HIV epidemic: From the origin towards the end.

Human immunodeficiency virus (HIV) is an RNA (ribonucleic acid) virus that infects human immune cells, specifically CD4 T lymphocytes and is acquired by means of mucosal or intravenous publicity to contaminated bodily fluids similar to blood, semen, and genital tract secretions. An infection from HIV was first reported in 1981 within the Morbidity and Mortality Weekly Report (MMWR), a publication of the Facilities for Illness Management and Prevention (CDC), when medical doctors found clusters of Kaposi’s sarcoma and pneumocystis pneumonia in gay males in Los Angeles, New York Metropolis, and San Francisco having weakened immune programs. In 1982, the CDC named the illness attributable to HIV as acquired immune deficiency syndrome, AIDS. (1) If left untreated, HIV infections progress from acute by means of continual to AIDS. Excepting a small proportion of untreated individuals contaminated with HIV who stay asymptomatic and present little proof of progressive immune suppression after 10 or extra years of an infection, almost all ultimately develop AIDS. The variety of AIDS circumstances grew in epidemic proportion and per the most recent United Nations AIDS factsheet, 85.6 million folks have develop into contaminated with HIV, and 40.4 million folks have died from AIDS-related sicknesses for the reason that begin of the epidemic. (2)

HIV has two subtypes–HIV-1 and HIV-2. HIV-1 has 3 main phylogenetic groups–M (main), O (outlier) & N (non-M, non-O), all of which might trigger AIDS. (3,4,5) HIV-1 M infections are frequent worldwide, O is restricted to West Central Africa and N is least spreading and was present in Cameroon. (3) HIV-1 group N is a mosaic of divergent HIV-1 and simian immunodeficiency virus (SIV) present in chimpanzees. (4,5) The HIV strains reported in the US in 1981 have been of HIV-1 subtype. Serologic proof of one other human immunodeficiency virus subtype (HIV-2) was found in 1985 in Senegal, (6) which was subsequently remoted in 1986 from a Cape Verdean affected person. (7) Round 95% of the folks contaminated with HIV are contaminated with HIV-1 subtype. HIV-2 is principally current in West Africa, however it’s slowly beginning to seem in different areas, together with the US, Europe, and India. (8)

Conditions that necessitate testing

HIV testing is required as follows:

* To find out the human immunodeficiency virus (HIV) an infection standing of an individual

* To check or display blood merchandise earlier than donation

* To judge the development of illness

* To observe the effectiveness of antiretroviral remedy (ART)

Assessments for HIV detection

HIV an infection might be detected within the following methods: (9)

* Direct visualization of HIV virus by electron microscopy

* Cultivation by lymphocyte tradition

* Measurement of HIV-specific serologic responses

* Detection of viral antigens

* Detection of viral nucleic acids

Nevertheless, the commonest checks use the immunological technique or the molecular technique. (10)

Enzyme-linked immunosorbent assays (ELISA)

The primary-generation HIV take a look at was an immunological take a look at that turned obtainable in 1985–the enzyme-linked immunosorbent assay (ELISA) detected IgG antibody of HIV-1 solely in sufferers 6 to 12 weeks after an infection. False-positive outcomes occurred; so optimistic outcomes wanted to be confirmed utilizing a second test–western blot or an immunofluorescence take a look at. The second-generation HIV take a look at turned obtainable in 1987 and had elevated specificity and optimistic predictive worth because it had a recombinant HIV-1 p24 antigen. Some checks included HIV-1 group O protein and an HIV-2 protein to allow detection of each HTV-1 and HIV-2 antibodies. The second-generation checks additionally decreased the antibody-negative window to 4 to six weeks post-infection an infection. The third-generation HIV checks added an IgM antibody and decreased the antibody-negative window additional to a few weeks post-infection. Within the late Nineties, the fourth-generation HIV screening assays have been launched that detected each antibody and p24 antigen for HIV-1 and HIV-2 mixed and decreased the test-negative to 2 weeks. In 2015, the fifth-generation HIV screening assay was launched that not solely detected each antibody and antigen for HIV-1 and HIV-2 but additionally differentiated between HIV-1 and HIV-2. (11) Desk 1 summarizes the evolution of HIV detection assays.

