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1.  Short Communication: Antibody Responses to Human Immunodeficiency Virus Envelope from Infections with Multiple Subtypes Utilize the 1F7-Idiotypic Repertoire 
Abstract
A common idiotype of anti-HIV antibodies (Abs), designated as 1F7, was recently observed on anti-HIV broadly neutralizing Abs (BnAbs). The presence of the 1F7-idiotype on BnAbs suggests that continuous selection of 1F7-idiotypic Abs may allow these clones to achieve the somatic hypermutation necessary for broad neutralization. As the selection of type-specific BnAbs occurs in the setting of infections with a wide array of HIV subtypes, we investigated Abs from subjects infected with diverse subtypes for the selection of 1F7-idiotypic Abs. We observed the 1F7-idiotype on antiviral Abs in infections with various HIV subtypes. Furthermore, gp140-specific 1F7-idiotypic Abs recognized the gp140 antigens from several HIV subtypes. These results demonstrate that the 1F7-idiotype is a common characteristic of Abs from infections with diverse HIV subtypes, and suggests that early cross-reactivity of 1F7-idiotypic clones may act in conjunction with somatic hypermutation to produce BnAbs.
doi:10.1089/aid.2012.0094
PMCID: PMC3636582  PMID: 23265432
2.  Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males 
The New England journal of medicine  2011;364(5):401-411.
BACKGROUND
Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men.
METHODS
We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status.
RESULTS
In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001).
CONCLUSIONS
Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; ClinicalTrials.gov number, NCT00090285.)
doi:10.1056/NEJMoa0909537
PMCID: PMC3495065  PMID: 21288094
3.  Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee 
The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.
PMCID: PMC3142594  PMID: 22654926
Antiretrovirals; HAART; HIV; Practical guide
4.  Changes in Function of HIV-Specific T-Cell Responses with Increasing Time from Infection 
Viral Immunology  2010;23(2):159-168.
Abstract
Recently HIV-infected individuals have virus-specific responses characterized by IFN-γ/IL-2 secretion and proliferation rarely seen in chronic infection. To investigate the timing of loss of HIV-specific T-cell function, we screened cells from 59 treatment-naïve HIV-infected individuals with known dates of infection for proteome-wide responses secreting IFN-γ/IL-2 and IFN-γ alone by ELISPOT. HIV peptide-specific proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution. The contribution of IFN-γ/IL-2 and IFN-γ-only secretion to the total HIV-specific response was compared in subjects infected <6, 6–12, and 12–36 mo earlier. The frequency of IFN-γ/IL-2-secreting cells fell, while that of IFN-γ-only secretion rose with time from infection. HIV peptide-specific proliferative responses were almost exclusively mediated by CD8+ T cells, and were significantly lower in cells obtained from the 12–36 mo versus < 6 mo post-infection groups. By the second year of infection there was a significant difference in these functions compared to those assessed within 6 mo.
doi:10.1089/vim.2009.0084
PMCID: PMC2942873  PMID: 20373996
5.  Performance of an Agar Dilution Method and a Vitek 2 Card for Detection of Inducible Clindamycin Resistance in Staphylococcus spp.▿  
Journal of Clinical Microbiology  2010;48(4):1354-1357.
