from continental Europe and North America. In conclusion, Q80K was found at a high prevalence among treatment-naïve HCV-1a carriers in England, and was reliably detected by conventional sequencing, with no increased detection by deep sequencing. English sequences were highly interspersed with sequences from elsewhere in Europe (clade II) and North America (clade I), and their phylogeny was consistent with multiple introductions from different areas.

Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use of resistance testing in START trial participants. METHODS: In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. RESULTS: Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1.8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, the prevalence of TDR was highest in Australia (17.5%), France (16.7%), the USA (12.6%) and Spain (12.6%). No participant characteristics were identified as predictors of the presence of TDR. CONCLUSIONS: START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the USA and Australia, TDR prevalence rates varied by country.

Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.

HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.

Occult hepatitis B virus coinfection in HIV-positive African migrants to the UK: a point prevalence study.

OBJECTIVES: Occult (surface antigen-negative/DNA-positive) hepatitis B virus (HBV) infection is common in areas of the world where HBV is endemic. The main objectives of this study were to determine the prevalence of occult HBV infection in HIV-infected African migrants to the UK and to determine factors associated with occult coinfection. METHODS: This anonymized point-prevalence study identified Africans attending three HIV clinics, focussing on patients naïve to antiretroviral therapy (ART). Stored blood samples were tested for HBV DNA. Prevalence was calculated in the entire cohort, as well as in subpopulations. Risk factors for occult HBV coinfection were identified using logistic regression analysis. RESULTS: Among 335 HIV-positive African migrants, the prevalence of occult HBV coinfection was 4.5% [95% confidence interval (CI) 2.8-7.4%] overall, and 6.5% (95% CI 3.9-10.6%) and 0.8% (95% CI 0.2-4.6%) in ART-naïve and ART-experienced patients, respectively. Among ART-naïve anti-HBV core (anti-HBc)-positive patients, the prevalence was 16.4% (95% CI 8.3-25.6%). The strongest predictor of occult coinfection was anti-HBc positivity [odds ratio (OR) 7.4; 95% CI 2.0-27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range (IQR) 33-513 IU/mL] and 22 U/L (IQR 13-27 U/L), respectively. CONCLUSIONS: Occult HBV coinfection remains under-diagnosed in African HIV-infected patients in the UK. Given the range of HBV DNA levels observed, further studies are warranted to determine its clinical significance and to guide screening strategies and ART selection in these patients.

Outcomes of starting first-line antiretroviral therapy in hepatitis B virus/HIV-coinfected patients in Ghana.

OBJECTIVES: HIV/hepatitis B virus (HBV) coinfection is common in Ghana, where first-line antiretroviral therapy (ART) comprises lamivudine with zidovudine or stavudine and nevirapine or efavirenz. Little is known about ART outcomes in the context of coinfection. This study evaluated outcomes of ART among HIV/HBV-coinfected Ghanaians, focusing on locally available parameters. PATIENTS AND METHODS: An observational study comparing clinical and virological outcomes in HIV-infected individuals who were either hepatitis B surface antigen (HBsAg) positive or HBsAg negative was conducted over 36 months. Clinical events, hepatic transaminases, CD4 count and body mass index (BMI) were evaluated among 143 HBsAg-positive and 228 HBsAg-negative patients. In a random subset of HBsAg-positive patients, HBV-DNA levels and polymerase sequences were analysed. RESULTS: Comparing HBsAg-positive and HBsAg-negative patients, 44/143 (30.8%) and 83/228 (36.4%) defaulted follow-up, 15/143 (10.5%) and 30/228 (13.2%) experienced a new clinical event, and 8/143 (5.6%) and 11/228 (4.8%) discontinued their initial regimen, respectively. Transaminase levels were higher in HBsAg-positive patients, although elevations were low grade. HBV coinfection was associated with an adjusted 2.04 (95% CI 0.59-3.49) cells/mm(3)/month smaller CD4 cell increase; there was no significant effect on BMI changes. After a median of 9 months of ART, 64/66 (97.0%) patients showed detectable HBV-DNA (median 3.3 log(10) IU/mL; IQR 2.6-6.2); 12/53 (22.6%) of these showed lamivudine-associated resistance mutations. CONCLUSIONS: HIV/HBV-coinfected Ghanaians tolerated first-line ART well, but experienced blunted CD4 cell responses. There was evidence of ongoing HBV replication, mild but persistent transaminase elevations and emerging lamivudine resistance in a proportion of treated patients, indicating the potential for progressive liver damage.

