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Q. Will an HLA-B35/58 person produce antibodies against HIV?

Answered by
Dr. Ravinder Kaur Sachdeva
and medically reviewed by iCliniq medical review team.
This is a premium question & answer published on May 23, 2018 and last reviewed on: Nov 29, 2022

Hello doctor,

I have studied that HLA-B35, HLA-B58, and HLA-B7 are responsible for the rapid progression of AIDS and often test false negative when tested. However, with C clade virus it is somewhat protective and does not lead to rapid disease progression which has something to do with the CD8 T cell response to a single gag epitope which is only available in the C clade virus. I want to know will an HLA-B35/58 person be infected with C clade virus and produce antibodies to HIV unlike in B clade virus? Also, what causes a false negative in B clade?

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Hello,

Welcome to icliniq.com.

  • Yes, HLA-B35/58 (human leukocyte antigen) person will be able to produce antibodies against HIV-1 (human immunodeficiency virus). This is true for all clades.
  • The immunogenic response is known to be somewhat greater in clade C due to a higher diversity of immunogenic epitopes on p17 and p24 gag (group-specific antigen) protein.
  • Clade B is known to be less diverse leading to a lower CD8 (cluster of differentiation 8) response and also due to the presence of an escape mutant at a higher frequency.
  • A completely negative serology is an extremely rare phenomenon.
  • Some clade-specific differences in p17 gag epitope result in non-immunogenicity in clade B. However, only few case reports of non-reactive serology are known and are not often seen.

Best wishes.

For more information consult an HIV AIDS specialist online.

Hello doctor,

Thank you for the reply,

1) Is it possible that clade-specific differences in p17-GAG epitope that result in nonimmunogenicity in clade B might also happen in clade C? Have there been cases regarding this?

2) Is a false-negative possible in clade C of HLA B 35, HLA B 58, or any other alleles related to nonimmunogenicity, in 4 ELISA/EIA second-generation tests in a duration of eight years after possible exposure?

3) What else might cause false-negative EIA second-generation test in clade C besides window period, terminal stage AIDS and HAART reconstitution?

Thank you so much for your help. Please provide a 100 % accurate answer, and I do not want to doubt the possibility. I do not know where else to ask for help.

#

Hi,

Welcome back to icliniq.com.

1) There are multiple proteins and multiple epitopes responsible for overall immunogenicity. Single epitope may contribute to some extent in influencing the immunogenicity, but may be not be sole factor. Immunogenicity can be cellular or humoral. In what context you are asking. There is vast literature available and limited discussion on this forum by texting might not be sufficient.

2) Refer above.

3) Secondary immunodeficiency caused by immunosuppressant drugs or primary immunodeficiency. There seems to be mismatch in the age and gender in the two queries asked by you.

I hope your queries are answered.

Best wishes.

Hello doctor,

Thank you for the reply,

My last possible exposure was in 13 years back and ever since that time I have done four HIV 1 ELISA or EIA antibody tests. This tests were second generation tests as they simply looked for HIV 1 specific antibodies in the serum. The last test I took in seven years later second generation again, as the test mentioned antibodies only. Now all this test resulted Negative/Non-reactive. I do not have primary immunodeficiency and I never took any immunosuppressant drugs before any of my tests. But I cannot be at peace for the possibility of HLA B-35/58 discussions that I have found on the internet forums that result in false-negative in patients. What if I have got this HLA and this is making my tests false-negative even in clade C which is prevalent in India. Is there a possibility that this could happen in clade C too? I want to be sure that I do have time, and want to make the best of myself without living in fear every single day.

#

Hi doctor,

Welcome back to icliniq.com.

1) Your test results are conclusively negative for HIV (human immunodeficiency virus).

2) You can surely relax and move forward.

3) It is extremely and extremely unlikely that a person remains seronegative for almost eight years of infection.

4) It is also extremely and extremely unlikely that progressive HIV symptoms do not manifest during eight years of infection.

5) Although you have not described the nature of HIV exposure.

6) Not all exposures lead to HIV. Bottom line: You are not HIV infected.

Finally: Go ahead. Make best of yourself. You can still ask me if there are more doubts or you can also book an appointment for clarifications.

Best wishes.

Hello doctor,

Thank you for the reply,

My question is still not answered. Nature of my possible exposure was vaginal with my former boyfriend who had a loose character. I do not know about his HIV status. But I use to suffer severe migraines, skin rashes, recurrent sore throat, myalgia, weakness (over six months), chronic back ache (over nine years). I was recently diagnosed with spinal stenosis and bulging disc, without secondary spinal stenosis. I have read that spinal pain, spinal stenosis and disc-degeneration problems are common in primary HIV 1 infection.

My questions are:

1) Other then clade B, is there any possibility for my test to result false-negative to HIV-1 clade C if I am HLA-B*35,*58, A*02 or any other alleles? Or both B and C clades with these HLAs by far will produce same amount of anti HIV antibodies that might or might not be detected. Please describe.

2) Are there any reported cases of the above?

3) Can long term non-progressors like HLA-27, HLA-57 test false-negative due to minimal virus in their body.

Thank you so much.

#

Hi,

Welcome back to icliniq.com.

In my experience in treating more than ten thousand HIV patients over last thirteen years, I am yet to come across such a scenario. In addition, negative HIV serology beyond window period in immunocompetent person having any HLA combination, infected with clade C virus, tested with available fourth generation HIV test kits is not in my knowledge. That is the closest I can get in answering your question. Although absolutely not required, but, if you are still in any doubt, go for HIV RNA testing.

Best wishes.

Hello doctor,

Thank you for the reply,

Sorry to be questing you again, but I just came across a forum that has been bothering me.

