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The authors of a systematic review and meta-analysis conclude that the benefit of convalescent plasma (CP) in the treatment of COVID-19 is limited. Among other systematic reviews, only one found an indication of benefit of CP. However, a meta-analysis needs a focused and meaningful clinical question and should include studies which are designed to test a reasonable hypothesis. Clinical trials to support the licensing of medicines should aim to define as exactly as possible the investigational drug and target disease. In the case of COVID-19, trial details (e.g., duration, stage and severity of disease, and antibody content and dose of CP) are quite heterogeneous. The so far available evidence suggests that the hypothesis should be sharpened as to treat COVID -19 patients at risk for developing severe disease as early enough with a sufficiently high dose of specific antibodies. It has been demonstrated that such an approach is feasible, and the lack of an independent reproduction by further trials with a really comparable design can probably not be compensated by compiling all available, heterogenous trials, even with the best methodology of a systematic review and meta-analysis. Though the COVID-19 pandemic appears to be fading, we should not neglect the search for effective prevention and treatments, given the still high death toll of COVID-19. Monoclonal antibodies were found effective in the early phase of the pandemic; however, due to new variants of SARS-COV2 undermining their efficacy they are no longer recommended by the current NIH guidelines. CP can provide a spectrum of polyclonal antibodies in close timely and regional connection to the particular prevalent virus variant. It would be extremely valuable to obtain a solid scientific foundation for the principle of target specific and temporarily adapted passive immunization, which could be a fast and flexible instrument also in future outbreaks of novel pathogens.

The complex COVID-19-associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2-macroglobulin (α2-M) levels from severe COVID-19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone- and protease-coated web-like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and “versatile” inhibitor α2-M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2-M in COVID-19.

We are overwhelmed by scientific publications on clinical observations, virology and epidemiology of SARS-CoV-2 infections. There is a growing body of evidence that hypercoagulability complicates COVID-19, probably contributing to poor prognosis.

The complex COVID‐19‐associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2‐macroglobulin (α2‐M) levels from severe COVID‐19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone‐ and protease‐coated web‐like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and “versatile” inhibitor α2‐M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2‐M in COVID‐19.

We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case.

HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered.

Some alphaviruses and flaviviruses, such as the transfusion-relevant Chikungunya and West-Nile virus, are transmitted by mosquitoes. Such viruses are called arboviruses. Bacteria typically transmitted by ticks include Coxiella burnetii [1], Borrelia, Ehrlichia, and Anaplasma. These are referred to as arbobacteria [2]. Protozoae include plasmodia which are transmitted via mosquitoes, leishmania transmitted via sand flies (Phlebotomus), and for example trypanosoma transmitted via kissing bugs (Triatoma). The latter are grouped under the name arboprotozoa [3]. The following nematodes are transmitted by arthropods as vectors to humans: microfilaria of Wuchereria bancrofti via mosquitoes (Culex), Onchocera (Onchocera volvulus in Africa, O. caecutiens in South America) via black fly (Simulium) and Loa loa (African eye worm) via horse flies (Tabanidae) – therefore these agents are here grouped under the name arbonematodes.

Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles.

Antiretroviral drug resistance is mostly linked to a complex interaction of several amino acids with variable importance or a single amino acid. To facilitate the interpretation of observed mutation patterns, hospital university centers have developed several interpretation systems. All the currently available interpretation algorithms evolved, are being continuously updated and have been improved during the last decade. Some discrepancies are still evident that are partially smoothened by link of the individual programs with other systems. After the interpretation of HIV-1 group M subtype B mutations, a refined algorithm for the other group M subtypes was developed followed by the interpretation of HIV-1 group O and HIV-2 mutations. The process of improvement is ongoing, due to the better understanding and interpretation of single and cluster mutations and the availability of new antiretroviral substances. The knowledge gained from the experience of HIV drug resistance testing has been used to establish the interpretation of HBV polymerase mutations and will be extended for the treatment of HCV infected with protease inhibitors.

We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of adaptation to humans.

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.

