Abstract
Summary
We report a case of HIV-1 infection transmission caused by a fist fight between brothers. A 30-year-old Caucasian UK resident man developed ‘flu-like illness with symptoms of lethargy and weakness. Persistent lymphadenopathy six months later lead to HIV antibody testing, which was positive. Of note, his 37-year-old brother, who was HIV antibody-positive since August 2000, was taking HAART (combivir and nevaripine) with CD4 350 × 106/L (16%) with viral load 4800 copies/mL (log 2.58). A bloody fight had occurred between them four weeks prior to onset of symptoms. Phylogenetic analysis was undertaken. Analysis of the pol gene region indicated that samples from both brothers belonged to the subtype C clade of HIV-1, and that the sequences were closely related to one another. Exposure risk data are extremely useful in helping counsel patients prior to HIV-testing but, as this case illustrates, does not cover all situations.
INTRODUCTION
Monitoring the probable route of HIV-1 infection is important; it provides data from which potential risk of infectivity per episode can be calculated. This enables clinicians to advise and counsel patients on risk. We report an unusual case of HIV transmission, which would be missed by standard assessment of risk, e.g. evaluation of sexual, occupational, transfusion and injecting drug use (IDU) history. More unusual transmission such as contaminated equipment, blood contact, and direct inoculation are not routinely enquired about, or included in counselling regarding infectivity, prior to HIV antibody testing. This is appropriate as these modes are seen infrequently but they should be borne in mind. We also discuss the use of phylogenetic analysis in assessing possible transmission pathway.
CASE HISTORY
A 39-year-old Caucasian, married man developed flu-like symptoms with lethargy and weakness. Persistent lymphadenopathy prompted a lymph node biopsy six months later. Findings were consistent with changes associated with HIV infection. A subsequent HIV antibody test was positive.
This man was married (wife also Caucasian). He had no previous sex partners. There was no history of IDU, no blood transfusion, no occupational risk or tattooing. Of note, his brother had tested HIV antibody positive in 2000.
The brother is a 37-year-old heterosexual who contracted HIV infection in Botswana two years previously. Our patient was aware of this status.
A bloody fight occurred between them 4 weeks prior to onset of symptoms, no biting was reported. Both brothers had consumed considerable alcohol before the fight broke out. Neither of them sought medical attention afterwards or considered post-exposure prophylaxis.
Our patient's brother was on highly active antiretroviral therapy (HAART) (combivir and nevaripine) at the time of the fight, with CD4 350 × 106/L (16%), VL 4800 copies/mL (log2.58).
INVESTIGATIONS
Phylogenetic analysis was undertaken to determine if this was a mode of transmission. Permission was received from both patients and counselling was initiated. Samples were sent for reverse transcription, PCR amplification and genotyping. This was preformed for genomic regions −gag, pol + env.
Primer combinations were used to amplify more diverse viruses, as well as the more common Group M subtypes.
It was possible to generate amplicons in the pol gene from both samples from our case but only from one of his brother's samples. This may be because of several factors such as low viral load, due to HAART or natural immunological control or the storage and handling of the sample.
Analysis of the pol gene region indicated that each virus belonged to a subtype C clade of HIV-1, the most prevalent subtype among HIV-1 heterosexuals infected in southern Africa. The three pol sequences were closely related to one another. Sequences generated were not closely related to any other amplified and sequenced at any stage in the laboratory and therefore contamination is unlikely.
DISCUSSION
This is not the first account of transmission via a fight, Gilbart et al. 1 reports two cases both occurring in 1991. Both involved profuse bleeding during fights among strangers were the HIV status was unknown. However, in this case both were aware that one brother was HIV-1 infected. According to estimated risk of HIV transmission per exposure that via mucous membranes is approximately 0.09% 2 per episode. This case involved probable wound and mucus membrane exposure and the risk will vary greatly with amount of infected blood in contact with these surfaces. The history in this case suggested significant mixing of blood with a detectable HIV-1 viral load.
Other reports of transmissions via bites have been also reported. 3 The Center for Disease Control and Prevention, on the basis of their two cases, concludes that there must be blood in the mouth of the biter (HIV-1 infected) for transmission to occur.
It is currently not possible to be certain when and how HIV infection occurs. Phylogenetic methods are useful to investigate HIV-1 sequences for epidemiological, clinical or forensic purposes. However, they can only infer links. They do not indicate the direction of the infection, nor does it prove that other individuals could not have been involved in a series of intermediate events. 4 HIV-1 has a high replication rate of about 109 copies per day. 5 Because of the huge error rate there is a degree of variability between the different virus isolates at the genomic level. 6 The degree of variation should depend on the time elapsed since the transmission event, the rate of evolution of various parts of the genome and degree of immunoselection and/or drug selection for the different gene proteins. 7 Therefore, even known directly transmitted virus from one individual to another will have variation, which will increase over time, on phylogenetic analysis. 8 This variation will leave room for doubt especially if this test is being used in a forensic setting.
Due to the great increase in frequency of genotypic resistance testing, 9 many laboratories now have large databases of pol gene sequences such that Hue et al. 10 concluded that analysis from this region alone is sufficient for reconstruction of transmission events. That is these laboratories have large numbers of samples that can be used in quality assurance.
Exposure risk data is extremely useful in helping plan prevention strategies and in pre- and post-HIV antibody test discussions. Non-sexual contact is not usually included in these discussions since guidelines in this area concentrate solely on sexual acquisition. 2 Use of social drugs 11 and alcohol also impact on risk taking behaviour, this should be included in history taking.
Gilbart et al. 1 remind us that only three cases of unsuspected and unusual transmission have been detected among the seven million or more blood donors tested since screening was introduced in October 1985. 1 These cases are rare and are followed up by the Public Health Laboratory Surveillance in depth to ensure early grasp of new or unusual paths of transmission.
We present this subject to highlight the importance of careful history taking and illustrate the use of phylogenetic analysis. Exposure risk data are extremely useful in helping counsel patients prior to HIV testing but as this case illustrates must not be used in a rigid way.