Journal of ISSN: 2373-6453JHVRV

Human Virology & Retrovirology
Opinion
Volume 2 Issue 3 - 2015
Struggle with HIV: A Personal Experience of Bob Gerwig
Bob Gerwig*
Microsoft Software Tech, USA
Received:February 02, 2015 | Published: April 06, 2015
*Corresponding author: Bob Gerwig, Microsoft Software Tech, Seattle, Washington, USA, Email: @
Citation: Gerwig B (2015) Struggle with HIV: A Personal Experience of Bob Gerwig. J Hum Virol Retrovirol 2(3): 00043. DOI: 10.15406/jhvrv.2015.02.00043

Opinion

My Stage for AIDS Dx was in June 1991. I continued to work in Microsoft's Applications Division for another 12 months so my stock options could finish vesting. At the beginning of June 1992, my doctors told me to stop driving due to rapid cognitive deterioration which proved not to be "AIDS dementia," rather "slow progressive encephalopathy" and I got into bed and was bedridden for most of the 10 years: 1994-2004.

That's when my physicians started describing the changes in my condition as a miracle, and so did I. It lasted at "full-tilt-boogy" for 2 years, then a slight decline in the third year and a sharp drop in the ninth year, 2009. After being home-bound and in bed ca. 80-95% of the time 2009-2014, it has happened again.

Starting in July 2014, it is happening again on a deeper and more profound level for me mentally, emotionally and spiritually. And my HIV/AIDS scientific profile has broken all records tracking my levels. My immune system is rejuvenating at great speed. (Some say God speed).

Summary

  1. 1985.07.14: Exposed to HIV (Bastille Day) via Quaker boy friend who knew he was HIV+ but had told me he was in an HIV- control group in a clinical study for people HIV+. Not.
  2. 1985.10.02: A public nurse who was a friendly neighbor got to be the one to tell me there was no HIV- control group in that study. She said everyone in it was HIV+ and they all knew it, and I needed a blood test. This was late October. I went to that same hospital the next day, and a week later found out I was HIV+.
  3. It was 1985.10.31 confirmation HIV+ (Halloween in gay Seattle on public busses from 4-6pm. Surreal.)

  4. 1986: My HIV/AIDS- related & other blood work and lab results.
    CD4 ca.700.
    CD8 and their ratio unknown.
    HIV viral load unknown.
    Rx AZT in large doses.
  5. 1990: pre-AIDS deterioration:
    CD4 ca.550.
    ratio ca.10%.
  6. 1991.06.1: Dx'd w/Stage 4 AIDS
  7. 1992.06.01: Permanently disabled & taken off the road by physicians for bed and "permanent disability" and by 1998, was told I'd be taking morphine "for the duration." I asked, "The duration of what?" "Your life." And I've now taken morphine (except for 1992-93, replaced by Fentanyl) every day since then and for the duration.
  8. 1994-1998: Chronic and overlapping outbreaks of h. zoster ("shingles") on my right forehead and scalp. I was on high doses of opiates: CD4 usually in the 150-250 range with dips of 3-6 months in the 50-150 range. CD8 is?, with ratios down to 8-6%. Shingles-affected area grew along nerve lines on the area from my right eyelid up along the right supra-orbital nerve under my right eyebrow where it turned upward from the top of my nose and along the right side of center to the "baby's soft spot," infected nerves around the right rim, and also branching off to the right along my right forehead hairline forming a large figure-C from my perspective running from the outer end of my right eyebrow to the nose and up to the hairline and right on the scalp to about the tip of my right ear (not infected).
  9. 1998.03.1: 1st of 2 Radiofrequencies on the right supra-orbital nerve to try to knock out the frequency of the pain transmission. It worked very well but only for 3 months, then again for 6 weeks with 1-2 weekly injections of Lidocaine into my right supra-orbital nerve for a rush of cold "water" putting out fires. So we decided to make it permanent, on:
  10. 1998.05.2: Neurosurgeon ablated right supra-orbital nerve, accessing it by incision along top of eyebrow. The results were an unanticipated spectacular success and received well by all. It broke the never-ending outbreaks of the previous four years. And I had the IV morphine catheter of 11 months removed in one month and have been on a maintenance dose of Morphine Sulfate ER tablets 30mg/bid. and currently am preparing to step it down to 15mg/bid. as it was before 2004. I still get small outbreaks of shingles when I'm tired, stressed and am sick with something else (e.g., cold, flu, whooping cough for 9 months overlapping with laryngitis for 6 months, a staph infection becoming an abscess to be lanced, then it became non-necrotic MRSA, etc. - all of which I've had and much more).
  11. 1994-1996: MS-Contin 30mg/t.i.d. My peristaltic motion in my intestines was so disrupted, I had dehydrated bowel blockages.
  12. 1996-1997.05: Fentanyl trans dermal patches: 100micrograms/hour x 3 patches at once every 3 days. "HIV Night [& day] sweats" caused the patches to fall off sooner than 3 days in random order causing endless narcotic withdrawal and insufficient pain relief. I had other neuralgias developing in my face, arms and legs plus peripheral neuropathy in my hands, and severely in my feet (still). I also felt like I had”phantom tropical sunburn from head to toe. There was no redness, just the sensation. Any physical touching, even shaking hands and especially receiving hugs became unpleasant for me and I had to tell people no more.
  13. 1997.05.1: Began IV morphine in saline with a baseline of 22mg/hr with 3 optional boluses/hr of 8mg each. I was on palliative care at home for 11 months of home nursing to change the dressing on the catheter in my arm and change sides when needed. I knew the password on the pump and was receiving a 10-day bag of morphine in saline every 7 days. It was very tempting, but I went into hospital to die by refusing nutrition and hydration except for morphine, saying it was insufficient to manage the pain to increase the morphine legally until I stopped breathing which would be a Dx of "complications due to AIDS" rather than "suicide." But at the last minute I pulled out of it. My daughter was in high school (class of 2000).
  14. 1998.04.1: 11 Months after beginning palliative IV morphine averaging 30mg/hr/day. I felt despair. Several days later, still in the hospital with no options, my doctor introduced me to a neurologist and a neurosurgeon. Long story, but six months later the IV catheter was removed and I began taking MS-Contin again @ 30mg/t.i.d., then bid., then 15mg bid., but that was as low as I could go without unmanageable pain.
  15. 1999-2004: Averaged MS-Contin/Morphine Sulphate ER ranging from 15mg-30mg bid
    1999-2001: CD4 in 250-350 range
    2001-2004: CD4 in 300-450 range
    2004-2010: CD4 in 350-450 range. 
  16. 2010.10.10: Moved out of condo of 19 years and neighborhood of 26 years for a condo better suited to me in a very different neighborhood, moving from Capitol Hill to Lake City in northeastern Seattle.
  17. 2010: CD4 broke 500 for the first time since the 1980s. Then it broke 600 and I'm currently and consistently in the mid-600s with a ratio with CD8 at 12-16%. My HIV viral has been undetectable for years. 
  18. 1991-2000: HIV viral load in 2-3 million range during acute illness, then down to 100,000-300,000 and finally undetectable except for two brief spikes to 10,000 and a second time to 2,000.
  19. 2014.07.03: 2nd major healing in 10 years began.
  20. NOW: 2015.01.10: Current level for three years has been Morphine Sulphate ER @ 30mg bid. and I've switched to the same dose in 15mg pills to start to decrease my maintenance baseline dose as my pain is much reduced since last Summer.