The D-zone test detects inducible clindamycin resistance in Staphylococcus spp. Two other methods not described by the Clinical and Laboratory Standards Institute (CLSI) are available to test for this resistance mechanism: an agar dilution method and new Vitek 2 cards. This study evaluated the performance of both methods in detecting inducible clindamycin resistance. Nonduplicate clinical strains of Staphylococcus spp. (111 Staphylococcus aureus and 52 coagulase-negative staphylococcus strains), intermediate or resistant to erythromycin but susceptible to clindamycin, were obtained from three hospitals in Montreal, Quebec, Canada. Molecular analysis to detect resistance genes was conducted on all strains. A Mueller-Hinton agar containing 1 mg of erythromycin and 0.5 mg of clindamycin/liter was used for the dilution method, and two inocula were tested: 104 and 105 CFU per spot. Plates were read at 24 and 48 h. The Vitek 2 AST-P580 card was used according to the manufacturer's recommendations. The results were compared to those of the D-zone test. The D-zone test was positive in 134 of 163 (82%) strains. With the 104 CFU inoculum, the sensitivities were 84 and 99% at 24 and 48 h, respectively. The 105 CFU inoculum increased the sensitivities at 24 and 48 h to 91 and 100%, respectively. The specificity was 100% for the 104 CFU inoculum at 24 h and 97% for the other combinations. The sensitivity and specificity for the Vitek 2 card were 93 and 100%, respectively. The performance of both the agar dilution method and the Vitek 2 card was good, but these methods were not as sensitive as the D-zone test at 24 h.
doi:10.1128/JCM.01751-09
PMCID: PMC2849538  PMID: 20164285
6.  Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals 
Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.
PMCID: PMC2533563  PMID: 18923731
Antiretrovirals; Coinfection; Hepatitis C virus; HIV; Practical guide
7.  Confirmatory Real-Time PCR Assay for Human Papillomavirus (HPV) Type 52 Infection in Anogenital Specimens Screened for HPV Infection with the Linear Array HPV Genotyping Test▿  
Journal of Clinical Microbiology  2007;45(11):3821-3823.
A novel real-time PCR assay for detection of human papillomavirus type 52 (HPV-52) DNA (RT-52) was evaluated on 265 anogenital samples. RT-52 had a sensitivity of 98.4% and a specificity of 100% compared to conventional HPV-52 typing assays, including hybridization of PGMY products with an HPV-52-specific probe and PCR sequencing of HPV-52 E6.
doi:10.1128/JCM.01145-07
PMCID: PMC2168527  PMID: 17898159
8.  Enhanced Detection and Typing of Human Papillomavirus (HPV) DNA in Anogenital Samples with PGMY Primers and the Linear Array HPV Genotyping Test 
Journal of Clinical Microbiology  2006;44(6):1998-2006.
The Roche PGMY primer-based research prototype line blot assay (PGMY-LB) is a convenient tool in epidemiological studies for the detection and typing of human papillomavirus (HPV) DNA. This assay has been optimized and is being commercialized as the Linear Array HPV genotyping test (LA-HPV). We assessed the agreement between LA-HPV and PGMY-LB for detection and typing of 37 HPV genotypes in 528 anogenital samples (236 anal, 146 physician-collected cervical, and 146 self-collected cervicovaginal swabs) obtained from human immunodeficiency virus-seropositive individuals (236 men and 146 women). HPV DNA was detected in 433 (82.0%) and 458 (86.7%) samples with PGMY-LB and LA-HPV (P = 0.047), respectively, for an excellent agreement of 93.8% (kappa = 0.76). Of the 17,094 HPV typing results, 16,562 (1,743 positive and 14,819 negative results) were concordant between tests (agreement = 96.9%; kappa = 0.76). The mean agreement between tests for each type was 96.4% ± 2.4% (95% confidence interval [CI], 95.6% to 97.2%; range, 86% to 100%), for an excellent mean kappa value of 0.85 ± 0.10 (95% CI, 0.82 to 0.87). However, detection rates for most HPV types were greater with LA-HPV. The mean number of types per sample detected by LA-HPV (4.2 ± 3.4; 95% CI, 3.9 to 4.5; median, 3.0) was greater than that for PGMY-LB (3.4 ± 3.0; 95% CI, 3.1 to 3.6; median, 2.0) (P < 0.001). The number of types detected in excess by LA-HPV in anal samples correlated with the number of types per sample (r = 0.49 ± 0.06; P = 0.001) but not with patient age (r = 0.03 ± 0.06; P = 0.57), CD4 cell counts (r = 0.06 ± 0.06; P = 0.13), or the grade of anal disease (r = −0.11 ± 0.06; P = 0.07). LA-HPV compared favorably with PGMY-LB but yielded higher detection rates for newer and well-known HPV types.
