Human Immunodeficiency Virus Type 1

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Human Immunodeficiency Virus Type 1
Virus classification
Group: Group VI (ssRNA-RT)
Family: Retroviridae
Genus: Lentivirus

Human Immunodeficiency Virus Type 1 (HIV-1) is an infectious human retrovirus that causes Acquired Immunodeficiency Syndrome (AIDS). HIV-I is commonly called HIV, although HIV is not the name of a viral species but is a term that refers to either HIV-1 or HIV-2.[1]

HIV-1 is primarily a sexually transmitted disease. Currently, HIV/AIDS kills approximately 2-3 million people per year, primarily in developing countries. Currently, in the U.S. there are approximately 500,000 people infected with HIV-I.

History

The history of HIV-1 has been detailed. [2] The association between opportunistic infections such as pneumocystis carinii pneumonia and homsexuality or intravenous substance abuse was first reported in 1981.[3][4][5] According to the United States National Library of Medicine, "prior to 1986, HIV was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2."[6]

Early on, as researchers struggled to determine the cause of the disease, several names were used by researchers and the press, including "gay-related immunodeficiency" (GRID) and "gay cancer", referring to the classic symptom of Kaposi's sarcoma[7]. HIV-1, at that time called human T-lymphotropic virus type III (HTLV-III), was first isolated from an infected patient in 1983.[8]

Widespread availability of the HIV test was in 1985.[9]

In the United States, zidovudine was approved for treatment of HIV-1 with a New Drug Application (NDA) by the FDA in 1987.[10]

Pathophysiology

After exposure, the virus invades and replicates in immune cells near the site of infection. It quickly spreads to regional lymph nodes and via the blood stream to the rest of the body. During this stage the patient may experience Acute Retroviral Syndrome, a vague flu-like illness. The patient is often asymptomatic for the first 5-10 years after infection. By that time, untreated, progression to AIDS in inevitable, except in a small subset of patients.

Clinical syndromes

Primary HIV infection

History and physical examination findings for primary HIV infection[11]
sensitivity specificity
Fever 88% 50%
Malaise 73% 58%
Myalgia 60% 74%
Rash 58% 79%
Headache 55% 56%
Night sweats 50% 68%
Sore throat 43% 51%
Lymphadenopathy 38% 71%
Arthralgia 28% 87%
Nasal congestion 18% 62%

Acquired Immune Deficiency Syndrome

For more information, see: AIDS.


Transmission

HIV is primarily spread by sexual contact. Most early infections in the United States were via homosexual sex, and to a lesser extent via intravenous drug use and blood transfusions; most current infections in the world are via heterosexual contact and vertical transmission from mother to child.

HIV can be found in various body fluids, however its highest concentrations are found in semen, blood, and vaginal secretions. It can also be found in breast milk; however exclusive breastfeeding tends to protect against HIV transmission.[12]

Other less likely means of transmission exist, though are rare. There are no confirmed cases from contact with the saliva, sweat or tears of an infected person.

Blood exposure

Mothers infected with HIV transmit the virus to their baby in utero, during childbirth. Mother-to-child transmission can be significantly reduced by the proper use of antiretroviral agents.

Less commonly, contact with infected blood causes HIV transmission. This can occur in health care providers (HCPs) or others exposed to infectious bodily fluids. Transmission is facilitated by breaks in the skin or direct contact with mucosal tissues, such as those found in the eyes, mouth, anus, or vagina. Early in the epidemic, blood transfusions were a significant source of HIV transmission.

Sexual contact

Risk of HIV transmission per sexual contact[13]
  Risk of transmission per act
Unprotected receptive anal sex
with a known seropositive partner
0.82%
Unprotected receptive anal sex
with a partner of unknown serostatus
0.27%
Unprotected insertive anal sex 0.06%
Receptive oral sex 0.04%

A cohort study of monogamous, heterosexual, HIV-1-discordant couples in Uganda found that the "overall, unadjusted probability of HIV-1 transmission per coital act is 0·0011...higher viral load and genital ulceration are the main determinants of HIV-1 transmission."[14]

Diagnosis

HIV Test

For more information, see: HIV test.