Patterns of HIV testing at a London teaching hospital between 2004 and 2007.

The aims of this study were to observe trends in testing for HIV between 2004 and 2007 in one London, UK, hospital and to observe the seroprevalence of HIV within subgroups. Tests were grouped according to source and reason for testing. A total of 58,720 tests were considered (HIV-1 seroprevalence 0.9%). The majority (75.4%) of tests were performed as part of routine and opt-out protocols including antenatal and genitourinary (GU) screening. Among people specifically seeking HIV testing, the HIV seroprevalence was 3.5%. Medical specialties performed fewer tests but a high HIV seroprevalence was observed, including infectious disease (seroprevalence 4.4%) and other medical specialties (seroprevalence 3.4%). A small number of specialties performed few HIV tests. HIV testing was cost-effective in virtually all settings. This study suggests that more HIV tests could be performed, for example, in acute medicine, and training might increase the number of tests offered in some settings. The most effective way of increasing testing appears to be opt-out testing.

Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA.

OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. RESULTS: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). CONCLUSIONS: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.

Patterns of HIV testing at a London teaching hospital between 2004 and 2007.

To observe trends in testing for HIV between 2004 and 2007 in a London hospital and to observe the seroprevalence of HIV within subgroups. Tests were grouped according to source and reason for testing; 58,720 tests were considered (HIV-1 seroprevalence = 0.9%). The majority (75.4%) of tests were performed as part of routine and opt-out protocols including antenatal and genitourinary screening. Among people specifically seeking HIV testing, the HIV seroprevalence was 3.5%. Medical specialties performed fewer tests but a high HIV seroprevalence was observed, including infectious disease (seroprevalence 4.4%) and other medical specialties (seroprevalence 3.4%). A small number of specialties performed few HIV tests. HIV testing was cost-effective in virtually all settings. This study suggests that more HIV tests could be performed, for example, in acute medicine, and training might increase the number of tests offered in some settings. The most effective way of increasing testing appears to be opt-out testing.

European guidelines on the clinical management of HIV-1 tropism testing.

Viral tropism is the ability of viruses to enter and infect specific host cells and is based on the ability of viruses to bind to receptors on those cells. Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. In most European countries, HIV tropism is identified with tropism phenotype testing. New data support genotype analysis of the HIV third hypervariable loop (V3) for the identification of tropism. The European Consensus Group on clinical management of tropism testing was established to make recommendations to clinicians and clinical virologists. The panel recommends HIV-tropism testing for the following groups: drug-naive patients in whom toxic effects are anticipated or for whom few treatment options are available; patients who have poor tolerability to or toxic effects from current treatment or who have CNS pathology; and patients for whom therapy has failed and a change in treatment is considered. In general, an enhanced sensitivity Trofile assay and V3 population genotyping are the recommended methods. Genotypic methods are anticipated to be used more frequently in the clinical setting because of their greater accessibility, lower cost, and faster turnaround time than other methods. For the interpretation of V3 loop genotyping, clinically validated systems should be used when possible. Laboratories doing HIV tropism tests should have adequate quality assurance measures. Similarly, close collaboration between HIV clinicians and virologists is needed to ensure adequate diagnostic and treatment decisions.

Modelling response to HIV therapy without a genotype: an argument for viral load monitoring in resource-limited settings.

