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  • HIV Infections
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  • 1
    In: Sexually Transmitted Diseases, 2010, Vol.37(7), pp.454-459
    Description: BACKGROUND:: The objective of this study was to assess the seroprevalence of coinfecting viruses and Treponema pallidum (T. pallidum) in a cohort of 205 antiretrovirally treated HIV-infected individuals (152 females and 53 males, aged: 19–71 years) in rural Lesotho. Furthermore agent-specific immune responses were investigated by analyzing antibody titers against herpes simplex virus type 2 (HSV-2) and against T. pallidum. METHODS:: Serum samples were tested by enzyme-linked immunosorbent assay for antibodies against HSV-2, cytomegalovirus, hepatitis A, B, and C viruses, and T. pallidum. RESULTS:: Seroprevalences (95% confidence intervals) were found to be 100% (98.5%–100%) for anti-cytomegalovirus, 98.5% (95.7%–99.7%) for anti-hepatitis A virus, 35.5% (28.9%–42.6%) for anti-HBc, 5.5% (2.8%–9.6%) for hepatitis B surface antigen, and 0.5% (0.0%–2.8%) for anti-hepatitis C virus. Only 78.5% (72.2%–84.0%) were anti-HSV-2 positive and 29.0% (22.8%–35.8%) had antibodies against T. pallidum. Only anti-HSV-2 titers showed gender- and CD4 cell-count dependent differences: females with 〉500 CD4 cells/μL had an average anti-HSV-2 titer of 446 compared with males of 398 AU/mL (not significant), but in those with 250 to 500 CD4 cells/μL, there was a significant difference with a mean titer of 467 compared to 302 AU/mL in males (P = 0.001). CONCLUSIONS:: A high seroprevalence of CMV, HAV, and HBV was found in both genders. One-third of the patients had been exposed to HBV and T. pallidum. The generally high HSV-2 prevalence showed gender- and CD4 cell count-dependent differences in HSV-2 antibody titer.
    Keywords: Hiv Infections -- Research ; Hiv Infections -- Demographic Aspects ; Immune Response -- Research ; Immune Response -- Demographic Aspects ; Treponema Pallidum -- Drug Therapy ; Enzyme-linked Immunosorbent Assay -- Usage;
    ISSN: 0148-5717
    E-ISSN: 15374521
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  • 2
    Language: English
    In: Medical Microbiology and Immunology, 2016, Vol.205(4), pp.315-320
    Description: Mutations in the genome of HIV-1 can compromise the success of antiretroviral treatments (ARTs) in HIV-1-infected individuals. The Frankfurt HIV Cohort Study Resistance Database (FHCS-RD) has previously documented a decline in the burden of resistance-associated mutations (RAMs) following the implementation of several new antiretroviral therapy regimens in 2007. In the current study, the annual burden of RAMs documented in the FHCS-RD in 2005–2013 was set in relation to the annual number of all cohort patients, drug regimens, available resistance tests, and prevalence for each RAM on relevant codons of reverse transcriptase (RT) and protease (PR) genes. A specific focus was put on the prevalence of the tenofovir disoproxil fumarate (TDF) signature mutation K65R in HIV-1 RT in relation to the application of TDF within ART. Between 2005 and 2012, a total of 4423 HIV genotyping data sets from 4509 patients were analysed. All mutations show a consistent decline, and the most impressive decrease was observed for thymidine analogue mutations (TAMs). The frequency of non-TAMs and PR mutations also decreased, but generally to a lower extent. The prevalence of K65R decreased from 2.6 % in 2005 to 0.2 % in 2012 despite increased use of TDF-containing ART. Both the improved strategic use of TDF in ARTs and generally more effective ART regimens may have resulted in decreasing RAM prevalences in FHCS-RD since 2007. These trends challenge the cost-effectiveness of resistance testing prior to failing ART.
    Keywords: Frankfurt HIV Cohort Study ; Tenofovir disoproxil fumarate ; RAM ; Prevalence ; K65R
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 3
    Language: English
    In: Scandinavian Journal of Infectious Diseases, 01 September 2014, Vol.46(9), pp.656-659
    Description: The immune response after influenza vaccination is impaired in HIV-infected individuals and can be enhanced by a second dose. The durability of the antibody protection and its clinical benefit is not known. We investigated clinical symptoms...