Molecular technique/nucleic acid take a look at (NAT)

Nucleic acid checks can be utilized as follows:

* To diagnose HIV sufferers

* To find out illness development and allow antiretroviral therapy monitoring

* Decide drug resistance characterization

A nucleic acid take a look at for HIV-1 was first demonstrated in blood specimens from HIV-1 contaminated people in 1988.13 It detects the HIV RNA and has the shortest window interval of 10 to 33 days post-infection. NAT is taken into account extra correct than ELISA checks and therefore used as confirmatory checks. Nevertheless, NATs are costlier than ELISA checks. The graph in Determine 1 depicts the window interval for the various kinds of checks –the NAT detects HIV the earliest post-infection, adopted by the antigen/antibody take a look at, and lastly, the antibody take a look at. (14)

HIV Screening and testing pointers

In the US, screening of blood donors for HIV-1 and HIV-2 began in March 1985 and June 1992 respectively. (15)

At current, the CDC recommends that everybody between the ages of 13 and 64 ought to get examined for HIV a minimum of as soon as as a part of their routine healthcare. These with sure ongoing threat factors–such as having a couple of intercourse associate since their final HIV take a look at or having intercourse with somebody whose sexual historical past they do not know–should get examined yearly. Some sexually energetic homosexual and bisexual males could profit from extra frequent testing (e.g., each three to 6 months). (16)

Specimen varieties for HIV testing embrace blood from a finger stick or within the type of serum, plasma, or dried blood spots (DBS). Oral fluid and urine specimens can be used for HIV testing. (17)

Illness development and analysis

There are three levels of HIV an infection, together with acute, continual, and AIDS. (18)

Acute HIV an infection: Develops inside two to 4 weeks after an infection. Some folks get flu-like signs, similar to fever, headache, and rash. HIV multiplies quickly and spreads all through the physique. The virus assaults and destroys the CD4 T lymphocytes. As the extent of HIV within the blood may be very excessive, the chance of transmission can be very excessive throughout this stage.

Power HIV an infection: Is the subsequent stage when HIV continues to multiply within the physique however at very low ranges and therefore the people are largely asymptomatic. They’ll transmit HIV to others but when the viral load is maintained at an undetectable degree taking antiretroviral remedy (ART), threat of HIV transmission is minimal.

Acquired immune deficiency syndrome (AIDS): Essentially the most extreme stage when the person’s immune system is broken and can’t battle off infections from opportunistic organisms.

There are two varieties of checks to judge illness development: HIV viral load and CD4 depend. HIV viral load checks are quantitative nucleic acid checks that decide the variety of copies of HIV RNA per milliliter of blood. They can be utilized to diagnose acute HIV an infection, information therapy decisions, and monitor response to antiretroviral remedy (ART). (19)

Determine 3: 4 pillars of Finish the HIV Epidemic (EHE) initiative by
HHS. (23)
The initiative focuses on 4 key methods:
DIAGNOSE all folks with HIV as early as potential.
TREAT folks with HIV quickly and successfully
to succeed in sustained viral suppression.
PREVENT new HIV transmissions utilizing
confirmed interventions, together with PrEP and
syringe service packages (SSPs).
RESPOND shortly to potential HIV outbreaks
to get wanted prevention and therapy
providers to individuals who want them.

CD4 depend dedication by immunofluorescence evaluation utilizing move cytometer is taken into account the gold customary. The conventional vary is between 500 to 1500 cells/cubic millimeter. For AIDS sufferers CD4 cell depend drops under 200 cells/cubic millimeter. (20) Determine 2 depicts the HIV viral load and CD4 depend throughout HIV development.

Ending the HIV Epidemic Initiative

With varied developments in HIV testing and therapy choices, the HIV epidemic has seen a decline with new infections declining. In 2019, the U.S. Division of Well being and Human Providers (HHS) launched an initiative that goals to cut back new HIV infections in the US by 90 p.c by 2030 (See Determine 3). (23)

Nevertheless, the emergence of drug resistant HIV strains has posed an important problem to profitable antiretroviral remedy (ART). (21) The HIV-1 pol gene is mostly used to establish mutations related to drug resistance and likewise for HIV-1 subtyping. (22)

Conclusion

It’s usually stated that “The place there’s a will, there’s a manner.” Tackling the HIV epidemic proves that time. The menace from the devastating HIV epidemic is now beneath management, due to the efforts by the assorted sections of society. Now, HIV testing will not be restricted to scientific labs and is accessible to the general public as point-of-care at-home checks. Therefore by following the tenets of EHE, one can stop an infection from HIV, and if by likelihood get contaminated, people ought to get identified and handled instantly to forestall improvement into AIDS.

