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1.  Generation of a Recombinant Gag Virus-Like-Particle Panel for the Evaluation of p24 Antigen Detection by Diagnostic HIV Tests 
PLoS ONE  2014;9(10):e111552.
Background
Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens.
Methods
We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection.
Results
Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection.
Conclusions
The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.
doi:10.1371/journal.pone.0111552
PMCID: PMC4208835  PMID: 25343245
2.  Use of reverse-transcriptase-based HIV-1 viral load assessment to confirm low viral loads in newly diagnosed patients in Switzerland 
Background
Treatment-naïve patients newly diagnosed with HIV occasionally present with low viral RNA of ≤1’000 copies/ml, raising concerns about viral load underestimation. Because falsely low or undetectable viral loads might lead to inadvertent virus transmission or treatment delays, confirmation of such cases by a sequence-independent viral load test is recommended in Switzerland.
Methods
HIV-1 RNA ≤1’000 cp/ml by Roche’s or Abbott’s tests in patients newly diagnosed from 2010 to 2012 in Switzerland were subjected to viral load testing by the product-enhanced-reverse transcriptase (PERT) assay. These investigations were complemented with repeat and/or alternative viral RNA measurements.
Results
HIV-1 RNA ≤1’000 cp/ml was observed in 71 of 1814 newly diagnosed patients. The PERT assay suggested clinically relevant viral load underestimation in 7 of 32 cases that could be investigated. In four patients, the PERT viral load was 10-1’000-fold higher; this was confirmed by alternative HIV-1 RNA tests. Six of the 7 underestimates had been obtained with meanwhile outdated versions of Roche’s HIV-1 RNA test. In the seventh patient, follow-up revealed similar results for RNA and PERT based viral loads.
Conclusion
PERT assay revealed occasional severe viral load underestimation by versions of HIV-1 RNA tests meanwhile outdated. Underestimation by contemporary tests appears rare, however.
doi:10.1186/1471-2334-14-84
PMCID: PMC3984746  PMID: 24524626
HIV-1; Viral load underestimation; Nucleic acid test; Reverse transcriptase test; PERT assay
3.  Simple Estimation of Incident HIV Infection Rates in Notification Cohorts Based on Window Periods of Algorithms for Evaluation of Line-Immunoassay Result Patterns 
PLoS ONE  2013;8(8):e71662.
Background
Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods.
Methods
We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship ‘Prevalence  =  Incidence x Duration’ in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship ‘incident  =  true incident + false incident’ and also to the IIR derived from the BED incidence assay.
Results
Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R2 = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods.
Conclusions
IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.
doi:10.1371/journal.pone.0071662
PMCID: PMC3753319  PMID: 23990968
5.  Diagnostic performance of line-immunoassay based algorithms for incident HIV-1 infection 
Background
Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications.
Methods
Diagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity.
Results
The 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models.
Conclusions
The method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.
doi:10.1186/1471-2334-12-88
PMCID: PMC3362747  PMID: 22497961
6.  High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease 
BMC Infectious Diseases  2011;11:254.
Background
Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it.
Methods
Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms.
Results
HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients.
Conclusions
The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.
doi:10.1186/1471-2334-11-254
PMCID: PMC3190377  PMID: 21943091
7.  Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells 
Advances in Virology  2011;2011:165871.
An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.
doi:10.1155/2011/165871
PMCID: PMC3265293  PMID: 22312334
8.  Assessment of Recent HIV-1 Infection by a Line Immunoassay for HIV-1/2 Confirmation 
PLoS Medicine  2007;4(12):e343.
Background
Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this “recency” information can also be gained from an HIV confirmatory assay.
Methods and Findings
The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (≤ 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%–46%).
Conclusions
Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.
Jörg Schüpbach and colleagues show that a second-generation Western blot antibody test used to confirm HIV infection can also be used to determine rates of recent HIV infection.
Editors' Summary
Background.