doi:10.1128/JCM.00104-06
PMCID: PMC1489445  PMID: 16757590
9.  HIV-associated lipodystrophy syndrome: A review of clinical aspects 
Approximately two years after the introduction of highly active antiretroviral therapy for the treatment of HIV infection, body shape changes and metabolic abnormalities were increasingly observed. Initially, these were ascribed to protease inhibitors, but it is now clear that nucleoside reverse transcriptase inhibitors also contribute to lipodystrophy syndrome. The syndrome groups together clinical conditions describing changes in body fat distribution that include lipoatrophy, lipoaccumulation or both. However, there does not appear to be a direct link between lipoatrophy and lipoaccumulation that would support a single mechanism for the redistribution of body fat. Currently, there is no clear definition of lipodystrophy, which explains the difficulty in determining its prevalence and etiology. There are no current guidelines for the treatment of fat distribution abnormalities that occur in the absence of other metabolic complications. The present article reviews the current state of knowledge of the definition, symptoms, risk factors, pathogenesis, diagnosis and treatment of the morphological changes associated with lipodystrophy syndrome.
PMCID: PMC2095035  PMID: 18159551
Adverse events; Antiretroviral drugs; Fat accumulation; HIV infection; Lipoatrophy; Lipodystrophy; Metabolic complications
10.  Cerebral Mycobacterium avium abscesses: Late immune reconstitution syndrome in an HIV-1-infected patient receiving highly active antiretroviral therapy 
A patient who developed an atypical manifestation of Mycobacterium avium complex (MAC) infection almost two years after starting effective highly active antiretroviral therapy is described. The recurrence, manifested as brain abscesses in the central nervous system, was an uncommon form of MAC disease usually reported postmortem. An increased CD4 cell count, localized and suppurative infection, and the absence of systemic evidence of infection were consistent with a late immune reconstitution syndrome. The present case report adds to the understanding of MAC disease in HIV-infected patients.
PMCID: PMC2095025  PMID: 18159542
Central nervous system infections; Immune reconstitution syndrome; Mycobacterium avium complex
11.  The laboratory diagnosis of genital human papillomavirus infections 
Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.
PMCID: PMC2095016  PMID: 18159534
Cancer; HPV; PCR; Screening; STI
12.  Is there anything left to learn? A report on the Fifth International Workshop on HIV Drug Resistance 
Although insight into the viral dynamics of human immunodeficiency virus (HIV) infection has increased dramatically over the past year, there remains much to learn in the field of antiretroviral drug resistance. Transmission of isolates with primary drug resistance is increasingly recognized. With respect to reverse transcriptase inhibitors, it appears that the use of drugs in combination may forestall the development of resistance once therapy has been initiated. Further, certain findings, particularly with respect to zidovudine and lamivudine, suggest that emergence of resistance to one agent may lead to increased susceptibility to another. These data may allow evaluation of innovative treatment strategies to avoid the development of multidrug resistance, which has now been reported in a number of settings. Protease inhibitors (PIs) are, on an individual basis, the most potent antiretroviral compounds available today. A number of studies have shown that resistance to these agents develops after the accumulation of several mutations in the protease gene of HIV. As with reverse transcriptase inhibitors, the use of PIs in the context of regimens designed to suppress viral replication as much as possible appears to forestall, perhaps indefinitely, the development of drug resistance. Although different patterns of resistance mutations have been described for the different PIs available, the issue of cross-resistance remains unresolved. For the time being, it may be best to consider all PIs as a single agent that must always be used in a regimen designed to maximally suppress viral load. In conclusion, research in the field of antiretroviral drug resistance has never been more active and productive. It is hoped that such research will lead to the development of an integrated model of the clinical and laboratory management of HIV-infected individuals.
PMCID: PMC3250909  PMID: 22346539
Antiretroviral therapy; Drug resistance; Human immunodeficiency virus

Results 1-12 (12)