REFERENCES

(1.) Gov H. Timeline of the HIV and AIDS epidemic. Hiv.gov. Printed November 15, 2023. Accessed December 14, 2023. https://www.hiv. gov/hiv-basics/overview/historical past/hiv-and-aids-timeline/.

(2.) World HIV & AIDS statistics–Reality sheet. Unaids.org. Accessed December 14, 2023. https://www.unaids.org/en/sources/fact-sheet.

(3.) Yang C, Sprint B, Hanna SL, et al. Predominance of HIV sort 1 subtype G amongst industrial intercourse employees from Kinshasa, Democratic Republic of Congo, AIDS Res Hum Retroviruses. 2001;1;17(4):361-5. doi: 10.1089/08892220150503726.

(4.) Yang C, Sprint BC, Simon F, et al. Detection of various variants of human immunodeficiency virus-1 teams M, N, and O and simian immunodeficiency viruses from chimpanzees through the use of generic pol and env primer pairs. J Infect Dis. 2000;181(5):1791-5. doi:10.1086/315439.

(5.) Fonjungo PN, Sprint BC, Mpoudi EN, et al. Molecular screening for HIV-1 group N and simian immunodeficiency virus cpz-like virus infections in Cameroon. AIDS. 2000;14;14(6):750-2. doi:10.1097/00002030-200004140-00018.

(6.) Barin F, M’Boup S, Denis F, et al. Serological proof for virus associated to simian T-lymphotropic retrovirus III in residents of west Africa. Lancet. 1985;21-28;2(8469-70):1387-9. doi:10.1016/s0140-6736(85)92556-5.

(7.) Clavel F, Guetard D, Brun-Vezinet F, et al. Isolation of a brand new human retrovirus from West African sufferers with AIDS. Science. 1986;18;233(4761):343-6. doi:10.1126/science.2425430.

(8.) Burgess L. HIV-1 vs. HIV-2: Variations and similarities. Medicalnewstoday.com. Printed December 5, 2018. Accessed December 14, 2023. https://www.medicalnewstoday.com/articles/323893.

(9.) Tang YW, Ou CY. Previous, current and future molecular analysis and characterization of human immunodeficiency virus infections. Emerg Microbes Infect. 2012;1(8):e19. doi:10.1038/emi.2012.15.

(10.) HIV testing. Cdc.gov, Printed June 9, 2022. Accessed December 14, 2023. https://www.cdc.gov/hiv/testing/.

(11.) Alexander TS. Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. Clin Vaccine Immunol. 2016;4;23(4):249-53. doi: 10.1128/CVI.00053-16.

(12.) 2018 Fast reference information: Advisable laboratory HIV testing algorithm for serum or plasma specimens. Printed on-line 2018. Accessed December 14, 2023. https://stacks.cdc.gov/view/cdc/50872.

(13.) Ou CY, Kwok S, Mitchell SW, et al. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988;15;239(4837):295-7. doi:10.1126/science.3336784.

(14.) Which HIV checks ought to I take advantage of? Cdc.gov. Printed June 1, 2023. Accessed December 14, 2023. https://www.cdc.gov/hiv/clinicians/ screening/checks.html.

(15.) U.S. public well being service pointers for testing and counseling blood and plasma donors for human immunodeficiency virus sort 1 antigen. Cdc.gov. Printed March 1, 1996. Accessed December 14, 2023. https://www.cdc.gov/mmwr/preview/mmwrhtml/00040546.htm.

(16.) Gov HIV. Sources for 2023 nationwide HIV Testing Day. Hiv.gov. Printed June 15, 2023. Accessed December 14, 2023. https://www. hiv.gov/weblog/resources-for-2023-national-hiv-testing-day/.