Other tests

Total lymphocyte count

For more information, see: Lymphocyte count.

In predicting a CD4 lymphocyte count of less than 200:[15]

  • Total lymphocyte count of more than 2000 has sensitivity or 95%
  • Total lymphocyte count of less than 1200 has specificity of 95%

Management

Clinical practice guidelines by the National Institutes of Health[16][17] World Health Organization[18], International AIDS Society – USA[19], and Infectious Diseases Society of America[20] The following should be done when health care is started:[20].

  • CD4 lymphocyte count and percentage
  • Genotype determination to detect resistance
  • Glucose‐6‐phosphate dehydrogenase in certain ethnic groups
  • "Cytomegalovirus (CMV) screening for patients at low risk for CMV infection; varicella zoster virus screening for those who deny history of chickenpox or shingles; HSV‐2 screening is recommended by some expert"
  • "Hepatitis B surface antigen, antibody to hepatitis B surface antigen or to hepatitis B core antigen, antibody to hepatitis C virus, total hepatitis A antibody"
  • Screening for syphilis; Serologic testing for Toxoplasma gondii
  • Tuberculosis screening

In addition:

  • HLA B*5701 should be tested before using abacavir
  • Tropism testing for X4‐ or dual/mixed‐tropic virus before using the CCR5 receptor antagonist maraviroc

Treatment with antiretroviral therapy (ART) is complicated by issues of poverty and education. In communities with adequate resources, HIV infection is treatable with highly active antiretroviral therapy (HAART). This therapy effectively prevents progression to AIDS in many patients, however there are many side effects to treatment, and resistance is a serious issue.

When to start treatment

The World Health Organization recommends starting treatment when the CD4 lymphocyte count is less than 350/microL.[21][22]

In the United States, the Department of Health and Human Services (DHHS) recommends starting treatment when the CD4 lymphocyte count is less than 500/microL.[23]

Clinical practice guidelines by the International AIDS Society-USA panel recommend treatment if any of the following are true:[24]

  • Symptomatic or complicated HIV or hepatitis
  • CD4 counter < 500
  • CD4 count > 500 if not an elite controller

A meta-analysis[25] of randomized controlled trials found two trials[26] and concluded, " initiating ART at CD4 levels higher than 200 or 250 cells/microL reduces mortality rates in asymptomatic, ART-naive, HIV-infected people." A more recent, though small, trial found similar results.[25]

A meta-analysis of cohort studies concludes "350 cells per microL should be the minimum threshold."[27] A more recent cohort study suggests treatment should begin before CD4 lymphocyte count drops to 500/microL.[28]

Available Anti-Retroviral Agents

Anti-Retroviral Agents in bold are recommended initial treatments by AIDSinfo.[29]

Integrase strand transfer inhibitor;s (INSTI)

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

Nucleoside

  • Abacavir (ABC)
  • Didanosine (ddI)
  • Emtricitabine (FTC)
  • Entecavir (ETV)
  • Lamivudine (3TC)
  • Stavudine (d4T)
  • Zalcitabine (ddC)
  • Zidovudine (AZT)

Nucleotide

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

  • Delavirdine
  • Efavirenz (EFV)
  • Etravirine (ETR; TMC125)
  • Nevirapine (NVP)
  • Rilpivirine (RPV)

Protease inhibitors (PIs)

When combined with at least two other drugs, usually NRTs, this combination is called highly active antiretroviral therapy.

  • Amprenavir
  • Atazanavir (ATV). Boosted with ritonavir as ATV/r
  • Darunavir (DRV). Boosted with ritonavir as DRV/r
  • Fosamprenavir
  • Indinavir
  • Lopinavir (LPV; ABT-378). Boosted with ritonavir as LPV/r
  • Nelfinavir
  • Ritonavir
  • Saquinavir
  • Simeprevir(;TMC435)
  • Tipranavir

Inhibitors of cell entry/fusion

HIV fusion inhibitors binds to HIV gp41

Human chemokine receptor 5 (CCR5) blockers bind to the human CCR5 receptor which prevents R5 tropic HIV from entering cells.