    Keywords: HIV ; H1n1 ; Adjuvanted ; Pandemic ; Durability ; Medicine
    ISSN: 0036-5548
    E-ISSN: 1651-1980
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  • 4
    Language: English
    In: The Journal of infectious diseases, 15 October 2002, Vol.186(8), pp.1086-91
    Description: This study evaluated 1433 human immunodeficiency virus (HIV)-infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of 〈400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22-3.84; P〈.0001) and a decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of 〈400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients (P〈.0001), but the difference between the groups persisted into the third year of follow-up (P=.0007). Even patients who had experienced 〈2 months of nucleoside therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P=.009). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to confer a disadvantage, in terms of risk of virus rebound, that persists for several years.
    Keywords: Antiretroviral Therapy, Highly Active ; Anti-HIV Agents -- Administration & Dosage ; HIV -- Drug Effects ; HIV Infections -- Drug Therapy
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 5
    Language: English
    In: Expert Review of Molecular Diagnostics, 01 May 2007, Vol.7(3), pp.237-246
    Description: Infection with HIV results in lifelong persistence of the virus in the body of infected persons, independent of antiretroviral treatment. Therefore, efficient and meaningful therapy monitoring has been developed since its introduction in the 1980s. Whereas, primarily, the measurement of the CD4 cell count was the most important clinical marker of disease progression, nowadays the estimation of plasma viral load with molecular methods plays a major role as a marker of therapy success. To optimize therapy changes in patients failing on antiretroviral therapy regimen, HIV-1 genotyping has been introduced and is now widely accepted as an additional diagnostic tool. Due to this increase in diagnostic parameters, clinicians and virologists have to cope with many different methods. This review should give a brief overview of the current commercially available assays for detection and quantification of HIV, as well as for HIV-1 genotypic resistance testing. Quantitative reverse transcriptase PCR, real-time PCR, nucleic acid sequence-based amplification and the branched DNA system are described in detail, and the advantages and disadvantages are discussed. In addition, two commercially available HIV-1 genotyping assays are compared. However, a general recommendation to favor one system over the other cannot be given, because the final decision of which system to use should be decided on the individual requirements.
    Keywords: Bdna ; HIV-1 Genotyping ; HIV-1 Monitoring ; Nasba ; Real-Time Pcr ; Rt-Pcr ; Viral Load ; Medicine
    ISSN: 1473-7159
    E-ISSN: 1744-8352
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  • 6
    Language: English
    In: Clinical chemistry, July 2006, Vol.52(7), pp.1258-66
    Description: Current HIV-1 viral-load assays are too expensive for resource-limited settings. In some countries, monitoring of antiretroviral therapy is now more expensive than treatment itself. In addition, some commercial assays have shown shortcomings in quantifying rare genotypes. We evaluated real-time reverse transcription-PCR with internal control targeting the conserved long terminal repeat (LTR) domain of HIV-1 on reference panels and patient samples from Brazil (n = 1186), South Africa (n = 130), India (n = 44), and Germany (n = 127). The detection limit was 31.9 IU of HIV-1 RNA/mL of plasma (〉 95% probability of detection, Probit analysis). The internal control showed inhibition in 3.7% of samples (95% confidence interval, 2.32%-5.9%; n = 454; 40 different runs). Comparative qualitative testing yielded the following: Roche Amplicor vs LTR assay (n = 431 samples), 51.7% vs 65% positives; Amplicor Ultrasensitive vs LTR (n = 133), 81.2% vs 82.7%; BioMerieux NucliSens HIV-1 QT (n = 453), 60.5% vs 65.1%; Bayer Versant 3.0 (n = 433), 57.7% vs 55.4%; total (n = 1450), 59.0% vs 63.8% positives. Intra-/interassay variability at medium and near-negative concentrations was 18%-51%. The quantification range was 50-10,000,000 IU/mL. Viral loads for subtypes A-D, F-J, AE, and AG yielded mean differences of 0.31 log(10) compared with Amplicor in the 10(3)-10(4) IU/mL range. HIV-1 N and O were not detected by Amplicor, but yielded up to 180 180.00 IU/mL in the LTR assay. Viral loads in stored samples from all countries, compared with Amplicor, NucliSens, or Versant, yielded regression line slopes (SD) of 0.9 (0.13) (P 〈 0.001 for all). This method offers all features of commercial assays and covers all relevant genotypes. It could allow general monitoring of antiretroviral therapy in resource-limited settings.