Since the first diagnosed cases of AIDS (acquired immunodeficiency syndrome) in 1981, the AIDS epidemic has spread rapidly. Now, 40 million people are infected with HIV (human immunodeficiency virus), the cause of AIDS. HIV infects and kills immune system cells, leaving infected individuals susceptible to other infectious diseases and tumors. The first, often undiagnosed, stage of HIV infection (primary HIV infection) lasts a few weeks and often involves a flu-like illness. During this stage, the immune system begins to respond to HIV by producing antibodies (proteins that recognize viral molecules called antigens). The time needed for these antibodies to appear on testing “seroconversion” (usually 6–12 weeks) is called the window period of the test; HIV antibody tests done during this period give false negative results. During the second, symptom-free stage of HIV infection, which can last many years, the virus gradually destroys the immune system so that by the third stage of infection unusual infections (for example, persistant yeast infections of the mouth) begin to occur. The fourth stage is characterized by multiple AIDS-indicator conditions such as severe bacterial, fungal, or viral infections, and cancers such as Kaposi sarcoma.
Why Was This Study Done?
To monitor the AIDS/HIV epidemic and HIV prevention programs, it is necessary to know how many people in a population have been recently infected with HIV. Serologic testing algorithms for recent HIV seroconversion (STARHS) provide a way to get this information. Early during seroconversion, low levels of antibodies that bind only weakly to their viral antigens (low-affinity antibodies) are made. Later on, antibody concentrations and tightness of binding increase. STARHS calculate the number of recently infected people by analyzing data from special “detuned” HIV antibody assays (for example, a commercially available test called the BED-EIA) that preferentially detect low-concentration, low-avidity antibodies. This type of test cannot, however, be used to determine whether an individual has an HIV infection, because it will miss a substantial fraction of infected people. Diagnosing HIV in an individual person requires more sensitive tests for antibody detection. In this study, the researchers have investigated whether a test called INNO-LIA, which is already being used in some countries to diagnose HIV infection, can also provide information about the recency (newness) of HIV infections.
What Did the Researchers Do and Find?
Between July 2005 and June 2006, 765 HIV infections were newly diagnosed in Switzerland. Using clinical and laboratory information collected at diagnosis, the researchers classified 195 of these infections as recent infections (occurring within the past year) and 161 as older infections. (The remaining infections could not be classified based on the available medical infomation.) The researchers then compared the ability of INNO-LIA (which measures antibodies to five HIV-1 antigens) and BED-EIA to distinguish recent from older HIV infections. BED-EIA correctly identified as recent 65% of the infections classified as recent based on the clinical information, and identified as older 80% of the infections classified as older based on the clinical information. In other words, this test was 65% sensitive (able to detect 65% of the truly recent infections as defined in this study) and was 80% specific (80% accurate in eliminating non-recent infections.) The two best algorithms (mathematical procedures) for converting INNO-LIA data into estimates of recent HV infections had sensitivities of 50% and 40% and specificities of 95% and 99%, respectively. Using actual test results and taking into account these sensitivities and specificities gave estimates of 35% and 33% for the proportion of the whole study population that had been recently infected. BED-EIA gave an estimate of 37%. Finally, a widely used window-based algorithm for recency estimation that uses the numbers of cases that are defined as recent by BED-EIA and the length of the window period for BED-EIA to calculate the annual number of new infections in populations indicated that 41% of the whole study population had been recently infected.
What Do These Findings Mean?
These findings indicate that numbers of recent HIV infections can be extracted from the INNO-LIA HIV diagnostic test and are comparable to those obtained using a window-based algorithm. The test could, therefore, provide a cost-effective means to improve HIV surveillance in countries like Switzerland that already use it for HIV diagnosis. However, because this approach relies on knowing the sensitivity and specificity of the INNO-LIA algorithms, which may vary between populations, the use of these algorithms to estimate numbers of recent HIV infections must be preceded by an assessment of their sensitivity and specificity in each new setting.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040343.
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including fact sheets on the symptoms of HIV infection, HIV testing, and a chapter on laboratory tests for HIV antibodies
NAM, a UK registered charity, provides information about all aspects of HIV and AIDS, including fact sheets on the stages of HIV infection and HIV testing
The US Centers for Disease Control and Prevention (CDC) provides information on HIV/AIDS, including information on HIV testing and on HIV surveillance by the CDC (in English and Spanish)
Information is available from Avert, an international AIDS charity, on the stages of HIV infection and on HIV testing
Details on the US Centers for Disease Control and Prevention and the World Health Organiztion HIV classification systems are available from the US Department of Veterans Affairs
doi:10.1371/journal.pmed.0040343
PMCID: PMC2100138  PMID: 18052604
9.  Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure 
PLoS ONE  2007;2(1):e173.