Introduction

Human immunodeficiency virus 2 (HIV-2) is less virulent in vivo compared to human immunodeficiency virus 1 (HIV-1). This reduced virulence is revealed by a longer asymptomatic period, minor T-cell depletion and lower viral load. The basic molecular mechanisms, (both viral and cellular) underlying this reduced virulence is far from being fully characterized or even identified. We hypothesize that the way HIV-2 interacts with cellular receptors contributes decidedly to this lower virulence and enables the preservation of host immune function for a longer period of time. In this review the main characteristics of HIV-2 interaction with cellular receptor are focused and the major differences to HIV-1 are highlighted.

Discussion

Disease progression in HIV infection is accompanied by a continuous and irreversible decline of CD4+ T-lymphocyte numbers, predisposing the host to life-threatening opportunistic infections. Understanding the mechanism of CD4 cell loss in HIV infection is essential to understand viral pathogenesis and for the development of effective therapeutic strategies. In this regard, HIV-1 and HIV-2 show some important differences in vivo. Although sharing the same transmission routes, HIV-2 infection is in general characterized by:

  1. A longer asymptomatic stage
  2. A lower viral load
  3. A minor T-cell depletion and consequently to a lower rate of disease progression (reviewed in [1,2]).

In fact, despite both viruses are linked to the onset of Acquired Immunodeficiency Syndrome (AIDS), HIV-2 infection has little impact on survival of infected individuals [3-5]. These observations lead to the assumption that virtually all HIV-2 infected patients fit in a definition of "long-term non-progressors" or "elite-controlers", a condition that appropriately define those rare HIV-1 infected individuals [6]. That remains healthy for several decades without any antiretroviral therapy, with undetectable plasma viral load and CD4+ cell counts above 500 cells/μL.