    Keywords: HIV Long Terminal Repeat ; HIV-1 ; Viral Load ; Reverse Transcriptase Polymerase Chain Reaction -- Methods
    ISSN: 0009-9147
    E-ISSN: 15308561
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  • 7
    In: Journal of Clinical Microbiology, 1998, Vol. 36(8), p.2235
    Description: In order to reduce the diagnostic window between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new screening enzyme-linked immunosorbent assays (ELISAs) which permit the simultaneous detection of HIV antigen and antibody have been developed. Two fourth-generation assays, HIV DUO (Biomérieux) and HIV Combi (Boehringer Mannheim), for the combined detection of HIV antigen and antibody, were compared with a third-generation assay (HIV-1/HIV-2 3rd Generation Plus enzyme immunoassay [EIA]; Abbott) and a p24 antigen test (HIV-1 Ag monoclonal; Abbott). A total of 17 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 255 potentially cross-reactive serum samples were tested. Ten seroconversions were detected an average of 8.1 days earlier with HIV DUO and 7.5 days earlier with HIV Combi than with the third-generation ELISA. Overall, in the 17 seroconversion panels tested, HIV DUO detected HIV-1 infection an average of 4.8 days and HIV Combi detected infection an average of 4.4 days earlier than HIV-1/HIV-2 3rd Generation Plus EIA. HIV antigen was detected with HIV DUO and HIV Combi in all of the 15 cell culture supernatants infected with different HIV-1 subtypes, including subtype O. With fourth-generation assays, considerably fewer false-positive results (n = 4 to 6) were obtained, in comparison with the third-generation EIA (n = 18). Fourth-generation assays permit an earlier diagnosis of HIV infection than third-generation antibody screening assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion.
    Keywords: AIDS Serodiagnosis ; Enzyme-Linked Immunosorbent Assay -- Methods ; HIV Antibodies -- Blood ; HIV Core Protein P24 -- Blood ; HIV Infections -- Diagnosis;
    ISSN: 0095-1137
    ISSN: 00951137
    E-ISSN: 1098660X
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  • 8
    Language: English
    In: Medical Microbiology and Immunology, 2009, Vol.198(3), pp.147-155
    Description: The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered.
    Keywords: HIV ; HBV ; HCV ; Diagnostics ; Therapy
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 9
    Language: English
    In: Antimicrobial agents and chemotherapy, September 2007, Vol.51(9), pp.3264-72
    Description: The objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, to be addressed for improved personalized therapy. The presence of human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count at week 48, infections and side effects during 48 weeks, indicators of liver toxicity and lipid abnormalities at week 48, and a 12-h saquinavir plasma concentration-versus-time profile were assessed in 56 patients receiving saquinavir-ritonavir (1,000 and 100 mg, respectively) twice daily (44 therapy-naïve and 12 antiretrovirally pretreated patients) for association with saquinavir plasma concentrations, demographics, baseline values of target parameters, and coadministered antiretrovirals. Antiretroviral failure was observed in 8 of the 56 patients in whom HIV-1 RNA was detectable at week 48. This therapeutic failure was not associated with individual saquinavir pharmacokinetics. More likely, therapeutic failure was related to incidences interfering with antiretroviral therapy, causing therapy interruptions or incompliance. Weak associations were, however, seen between high maximum saquinavir plasma concentrations and both CD4 counts of 〉 or =200 cells microl(-1) at week 48 (P = 0.014) and constitutional side effects during 48 weeks (P = 0.002). However, patients with high CD4 counts and constitutional side effects were not identical (P = 0.53). Saquinavir therapeutic drug monitoring in patients infected with protease inhibitor-susceptible HIV-1 taking saquinavir-ritonavir (1,000 and 100 mg, respectively) is not demanded for improving the antiretroviral effect. It may be contemplated in cases with constitutional side effects or low CD4 counts with weak immune responses.
    Keywords: HIV Infections -- Drug Therapy ; HIV Protease Inhibitors -- Adverse Effects ; HIV-1 -- Drug Effects ; Saquinavir -- Adverse Effects
    ISSN: 0066-4804
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 10
    In: AIDS, 2001, Vol.15(18), pp.2379-2384
    Description: 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.
    Keywords: Human Immunodeficiency Virus 1 ; Acquired Immune Deficiency Syndrome ; Antiviral Agents ; Antiretroviral Therapy ; Highly Active Antiretroviral Therapy ; AIDS: Clinical Aspects ; HIV-1 ; Therapy Adherence ; HIV-1 ; Antiretroviral Therapy ; Highly Active Antiretroviral Therapy ; Therapy Adherence;
    ISSN: 0269-9370
    E-ISSN: 14735571
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