1) Can HIV superinfection, CRF (circulating recombinant form), co-infection or dual-infection, drug resistance infection from someone or any type of hybrid HIV virus cause false-negative antibody serology that was done four times during eight years after infection?

2) My Possible exposure was with one person eight years ago who could have had a superinfection and I may have a new recombinant strain or a superinfection that is causing the test to be negative? Is there any possibility?

4) What would be the window period (if) of such viruses to produce antibodies?

3) Doctor from online had recommended a PCR (polymerase chain reaction) test to someone who tested negative but the person is not sure himself if he was truly hiv infected.

Is a PCR necessary for me to rule out such viral strains, as I don't want to go for something that is not really necessary?

Thank you so much.

#

Hi,

Welcome back to icliniq.com.

The answers to your queries are:

1) This seems unlikely.

2) No.

3) Window period is the time taken for antibodies to develop in the body after infection and then to be detected by a particular test kit. With the recent available fourth generation HIV testing kits, the kits are able to detect antibodies by four to six week of the exposure, if infected and a confirmatory test can be done at three months if earlier test is negative.

4) The recommendations are to get tested by an antibody test. But there is no harm in getting HIV RNA PCR. This test is expensive.

Best wishes.

Hi doctor,

Thank you for the reply,

Just have one last question for you. Can an EIA antibody test (looking for both antibody and antigen but the test mentioning only antibody) after the three months window detect all types of CRFs such as A/E, A/B, C/B, and all other B or non-B subtypes? Are there any subtypes that an EIA antibody test cannot detect? I am extremely worried that some CRF of B subtype or any other CRF that an EIA test cannot pick up is causing my tests to be negative.

Thanks.

#

Hi,

Welcome back to icliniq.com.

You can send your report for further interpretation. If you do not have it, get a fourth-generation HIV rapid test or even a western blot test which is highly sensitive and specific.

Please revert if any other information is required.

Best wishes.

Hi doctor,

Thank you for the reply, This is context to my fist question to you, I know i'm panicking a lot over this, but I need to know certain answers to clear out my mind. My question to you was:

I have studied that HLA B-35, B-58, B-07 are responsible for rapid progression to AIDS and often test false negative when tested. However with C clade virus. It is some what protective and does not lead to rapid disease progression which has something to do with CD8 T cell response to a single GAG epitope which is only available in C clade virus. I want to know, Will a HLA B-35/58 person infected with C clade virus produce antibodies to HIV unlike in B clade virus and what causes false negative in B clade. To which your reply was: yes, HLA B35/58 person will be able to produce antibodies against HIV 1. This is true for all clades. The immunogenic response is known to be somewhat greater in clade C, due to higher diversity of immunogenic epitopes on p17 and p24 GAG protein. Clade B is known to be less diverse, leading to lower CD8 response and also due to presence of escape mutant at a higher frequency. A completely negative serology is extremely rare phenomenon. Some clade specific differences in p17-GAG epitope result in nonimmunogenicity in clade B. however, only few case reports of non reactive serology are known and are not often seen. My question is:Clade B is known to be less diverse, leading to lower CD8 response and also due to presence of escape mutant at a higher frequency. A completely negative serology is extremely rare phenomenon. 1) Will these people have rapid progression to AIDS? or is there a possibility that they do not progress to AIDS rapidly but might test negative for HIV in rare cases? I have done both a 4th generation and a western blot test-both the results are negative. 2) Do they look for all subtypes of HIV A,B,C,D,E,F,G,H,I,J,K and the CRF's of the following, can these tests miss out any crf combination between A-K, other than missiong out N and O group which I cannot have?

#

Hi,

Welcome back to icliniq.com.

1) Some clade B subtypes are known to progress slower than other types, however, it would be difficult to contemplate progression of any one seronegative case due to its extreme rarity.

2) Serological testing with presently available kits either have synthetic peptides representing viral protein regions which are difficult to miss, or have multiple epitopes, as in western blot, so that antibodies for at least few are easily detected. Hence missing on serology with prescribed algorithm will make missing nearly impossible. Clade or subtype determination comes later. Genetic subtyping can in most cases classify virus in one or more type. Odd and rare CRFs can be determined on sequencing of viral genome.

Hi doctor,

Thank you for the reply,

1) In C-clade infection, is the immunogenic response always known to be somewhat greater than in B-clade despite being any HLA alleles like HLA-B57/35/07:02? Or certain HLA alleles are responsible for a higher diversity of immunogenic epitopes on p17 and p24 GAG protein in the c clade.

2) Some clade-specific differences in the p17-GAG epitope result in nonimmunogenicity in clade B. Does this type of nonimmunogenicity result in rapid disease progression? Can this nonimmunogenicity result in a complete negative western blot? As it is in my case.

3) This is regarding my last query. Serological testing with presently available kits either has synthetic peptides representing viral protein regions that are difficult to miss or have multiple epitopes, as in western blot, so that antibodies for at least a few are easily detected. Hence missing serology with the prescribed algorithm will make missing nearly impossible so that antibodies for at least a few are easily detected. Did you mean antibodies for a few viruses from A-K or a few antibodies to a single virus are easily detected? Does the HIV virus produce multiple antibodies to a single virus, and that western blot might not yield reactivity to all the antibodies of a virus but at least a few antibodies are always detected?

#

Hi,

Welcome back to icliniq.com.

1) Generally immunogenic response of C is more than B but may not hold true for a given case.

2) Unlikely, western blot identifies multiple epitopes. In addition, fourth-generation kits identify viral antigens themselves besides identifying viral antibodies.

3) I meant at least some of the epitopes. HIV produces multiple antibodies against epitopes. Unlikely to be missed by western blot.


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