Virologic, immunologic, and clinical follow-up of a couple infected by the human immunodeficiency virus type one, group O

Abstract

The pathogenic course (virologic, immunologic, and clinical changes) of infection due to human immunodeficiency virus type one (HIV-1) group O viruses is unknown at present. To address this issue, serial HIV-1 isolates from a married couple (patients A and B) infected with a group O virus were analyzed to determine the temporal association between disease status and alterations in several parameters including plasma viral burden as measured by semiquantitative polymerase chain reaction, changes in CD4+ T cells, presence of neutralizing antibodies, and the ability to induce syncytia on the MT2 cells. For patient A who has been asymptomatic for at least 8 years, both the absence of syncytium-inducing (SI) variants and the presence of autologous and heterologous neutralizing antibodies correlated with a clinically healthier status. In contrast, a switch from NSI to SI variants was observed in patient B in 1990, followed by an expanded in vitro host range, increased viral burden, and a sharp decrease in CD4+ T cells 4 years later. Moreover, plasma obtained from this patient uniformly failed to neutralize both autologous and heterologous viruses. These observations in patient B correlated with a slightly unfavorable clinical status. Based on our preliminary results, it appears that the pathogenic course of infections due to group O viruses is similar to that reported previously for infections due to group M viruses.

HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs

“…Infection by CCR5-using HIV-1 and the late appearance of CXCR4-using HIV in disease have also been studied in patients infected with HIV-1 group M. However, the prevalence and evolution of HIV-1 using specific coreceptors in group O infections are still poorly understood as only very few group O-infected subjects have been followed during disease. 48 This of course also has relevance to the use of MVC in group O-infected individuals. To further our knowledge on coreceptor usage among group O isolates, U87.CD4.CCR5 or CXCR4 cells were exposed to each of the 18 HIV-1 group O primary isolates and 1 group M/O (Tables 1 and 2).…”

Natural Residues versus Antiretroviral Drug-Selected Mutations in HIV Type 1 Group O Reverse Transcriptase and Protease Related to Virological Drug Failurein Vivo

“…Before therapy, after 7 years of follow-up, the viral RNA levels in the asymptomatic individual A were 2.5-2.8 log 10 copies of RNA per milliliter, and CD4 1 T cell counts had decreased from 500 to 150 cells/ml. 5 Individual B had lymphoadenopathy, baseline viral RNA levels between 3.1 and 3.6 log 10 copies/ml, and a concomitant decline in CD4 1 T cell count from 500 to 20-50/ml. The clinical stage, the assessed viral RNA levels, and CD4 1 T cell counts of both individuals were within the range of clinical parameters found in group M-infected persons.…”

“…Individual B developed lymphadenopathy, three episodes of furunculosis, and intertrigo, with CD4 1 T cell counts declining from 500 to 20-50 cells/ml. 5 Serum samples were taken from both individuals just before start of therapy (day 1) and at intervals during treatment. These samples were stored at 270°C, along with serum samples from the period between seroconversion and start of therapy, until used for analysis of HIV-1 RNA levels.…”

“…4 Although a relatively small number of group O-infected individuals has been monitored, the natural history of the group O viruses does not appear to differ substantially from that of group M viruses. 5 We have monitored the course of ANT70 infection in the index case (individual A) and her partner (individual B) since 1990. Both individuals have received antiviral therapy since 1995.…”

“…To date, the effect of antiviral therapy in such individuals has been examined primarily by the assessment of CD4 1 T cell counts and the approximation of HIV-1 group O RNA levels using a semiquantitative RNA assay that is able to detect group O virus infection. 5 The CD4 1 T cell count is an important marker, 11,12 but because of wide fluctuation it is insufficient to evaluate the effect of antiviral therapy. 13,14 Therefore, we developed a quantitative group O-specific viral RNA assay based on nucleic acid sequence-based amplification (NASBA) technology, with primers and probes validated for the ANT70 sequence.…”