In the absence of widespread access to individualized laboratory monitoring, which forms an integral part of HIV patient management in resource-rich settings, the roll-out of highly active antiretroviral therapy (HAART) in resource-limited settings has adopted a public health approach based on standard HAART protocols and clinical/immunological definitions of therapy failure. The cost-effectiveness of HIV-1 viral load monitoring at the individual level in such settings has been debated, and questions remain over the long-term and population-level impact of managing HAART without it. Computational models that accurately predict virological response to HAART using baseline data including CD4 count, viral load and genotypic resistance profile, as developed by the Resistance Database Initiative, have significant potential as an aid to treatment selection and optimization. Recently developed models have shown good predictive performance without the need for genotypic data, with viral load emerging as by far the most important variable. This finding provides further, indirect support for the use of viral load monitoring for the long-term optimization of HAART in resource-limited settings.

Use of a prescription-based measure of antiretroviral therapy adherence to predict viral rebound in HIV-infected individuals with viral suppression.

OBJECTIVE: The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients. METHODS: The analysis was performed on the Royal Free HIV Cohort, London, UK. Each 'drug coverage-viral load episode' (DCVL episode) was defined as a 6-month period immediately prior to a VL < or =50 HIV-1 RNA copies/mL (time-zero), during which the patient had been continuously on HAART, with all measured VLs < or =50 copies/mL. The next VL after time-zero was used to assess whether VL rebound (defined as >200 copies/mL) had occurred. Drug coverage, our measure of adherence, was calculated as the proportion of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs. RESULTS: A total of 376 (2.4%) VL rebounds occurred in 15 660 DCVL episodes among 1632 patients. Drug coverage was 100% for 32% of episodes, 95-99% for 16% of episodes and < or =60% for 10% of episodes. The risk ratio of rebound associated with a 10% increase in drug coverage, adjusted for potential confounding variables, was 0.93 (95% confidence interval 0.88-0.98). CONCLUSIONS: Antiretroviral drug coverage assessed at the time of VL measurement in patients with undetectable VL is potentially clinically useful for predicting VL rebound at the next VL measurement.

Herpes simplex virus type 2: epidemiology and management options in developing countries.

Genital herpes simplex virus type 2 (HSV2) is highly prevalent worldwide and an increasingly important cause of genital ulcer disease (GUD). Continued HSV2 transmission is facilitated by the large number of undiagnosed cases, the frequency of atypical disease and the occurrence of asymptomatic shedding. The lack of easy, affordable diagnostic methods and specific antiviral treatment in countries with low and middle income is of great concern, given the ability of GUD to enhance HIV transmission and acquisition. With rising HSV2 prevalence contributing to an increase in the proportion of GUD attributed to genital herpes in high-HIV prevalence settings, a safe and effective HSV vaccine is urgently needed. Meanwhile, multifaceted interventions are required to improve recognition of genital herpes, to prevent its spread and also to prevent its potential to promote HIV transmission in developing countries.

Genotypic antiretroviral drug resistance testing at low viral loads in the UK.

BACKGROUND: Antiretroviral drug resistance testing is recommended in HIV-1 infected patients failing therapy in order to inform treatment selection. Although guidelines and test manufacturers recommend a viral load of at least 500-1000 HIV-1 RNA copies/mL for genotypic resistance testing to be performed, prompt management of virological failure could benefit from testing at lower viral load levels. METHODS: Laboratories undertaking genotypic resistance testing were asked to provide figures for the number of resistance tests undertaken at viral loads <2000 copies/mL, the success rates of such tests and the extent of resistance detected, all stratified for viral load levels. RESULTS: Of the replies received, most laboratories were attempting resistance testing at viral loads below the recommended guidelines, with variable success and outcomes. CONCLUSIONS: This audit of current practice in the UK for undertaking genotypic resistance tests at viral loads <1000 copies/mL highlights the widespread use of such testing outside the British HIV Association guidelines.