Mit der Umsetzung der EU-Richtlinien 2004/23/EG und 2006/17/EG im Gewebegesetz sowie den begleitenden Verordnungen (Arzneimittel- und Wirkstoffherstellungsverordnung, Transplantationsgesetz-Gewebeverordnung) wurden die grundlegenden Anforderungen an die Virussicherheit der Gewebespenden allgemein definiert. Wahrend infektionsserologische Testungen (Anti-HIV 1/2, Anti-HCV, Hepatitis-B-Oberflachenantigen, Anti-Hepatitis-B-Core-Antigen, Treponema-pallidum-Hamagglutinationsassay) vorgeschrieben sind, wird der Nukleinsaure-Nachweis fur HIV, HBV und HCV nicht explizit gefordert. Anhand in der Literatur berichteter Virusubertragungen, gewebespezifischer Besonderheiten sowie Herstellungs- und gegebenenfalls Inaktivierungsverfahren wird eine Bewertung des Stellenwertes des HIV/HCV/HBV-Nachweises mittels Nukleinsaure-Amplifikationstechniken (NAT) bei Spendern unterschiedlicher Gewebe vorgenommen und mit den Erfahrungen des Blutspendewesens verglichen. Muskuloskelettale Gewebe besitzen infolge des zumeist hohen Blutgehalts der Gewebe, des umfangreichen Entnahmespektrums, der bisher beschriebenen Ubertragungen, der unterschiedlichen Herstellungsverfahren sowie der hohen Spender-Empfanger-Ratio ein signifikantes Risiko, HIV/HCV/HBV zu ubertragen. Daher sollte bei Spendern muskuloskelettaler Gewebe, die keinem effektiven Virusinaktivierungsverfahren unterzogen werden, eine HIV-, HBV- und HCV-NAT-Testung erfolgen. Kardiovaskulares Gewebe hat bei Durchfuhrung der serologischen Testung ein sehr geringes Restrisiko der HIV/HCV/HBV-Ubertragung. Aufgrund der fehlenden Moglichkeit einer effektiven Virusinaktivierung (Erhalt der Gewebemorphologie) und der Spender-Empfanger-Ratio von bis zu 1:10 sollte die HIV-, HCV- und HBV-NAT jedoch als zusatzliche Sicherheitsmasnahme erfolgen. Augenhornhaute besitzen aus physiologisch-morphologischer sowie epidemiologischer Sicht das geringste HIV/HCV/HBV-Ubertragungsrisiko, jedoch sollte die HCV-NAT durchgefuhrt werden. Eine Quarantanelagerung der Gewebe eines Spenders kann bei negativem Ergebnis der HIV/HCV/HBV-NAT grundsatzlich entfallen. Aufgrund der vielfaltigen Synergieeffekte mit der Transfusionsmedizin bietet es sich fur Gewebebanken an, die Testung der infektionsserologischen bzw. molekularbiologischen Laborparameter in Kooperation mit Blutspendediensten durchzufuhren.

Anaplasma phagocytophilum, marginatum; Bartonella henselae; Borrelia burgdorferi, afzelii, garinii; Coxiella burnetii; Ehrlichia chaffeensis; Francisella tularensis; Rickettsia prowazekii, akari, rickettsii andYersinia pestis are also known as arbobacteria. Diseases caused by these bacteria are basically zoonoses, i.e. diseases transmittable from animals to humans, and have been known as such for about 100 years (table ​(table1).1). A part of the individual pathogens have not been described until the past few decades. Based on molecular biology analyses, R. prowazekii, Ehrlichia and Anaplasma are categorised as Rickettsiales, while Bartonella is categorised as alpha-2-proteobacteria, Coxiella, Rickettsia grylli and F. tularensis as gamma proteobacteria, and Y. pestis as enterobacteria [1]. Table 1 Vectors for arbobacteria Most arbobacteria grow predominantly intracellularly. However, Borrelia bacteria grow intracellularly and extracellularly, and Yersinia mainly extracellularly. The above described arbobacteria, when transmitted by ticks, show seasonal occurrence and a partly changed antigen repertoire in vector and mammal. R. prowazekii is transmitted by lice world-wide throughout the year. The major clinical symptoms such infections have in common include fever, exanthema, headache, and lymph node swelling, partly a pronounced erythema at the site of the sting, and encephalitic disorders. Neutropenia and thrombocytopenia can occur later. Treatment: Doxycycline is the treatment of choice against most of these bacteria, followed by chloramphenicol and cephalosporins. Quinolones are ineffective against R. prowazekii. The treatment of choice against Y. pestis and F. tularensis is streptomycin or gentamycin, and in addition doxycycline or ciprofloxacine. C. burnetii has been dealt with separately [2]. Therefore, this pathogen is not included in the present review, neither are rare tropical and/or pure tropical diseases. The oriental flea (Xenopsylla cheopsis) is considered as the most effective transmitter for Y. pestis. More than 30 other flea species are known which can transmit Y. pestis as intermediary hosts, including Pulex irritans (human flea), which can play a role in human-to-human transmission. The human louse can also be a vector for transmission of Y. pestis [3]. The following section provides for each pathogen information on the general state of knowledge, characteristics of the pathogen, infectious disease, epidemiology, methods of detection and occurrence of the pathogen in the donor population. This is followed by information concerning all pathogens on epidemiology, defence situation, treatment and prevention in recipient populations as well as a summary evaluation.