The initial events that lead to viral entry have been related to several important characteristics of HIV. Modifications, either in cellular receptors or in viral receptor-interacting glycoproteins, lead inevitably to major viral phenotype changes that include adjustment of cell tropism, altered replicative fitness, different abilities to induce T-cell depletion or to escape neutralizing antibodies and, ultimately, to unique pathogenic characteristics. In the most favored model(reviewed in [7,8]), HIV entry begins with a specific interaction between the virion heterodimeric Env complex, formed by surface (SU) and trans membrane (TM) glycoproteins, and two cellular proteins: CD4 and a chemokine receptor (referred as co receptor). Several of these receptors have been described in vitro as potential cofactors for HIV entry into target cells. However, despite this extensive range of molecules that could act as viral co receptor, CCR5 and CXCR4 are considered as the main coreceptors for HIV-1 and the only that has a well-defined role in HIV pathogenesis[9,10].
Based on our previous work we hypothesize that one of the factors that greatly contributes to the lower virulence of HIV-2 is related with the efficiency with which HIV-2 uses cellular receptors to interact with target cells. This hypothesis stems from our previous observation regarding CD4-independent infection [11] and non-usage of neither CCR5 nor CXCR4 by HIV-2 strains [12-15].

These observations clearly support the notion that HIV-2 and HIV-1 use cellular receptors in different ways with direct implications in viral pathogenesis [1]. Furthermore, the molecular determinants of coreceptor engagement seem also to be different in HIV-1 and HIV-2. While in HIV-1 the variable region 3 (V3) of Env SU glycoprotein is the major determinant of coreceptor usage [16-19], in HIV-2 the contribution of V3 region seems to be much less defined. In this regard, we recently show [12] that the use of CCR8 as coreceptor and the switch from CCR8 to CCR5 or CCR5/CXCR4 usage is determined by amino acids located in variable regions 1 and 2 (V1/V2) of HIV-2 SU envelope glycoprotein.

The usage of cellular receptors by HIV enables the virus to overcome the plasma cell membrane barrier and permits the delivery of its genetic material into host cell cytoplasm. In addition, the interactions between HIV Env glycoproteins with coreceptor and the misappropriation of chemokine receptor function, triggers the activation of several intracellular pathways that leads to an array of physiological changes in infected cell (e.g. chemo taxis, proliferation, cytokine secretion, differentiation). Although receptor signaling is not required for coreceptor function [20-22], these chemokine signaling cascades in vivo may prepare the target cells for viral replication and conceivably they could be responsible for some of the cellular responses to the virus [23].

One of them is the induction of apoptotic signaling. This HIV mediated apoptosis is largely responsible for the gradual depletion of CD4+ T-lymphocytes, although other mechanisms have also been described. Although HIV encodes several apoptogenic proteins (e.g. Env, Tat, Vpr, Vpu and Nef), Env interaction with cellular receptors has been consistently referred as a principal mechanism of T-cell apoptosis [23]. The mechanisms underlying this programmed cell death are directly dependent on Env glycoprotein and the way it interacts with cell receptors (reviewed in [24]). Accordingly, different Env proteins with different coreceptors usage profiles induce different signaling pathways and conceivably could induce different levels of apoptosis in infected and bystander non-infected cells [25].

In addition, it was shown [26] that HIV-1 is able to bind and signal through the integrin alpha4-beta7 (α4β7) that mediates the migration of lymphocytes to gut-associated lymphoid tissue (GALT). Regardless of the route of transmission, HIV-1 rapidly establishes infection in GALT, converting this lymphoid tissue in the principal site of viral replication, followed by a severe CD4+ T-cell depletion [27,28]. The slower rate of CD4+ T-cell decline in HIV-2 infection may reflect differences during the initial phase of HIV-1 and HIV-2 infections and directly related with GALT infection. Since HIV-2 induces a naturally less pathogenic infection, an obvious question arises: is HIV-2 interaction with α4β7 as efficient as HIV-1? And does this interaction leads to the same sort of cellular signaling such as the activation of LFA-1, an integrin that facilitates cell-to-cell transfer of HIV through the induction of virological synapses [29]? Although these effects are hypothetically viral strain-dependent, we hypothesize that HIV-2 may interact with α4β7 less efficiently leading to a minor colonization of the GALT and hence to a lower depletion of CD4+ T-lymphocytes.

Conclusion

Very few data exists about the cellular consequences of HIV-2 interaction with cellular receptors. The plasticity of HIV-2 Env SU glycoprotein, leading to an unusual profile of coreceptors usage, could allow HIV-2 to “accidentally” infect inappropriate cell populations or induce less-than-optimal signaling after interaction with cellular receptors and thus be responsible for abortive infections, lower viral yields and minor T-cell apoptosis. It is thus important to assess the outcome of these interactions since them could explain the attenuated disease of HIV-2. Further studies are of utmost importance focusing in particular viruses obtained from asymptomatic individuals, since the main differences between HIV-1 and HIV-2 pathogenesis are particularly striking during this stage where a significantly slower clinical progression and lower CD4+ T-cell depletion are observed.

Acknowledgement

This work was supported by a grant from Fundação para a Ciência e Tecnologia and Ministério da Saúde de Portugal (Grant VIH/SAU/0006/2011).

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