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|Year : 2014 | Volume
| Issue : 1 | Page : 75--76
Slow progressor of human immunodeficiency virus: 20 years follow-up of a case from North India
S Sehgal, RW Minz, B Saikia, N Pasricha
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh
A case of human immunodeficiency virus (HIV) infection from North India is described with a 20-year follow-up. Patient first reported in 1993 when he was detected HIV positive, remained healthy without treatment, married in 1999 and did not transmit the disease to his children or his wife and was lost to follow-up. He was thought to be an elite controller. After 15 years of the initial visit, his CD4 cells, however, were found to be low, with a viral load of 10,000/copies/ml. He was negative for human leukocyte antigen B57 and B27 alleles with a normal expression of CCR5 and CXCR4 on CD4 cells. Lymphocytes showed a significant production of tumour necrosis factor alpha and interferon γ, but not of interleukin (IL)-2, IL4 or IL10. It is possible that gut infection, common in India, could have triggered T cell activation in the ensuing years, resulting in activation of HIV. The case illustrates the significance of long-term follow-up of these patients for timely institution of anti-retroviral therapy.
|How to cite this article:|
Sehgal S, Minz R W, Saikia B, Pasricha N. Slow progressor of human immunodeficiency virus: 20 years follow-up of a case from North India.Indian J Med Microbiol 2014;32:75-76
|How to cite this URL:|
Sehgal S, Minz R W, Saikia B, Pasricha N. Slow progressor of human immunodeficiency virus: 20 years follow-up of a case from North India. Indian J Med Microbiol [serial online] 2014 [cited 2020 Feb 27 ];32:75-76
Available from: http://www.ijmm.org/text.asp?2014/32/1/75/124325
Ever since Learmont et al.  from San Francisco city clinic documented precise determination of timing of human immunodeficiency virus (HIV) infection from stored samples, scientist over the world have recognised a peculiar group of HIV positive patients who do not progress to develop full blown acquired immunodeficiency syndrome (AIDS) and remain healthy without any antiretroviral treatment. In the Sydney blood bank cohort studies,  deletion of the NEF gene was thought to be the cause of disease non-progression Recently, attention has been focused on to host factors , more than ever before. The present paper describes an unusual case of HIV who remained well for nearly 15 years and then started to show signs of progression needing therapy.
This paper reports a case of patient X with aged range of 23 years, reported to the AIDS surveillance centre in 1993 because he was found to be HIV positive while donating blood for a relative in Haryana. On special interrogation, he gave a history of unprotected sex with a stranger. He was confirmed to be positive by ELISA, Immnunocomb (Israel) and Western blot assay (Du Pont). He next visited in 1997 and was in perfect health with a body mass index of 22.35. At that time, he was retested for HIV, but there was no provision by the National AIDS Control Society to provide free antiretroviral drugs and he could not afford treatment, therefore viral load assay was not deemed necessary. He was lost to follow-up because the patient presumed that the test might be wrong as he was in perfect health. He married in 1999, but visited the hospital again only in February 2008, i.e. 9 years after marriage and nearly 15 years after the first visit and he was absolutely healthy and totally a-symptomatic. His wife was persistently HIV negative. He was hence thought to be an elite controller. However, at this time, his CD4 count was 212/mm 3 and platelets were 98,000/mm 3 . His children were now 8 years (female child) and 5 years (male child) and were negative for HIV. Ideally, there should have been a sequential report of CD4 assay, but since the patient was lost to follow-up for nearly 11 years, no such investigation could be carried out. In view of low CD4 count, investigations were repeated after 6 weeks, which showed a viral load of 10,000 ribonucleic acid copies/ml (Reliance Diagnostics, Mumbai, India). Only on specific interrogation, he gave a history of genital herpes 4 weeks ago. Patient was negative for both human leukocyte antigen (HLA) B27 and B57 antigens. His CD4 lymphocytes showed normal CCR5 and CXCR4 expression using the flow cytometry. A detailed cytokine profile done on BD FACS calibre (USA) using bead array after short-term culture of lymphocytes  showed high tumour necrosis factor alpha (TNFα) and interferon γ levels, but interleukin (IL)-4, IL10, IL12 and IL5 were low or undetectable.
On follow-up after 3 months of treatment at antiretroviral therapy centre with zidovudin 300 mg, lamivudine 150 mg and nevirapine 200 mg twice a day (ﬁxed formulation as per National AIDS Control Organisation guidelines), the CD4 cells increased to 370/mm 3 with CD8 cells of 1654/mm 3 and he remained in good health until the time of the last reporting (August 2013). This case illustrates the fact that apparent "elite controllers" should be followed-up rigorously to assess any failing immune parameters so that they can get timely help. He appeared to be an elite controller to begin with but in retrospect, he fits in as a slow progressor as eventually his CD4 cells declined after 14-15 years, genital herpes being the first and only indication.
Cohort studies have indicated that the likelihood of disease progression and transmission markedly diminishes at viral loads below 2000 copies/ml of plasma. Recently, host genetic factors that control HIV replication are under extensive investigation. , Single nucleotide polymorphism (SNP) studies conducted by Goldstein  indicate that p5 (HCP5) SNP mediates its effect by virtue of linkage with the HLAB*5701. Patient was negative for HLA B27 and B57 alleles. Another SNP in the gene encoding HLA-C is also involved in presentation of epitopes to CD8 cells. The cytotoxic CD8 cell's several potential functional markers, e.g. IL2, TNFα, nuclear factor γ, macrophage inflammatory protein 1β along with a cell surface molecule called CD107 also play a crucial role.
Immune activation results in a higher rate of activated T cells: the preferred target of HIV. Douek's group  reported that translocation of microbes/microbial products across the gut contribute to immune activation. It is quite possible that such patients remain well for a long time until the balance is tilted as a result of gut or other infections and the disease may show progression.
Neil et al.  postulate that HIV lacking an accessory protein viral protein U remained tethered to the surface of non-permissive cells and this property could be induced by treating with TNFα. Several groups showed that HIV targets and destroys T helper 17 (Th17), a specialised group of IL17 secreting CD4 T cells discovered in 2005. Loss of Th17 cells leaves the body susceptible to bacterial, fungal and parasitic infections, which undesirably activate the immune system. In this activated state, CD4 T cells are the prime candidates for HIV infection and replication.  Th17 cells could not be estimated in this patient at that time.
Recently, there are two reports of long-term non-progressor children from Mumbai and Chennai, but the period of observation has been much shorter. ,
In India, HIV clade C predominates and it is known to be more avid for the CD4 cells.  It is important to understand this subset of individuals and their ability to control viral load than to assess them on the basis of the number of CD4 cells alone. The fact that this patient did not transmit the disease to his spouse for 9 years of marriage and nearly 15 years observation indicates that the viral load had been low until he visited in 2008. The case, the first of its kind from India, illustrates the importance of a close and sustained follow-up of apparent controllers for timely institution of therapy. A multicentre study of such cases investigating molecular events that limit viraemia may shed light on newer mechanisms involved in slow progressors.
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