Clinical observations indicate that human immunodeficiency virus (HIV)‐positive women experience more postoperative problems than do HIV-negative women. To obtain a better estimate of the individual risk of postoperative morbidity among HIV-infected women, and to determine which procedures pose the greatest risk, we performed a retrospective case-control study in which we assessed the outcomes after 235 obstetric and gynecologic surgical procedures. For purposes of comparison, an HIV-negative control patient was matched for each of the 235 surgical procedures performed, on the basis of the type of procedure and patient age. We found a significantly greater number of postoperative complications among the HIV-positive women. Higher complication rates occurred after abdominal surgery (odds ratio [OR], 3.6; ) and curettage (OR, 7.7; P p .001 ). Among HIV-infected women, the risk of complications was associated with immune status. AntiP p .06 retroviral therapy and standard perioperative antibiotic prophylaxis did not decrease the risk of complications. Indications for performing abdominal surgery and curettage on HIV-infected women should be carefully weighed against the potential risk of postoperative complications.

1IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cite, F-75018 Paris, France 2IAME, UMR 1137, INSERM, F-75018 Paris, France 3AP-HP, Hopital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France 4Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium 5Universite catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium 6Max von Pettenkofer Institute, Ludwig Maximilian University Munich, Munich, Germany 7Max Planck Institute for Informatics, Saarbrucken, Germany 8Johann Wolfgang Goethe-University Hospital, Institute for Medical Virology, German National Reference Centre for Retroviruses, Frankfurt, Germany 9Institute of Virology, University of Cologne, Germany 10Medizinisches Labor Dr. Berg, Berlin, Germany

To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.

Hemophilia defines a group of hereditary bleeding disorders: hemophilia A (deficiency of Factor VIII, FVIII), hemophilia B (deficiency of FIX), and para-hemophilia (deficiency of FV). These result from mutations in clotting factor genes. As in the large majority of bleeding disorders ([Table 1][1

Genotypes of samples from protease inhibitor-naïve patients in Frankfurt's HIV Cohort were analyzed with five tipranavir resistance prediction algorithms. Mean scores were higher in non-B than in B subtypes. The proportion of non-B subtypes increased with increasing scores, except in weighted algorithms. Virtual and in vitro phenotype analyses of samples with increased scores showed no reduced tipranavir susceptibility. Current algorithms appear suboptimal for interpretation of resistance to tipranavir in non-B subtypes; increased scores might reflect algorithm bias rather than “natural resistance.”

Objective Replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome. For RT inhibitors, almost all identified mutations are located within the polymerase; therefore, general genotyping confines to investigate this subunit. Recently several studies have shown that substitutions within the RNase H and the connection domain increase antiviral drug-resistance in vitro, and some of them are present in patient isolates. Aim The aim of the present study was to investigate the prevalence of these substitutions and their association with mutations in the polymerase domain arising during antiretroviral treatment. Materials and methods We performed genotypic analyzes on seventy-four virus isolates derived from treated and untreated patients, followed at the HIV Centre of the Johann Wolfgang Goethe University Hospital (Frankfurt/Main, Germany). We subsequently analysed the different substitutions in the c-terminal region to evaluate whether there were associations with each other, n-terminal substitutions or with antiretroviral treatment. Results We identified several primer grip substitutions, but almost all of them were located in the connection domain. This is consistent with other in-vivo studies, in which especially the primer grip residues located in the RNase H were unvaried. Furthermore, we identified other substitutions in the connection domain and in the RNase H. Especially E399D seemed to be associated with an antiretroviral treatment and N-terminal resistance-delivering mutations. Conclusion Some of the identified substitutions were associated with antiviral treatment and drug resistance-associated mutations. Due to the low prevalence of C-terminal mutations and as only a few of them could be associated with antiviral treatment and N-terminal resistance-delivering mutations, we would not recommend routinely testing of the C-terminal RT region.