Background
Genotypic antiretroviral resistance testing (GRT) in HIV infection with drug resistant virus is recommended to optimize antiretroviral therapy, in particular in patients with virological failure. We estimated the clinical effect, cost and cost-effectiveness of using GRT as compared to expert opinion in patients with antiretroviral treatment failure.
Methods
We developed a mathematical model of HIV disease to describe disease progression in HIV-infected patients with treatment failure and compared the incremental impact of GRT versus expert opinion to guide antiretroviral therapy. The analysis was conducted from the health care (discount rate 4%) and societal (discount rate 2%) perspective. Outcome measures included life-expectancy, quality-adjusted life-expectancy, health care costs, productivity costs and cost-effectiveness in US Dollars per quality-adjusted life-year (QALY) gained. Clinical and economic data were extracted from the large Swiss HIV Cohort Study and clinical trials.
Results
Patients whose treatment was optimized with GRT versus expert opinion had an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and two weeks, respectively. Health care costs with and without GRT were $US 421,000 and $US 419,000, leading to an incremental cost-effectiveness ratio of $US 35,000 per QALY gained. In the analysis from the societal perspective, GRT versus expert opinion led to an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and four weeks, respectively. Health care costs with and without GRT were $US 551,000 and $US 549,000, respectively. When productivity changes were included in the analysis, GRT was cost-saving.
Conclusions
GRT for treatment optimization in HIV-infected patients with treatment failure is a cost-effective use of scarce health care resources and beneficial to the society at large.
doi:10.1371/journal.pone.0000173
PMCID: PMC1769464  PMID: 17245449
10.  Concurrent Infections with Vector-Borne Pathogens Associated with Fatal Hemolytic Anemia in a Cattle Herd in Switzerland 
Journal of Clinical Microbiology  2004;42(8):3775-3780.
Bovine anaplasmosis is a vector-borne disease that results in substantial economic losses in other parts of the world but so far not in northern Europe. In August 2002, a fatal disease outbreak was reported in a large dairy herd in the Swiss canton of Grisons. Diseased animals experienced fever, anorexia, agalactia, and depression. Anemia, ectoparasite infestation, and, occasionally, hemoglobinuria were observed. To determine the roles of vector-borne pathogens and to characterize the disease, blood samples were collected from all 286 animals: 50% of the cows were anemic. Upon microscopic examination of red blood cells, Anaplasma marginale inclusion bodies were found in 47% of the cows. The infection was confirmed serologically and by molecular methods. Interestingly, we also found evidence of infections with Anaplasma phagocytophilum, large Babesia and Theileria spp., and Mycoplasma wenyonii. The last two species had not previously been described in Switzerland. Anemia was significantly associated with the presence of the infectious agents detected, with the exception of A. phagocytophilum. Remarkably, concurrent infections with up to five infectious vector-borne agents were detected in 90% of the ill animals tested by PCR. We concluded that A. marginale was the major cause of the hemolytic anemia, while coinfections with other agents exacerbated the disease. This was the first severe disease outbreak associated with concurrent infections with vector-borne pathogens in alpine Switzerland; it was presumably curtailed by culling of the entire herd. It remains to be seen whether similar disease outbreaks will have to be anticipated in northern Europe in the future.
doi:10.1128/JCM.42.8.3775-3780.2004
PMCID: PMC497630  PMID: 15297529
11.  Direct Evidence for Natural Transmission of Small-Ruminant Lentiviruses of Subtype A4 from Goats to Sheep and Vice Versa 
Journal of Virology  2004;78(14):7518-7522.