Prognosis

A multinational cohort study has found that since the introduction of highly active antiretroviral therapy, "mortality rates for HIV-infected persons have become much closer to general mortality rates." [33]

A second, industry-funded, multinational cohort study has found that with combination treatment, "the average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries."[34]

Screening

For more information, see: HIV screening.


Prevention

Prevention is an issue complicated by issues of poverty and education. Sexual transmission can be effectively prevented by avoiding sexual contact (abstinence), but much of HIV transmission takes place in marriages or other similar relationships, therefore abstinence is impractical. The most effective method is regular, proper use of latex condoms. A large percentage of those infected are unaware of their disease status, which complicates prevention. Spouses are often infected without their knowledge of their partner's status.

Occupational infection can be prevented with the use of universal precautions and by post-exposure prophylaxis.

Currently, no vaccine is available, and it is not clear if a vaccine will be available any time in the near future.

Medications

Randomized controlled trials of prevention of HIV-1 infection.[35][36][37][38][39] [40]
Trial Patients Intervention Comparison Outcome Results Comment
Intervention Control
VOICE[35]
Not published
HIV-1-seronegative female sexual partners of HIV-1-seropositive patients
South Africa, Uganda and Zimbabwe
• TDF (vaginal)
• TDF (oral)
• TDF–FTC (oral)
Placebo HIV-1 infections (any)     Tenofovir stopped due to lack of efficacy
FEM-PrEP Study[36]
2012
HIV-1-seronegative female sexual partners of HIV-1-seropositive patients
13% report transactional sex
Kenya, South Africa, and Tanzania
TDF-FTC Placebo HIV-1 infections (any) over approximately 3 years 4.7 per 100 person-years 5.0 per 100 person-years Ineffective
Partners PrEP Study Team[37]
2012
HIV-1-seronegative sexual partners of HIV-1-seropositive patients
CD$ count of infected partner = 494
Kenya and Uganda
• TDF-FTC or
• TDF
Placebo HIV-1 infection (any) over 3 years • 0.50 per 100 person-years
• 0.65 per 100 person-years
1.99 per 100 person-years • RRR = 75%
• RRR = 67%
Both regimens were effective
TDF2 Study[38]
2012
HIV-1-seronegative adults
Botswana
TDF-FTC Placebo HIV-1 infection (any) over 1.1 years 1.2 per 100 person-years 3.1 per 100 person-years

RRR = 67%
Effective

iPrEx Study[39]
2012
HIV-1-seronegative male sexual partners of HIV-1-seropositive males
41% report transactional sex
6 countries in 4 continents
TDF-FTC Placebo HIV-1 infection (any) ver 1.2 years 3.1 per 100 person-years (estimated; not in original publication) 4.3 per 100 person-years (estimated; not in original publication) RRR = 44%
Effective
HPTN 052 Study[40]
2011
HIV-1-seropositive sexual partner of HIV-1-serodiscordant couple
9 countries in 4 continents
• CD4 counts between 350 and 550 cells per cubic millimete
Early therapy (antiretroviral therapy either immediately) Delayed therapy (after a decline in the CD4 count or the onset of HIV-1-related symptoms) • HIV-1 infection (any)
• HIV-1 infection virologically linked to the infected partner
• 0.3 per 100 person-years
• 0.1 per 100 person-years
• 2.2 per 100 person-years
• 1.7 per 100 person-years
• RRR = 89%
• RRR = 96%
Effective

Prevention in health care settings

For more information, see: Universal precautions.


The United States Centers for Disease Control and Prevention has summarized the use of universal precautions to prevent the transmission of HIV in health care settings.

In addition, the Centers for Disease Control and Prevention has published guidelines on preventing transmission by use of postexposure prophylaxis.[41]

References

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