(17.) Ladies and HIV: Get the Details on HIV Testing, Prevention, and therapy. U.S. Meals and Drug Administration. Printed October 30, 2023. Accessed December 14, 2023. https://www.fda.gov/shoppers/womens-health-topics/ women-and-hiv-get-facts-hiv-testing-prevention-and-treatment.

(18.) The levels of HIV an infection. Nih.gov. Accessed December 14, 2023. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/ stages-hiv-infection.

(19.) Viral load take a look at. Hiv.gov. Accessed December 14, 2023. https://clinicalinfo.hiv.gov/en/glossary/viral-load-test.

(20.) Battistini Garcia SA, Guzman N. Acquired Immune Deficiency Syndrome CD4+ Depend. StatPearls Publishing: 2023.

(21.) Chimukangara B, Samuel R, Naidoo Okay, de Oliveira T. Major HIV-1 Drug Resistant Minority Variants. AIDS Rev. 2017;19(2):89-96.

(22.) Pasquier C, Millot N, Njouom R, et al. HIV-1 subtyping utilizing phylogenetic evaluation of pol gene sequences. J Virol .Strategies. 2001;94(1-2):45-54. doi:10.1016/s0166-0934(01)00272-5.

(23.) Introduction. Cdc.gov. Printed August 9, 2021. Accessed December 14, 2023. https://www.cdc.gov/hiv/insurance policies/strategic-priorities/mobilizing/introduction.html.

Rajasri Chandra, MS, MBA is a world advertising chief with experience in managing upstream, downstream, strategic, tactical, conventional, and digital advertising in biotech, in vitro diagnostics, life sciences, and pharmaceutical industries. Raj is an orchestrator of go-to-market methods driving full product life cycle from ideation to commercialization.

Caption: Determine 1: Window interval for NAT, antigen/antibody, and antibody take a look at for HIV. (14)

Caption: Determine 2: HIV viral load and CD4 cell depend as HIV progresses. (18)

Desk 1: Human immunodeficiency virus diagnostic testing. (11)
Era          1st                     2nd
12 months of launch      1985                    1987
Antigen (Ag)        Virus contaminated          Lysate and
supply              cell lysate             recombinant protein
Sensitivity         99%                     >99.5%
Specificity         95-98%                  >99%
Unfavorable window     8-10 weeks              4-6 weeks
Detects antibody    IgG Anti-HIV-1          IgG Anti-HIV-1 and
(Ab) and Ag                                 IgG Anti-HIV-2
Outcomes             Single outcome           Single outcome
Confirming checks    HIV-1 western blot      HIV-1 western blot or
                    or immunofluorescence   immunofluorescence;
                                            HIV-2 EU-SA and
                                            western blot if HIV-1
                                            is confirmed unfavourable
Era          third                       4th
12 months of launch      1991                      1997
Antigen (Ag)        Recombinant and           Recombinant and
supply              artificial protein         artificial protein
Sensitivity         >99.5%                    >99.8%
Specificity         >99.5%                    99.5%
Unfavorable window     2-3 weeks                 2 weeks
Detects antibody    IgG and IgM Anti-HIV-1,   IgG and IgM Anti-HIV-1,
(Ab) and Ag         HIV-2 and Group 0         HIV-2. Group 0 and
                                              HIV-1 p24Ag
Outcomes             Single outcome             Single outcome
Confirming checks    HIV-1 western blot or     HIV-1/HIV-2
                    immunofluorescence;       differentiation assay
                    HIV-2 EU-SA and western   adopted by HIV-1
                    blot if HIV-1 is          nucle-ic acid take a look at
                    confirmed unfavourable        (NAT) to substantiate
                                              neg-ative (8)
Era          fifth
12 months of launch      2015
Antigen (Ag)        Recombinant and
supply              artificial protein
Sensitivity         100%
Specificity         99.5%
Unfavorable window     2 weeks
Detects antibody    IgG and IgM Anti-HIV-1,
(Ab) and Ag         HIV-2. Group 0 and
                    HIV-1 p24Ag
Outcomes             Separate outcomes for
                    HIV-1 and HIV-2 Ab
                    and Ag
Confirming checks    HIV-1/HIV-2
                    differentia-tion assay
                    adopted by HIV-1
                    nucle-ic acid take a look at
                    (NAT) to substantiate
                    neg-ative (12)