Small-ruminant lentiviruses (SRLV), which include the caprine arthritis-encephalitis and the maedi-visna virus, cause persistent inflammatory infections in goats and sheep. SRLV are mainly transmitted from mother to offspring through milk. Transmission after prolonged contact between adult animals has also been observed. The observation that certain SRLV subtypes are found in both goats and sheep suggests that interspecies transmission has occurred on several occasions in the past. We investigated seropositive goats and sheep that were kept together in small mixed herds. Phylogenetic analysis of long proviral sequences in gag and pol, combined with epidemiologic information, demonstrated natural sheep-to-goat transmission of the recently identified SRLV subtype A4 in two instances and goat-to-sheep transmission of the same subtype in one instance. In a further mixed cluster, the direction of the interspecies transmission could not be determined. These findings present for the first time direct evidence that natural interspecies transmission of SRLV is ongoing in both directions. The findings are of relevance to virus eradication programs in both species.
doi:10.1128/JVI.78.14.7518-7522.2004
PMCID: PMC434116  PMID: 15220425
12.  Identification and Characterization of Two Closely Related Unclassifiable Endogenous Retroviruses in Pythons (Python molurus and Python curtus) 
Journal of Virology  2002;76(15):7607-7615.
Boid inclusion body disease (BIBD) is a fatal disorder of boid snakes that is suspected to be caused by a retrovirus. In order to identify this agent, leukocyte cultures (established from Python molurus specimens with symptoms of BIBD or kept together with such diseased animals) were assessed for reverse transcriptase (RT) activity. Virus from cultures exhibiting high RT activity was banded on sucrose density gradients, and the RT peak fraction was subjected to highly efficient procedures for the identification of unknown particle-associated retroviral RNA. A 7-kb full retroviral sequence was identified, cloned, and sequenced. This virus contained intact open reading frames (ORFs) for gag, pro, pol, and env, as well as another ORF of unknown function within pol. Phylogenetic analysis showed that the virus is distantly related to viruses from both the B and D types and the mammalian C type but cannot be classified. It is present as a highly expressed endogenous retrovirus in all P. molurus individuals; a closely related, but much less expressed virus was found in all tested Python curtus individuals. All other boid snakes tested, including Python regius, Python reticulatus, Boa constrictor, Eunectes notaeus, and Morelia spilota, were virus negative, independent of whether they had BIBD or not. Virus isolated from P. molurus could not be transmitted to the peripheral blood mononuclear cells of B. constrictor or P. regius. Thus, there is no indication that this novel virus, which we propose to name python endogenous retrovirus (PyERV), is causally linked with BIBD.
doi:10.1128/JVI.76.15.7607-7615.2002
PMCID: PMC136364  PMID: 12097574
13.  The Role of In Vitro-Induced Lymphocyte Apoptosis in Feline Immunodeficiency Virus Infection: Correlation with Different Markers of Disease Progression 
Journal of Virology  1998;72(11):9025-9033.
Human immunodeficiency virus infection is characterized by a progressive decline in the number of peripheral blood CD4+ T lymphocytes, which finally leads to AIDS. This T-cell decline correlates with the degree of in vitro-induced lymphocyte apoptosis. However, such a correlation has not yet been described in feline AIDS, caused by feline immunodeficiency virus (FIV) infection. We therefore investigated the intensity of in vitro-induced apoptosis in peripheral blood lymphocytes from cats experimentally infected with a Swiss isolate of FIV for 1 year and for 6 years and from a number of long-term FIV-infected cats which were coinfected with feline leukemia virus. Purified peripheral blood lymphocytes were either cultured overnight under nonstimulating conditions or stimulated with phytohemagglutinin and interleukin-2 for 60 h. Under stimulating conditions, the isolates from the infected cats showed significantly higher relative counts of apoptotic cells than did those from noninfected controls (1-year-infected cats, P = 0.01; 6-year-infected cats, P = 0.006). The frequency of in vitro-induced apoptosis was inversely correlated with the CD4+ cell count (P = 0.002), bright CD8+ cell count (P = 0.009), and CD4/CD8 ratio (P = 0.01) and directly correlated with the percentage of bright major histocompatibility complex class II-positive peripheral blood lymphocytes (P = 0.004). However, we found no correlation between in vitro-induced apoptosis and the viral load in serum samples. Coinfection with feline leukemia virus enhanced the degree of in vitro-induced apoptosis compared with that in FIV monoinfected cats. We concluded that the degree of in vitro-induced apoptosis was closely related to FIV-mediated T-cell depletion and lymphocyte activation and could be used as an additional marker for disease progression in FIV infection.
PMCID: PMC110319  PMID: 9765447

Results 1-13 (13)