I have several criticisms relating to the published box. No mention is made of its source. In the United States, West Nile virus occurs to an epidemiologically relevant degree in birds and humans; transmission to humans in Germany has not occurred thus far, according to all reports that are currently available. Further investigations in the Robert Koch-Institute have not provided any indication of the prevalence of this flavivirus in humans in Germany either. LCMV refers to the lymphochoriomeningitis virus, not the lymphocytic choriomeningitis virus, This arenavirus occurs in rodents in the US, especially in mice. In Germany, no infection has thus far occurred, even in children. SARS is the “severe acute respiratory syndrome” coronavirus, which was epidemiologically highly relevant in 2002 and 2003. A less pathogenic similar coronavirus caused a second small epidemic in China in 2004; since then, this zoonotic coronavirus has remained irrelevant for central Europe and the US. Pneumocystis is clinically important after transplantation. However, since 2004/05, this fungus, which occurs in human beings, has been renamed Pneumocystis jirovecii and not Pneumocystis carinii. An article that was published in 2009 should have included current terminology and meanings..

In der Originalpublikation dieses Beitrags wurden die Autoren leider nicht innerhalb der Metadaten aufgefuhrt. Die Liste der Autoren lautet wie folgt: Holger F. Rabenau, Norbert Bannert, Annemarie Berger, Oliver Donoso Mantke, Josef Eberle, Martin Enders, Helmut Fickenscher, Hans-Peter Grunert, Lutz Gurtler, Albert Heim, Daniela Huzly, Rolf Kaiser, Klaus Korn, Sigrid Nick, Claudia Kucherer, Micha Nubling, Martin Obermeier, Marcus Panning, Heinz Zeichhardt.

In this report, we describe the construction and characterization of the first full-length infectious molecular clone from the Cameroonian HIV-1 group O primary isolate MVP8913. Virus obtained after transfection of the proviral clone pCMO2.3 replicated to levels comparable to its parental isolate in the human T-cell line PM-1, although replication was reduced by fivefold in peripheral blood mononuclear cells (PBMC) and was barely detectable in primary monocyte-derived macrophages (MDM). Phylogenetic analysis of the complete proviral sequence revealed a closer relationship to ANT70 than to MVP5180, the two prototypic group O primary isolates. All reading frames for structural and accessory genes were open except for vpr that contained an in-frame stop codon. In the nef gene, a mutation disrupting the functionally important myristoylation signal was observed. Repairing the defect in nef enhanced replication in PBMC and MDM, although repairing the vpr defect only affected replication in MDM, consistent with the known phenotypes of vpr and nef mutants in HIV-1 group M viruses. Repairing both vpr and nef showed an additive effect, but the resulting virus was still impaired compared to the parental isolate. This defect was overcome when the gag-pol coding region was exchanged for that from another O-type isolate giving rise to the proviral clone pCMO2.5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses.

We tested dried blood from an ABO bedside test card which had been stored at room temperature for 12 years, to prove that a patient with HIV-1 infection had been infected by blood transfusion.Immunoblots for HIV-1 antibodies and threefold PCRs with half-nested primers for the HIV-1 integrase gene were done with eluates from the dried blood spots.HIV-1 antibodies and HIV-1 DNA could be detected in the sample from one unit of blood, but not from the two other units or from the recipient before transfusion.Further studies should be done on the validity of stored dried blood as an alternative to the storage of frozen donor serum for several years for 'look-back' studies.

After incubation of H9 cells infected with human immunodeficiency virus (HIV) with pepstatin A at 10 −4 M for 2, 4, or 11 days, the culture medium contained significantly less HIV core antigen (p24) than controls without pepstatin A and no or only borderline activity of reverse transcriptase was detected. In addition, after pepstatin A treatment no infectious HIV at 2 or 4 days and only minimal amounts at 11 days were detectable in the culture medium.