Human immunodeficiency virus and acquired immunodeficiency syndrome

Human immunodeficiency virus (HIV) is a retrovirus which causes HIV infection. If left untreated, it will lead to acquired immunodeficiency syndrome (AIDS), a condition characterised by a CD4+ T-cell count of < 200/µL and/or the presence of so-called AIDS-defining condition, whichever occurs first.

38 million people worldwide live with AIDS, and every year around 1,7 million people are infected. 60% of new cases are in sub-Saharan Africa.

With proper lifelong modern treatment, people with HIV can live normal lives and have a zero risk of developing AIDS. Unfortunately, most people who are affected by HIV do not have access to modern treatment.

Etiology

Risk factors

• Men who have sex with men
• Intravenous drug needle sharing
• Blood transfusion
  • Nowadays very uncommon (1 in 2 million)
  • Screening for it began in the 1990s

The virus can also be transmitted vertically, during vaginal birth, intrauterine life, or during breastfeeding. In an untreated mother, the risk of transmission to the child is around 1:3.

According to the CDC, the risk of acquiring HIV from an infected source per single act is relatively low:

Type of exposure	Risk per exposure
Blood transfusion with infected blood	92,5%
Needle-Sharing During Injection Drug Use	0,63%
Receptive Anal Intercourse	1,38%
Insertive Anal Intercourse	0,11%
Receptive Penile-Vaginal Intercourse	0,08%
Insertive Penile-Vaginal Intercourse	0,04%
Receptive Oral Intercourse	Low
Insertive Oral Intercourse	Low

Pathomechanism

The virus has many components, the most important of which are the glycoprotein 120 and 41 (gp120 and gp41), as these glycoproteins are involved in the entry of the virus into the CD4+ T-cell. The virus enters the cell by binding to the CD4 receptor and either CCR5 or CXCR4 coreceptor.

Clinical features

At around week 5 after the primary infection, acute HIV syndrome occurs with non-specific symptoms like fever, fatigue, rashes, headache, lymphadenopathy. It may be symptomatic. This lasts for 1 – 2 weeks.

After the acute HIV syndrome, a clinical latent period occurs, as the patient remains asymptomatic for 3 – 4 years, until the CD4+ T-cell count reaches around 200-300/µL. At that point the CD4+ count is so low that opportunistic infections and neoplasms occur. These are the so-called AIDS-defining conditions, and include:

• Kaposi sarcoma
• Tuberculosis
• Pneumocystis jirovecii pneumonia (PCP)
• Cryptococcus pneumonia
• Candida oesophagitis
• Toxoplasma brain abscess
• CMV retinitis
• Non-Hodgkin lymphoma

In addition to these, other opportunistic conditions can occur:

• Herpes zoster
• Oral hairy leukoplacia
• Oral candidiasis
• Molluscum contagiosum

Diagnosis and evaluation

Quick tests which detect both anti-HIV antibodies and the p24 protein of the virus in blood or urine can be used to screen for HIV in 5 – 10 minutes. However, the diagnosis must be confirmed by western blot.

In all who are diagnosed with HIV, the viral load (the amount of HIV RNA) in the blood as well as the CD4+ T-cell count should be measured.

People at risk should be screened regularly.

Treatment

There are many drugs used in the treatment of HIV. According to the lecturer in infectology, it’s not necessary to know the name of the drugs for the infectiology exam, and I doubt they’ll ask for it on the final as well. Anyway, these are some of the most frequently used ones nowadays:

• Nucleoside reverse transcriptase inhibitor (NRTI)
  • Emtricitabine (FTC)
  • Abacavir (ABC)
  • Lamivudine (3TC)
  • Zidovudine (AZT)
• Non-nucleoside reverse transcriptase inhibitor (NNRTI)
  • Rilpirivin (RPV)
  • Delavirdine (DLV)
  • Etravirine
  • Efavirenz
• Nucleotide analogues
  • Tenofovir (TDF)
• Protease inhibitors (PI)
  • Darunavir (DRV)
  • Atazanavir
• Fusion inhibitors
  • Enfuvirtide
  • Maraviroc
• Integrase strand transfer inhibitors (INSTI)
  • Raltegravir (RAL)
  • Dolutegravir (DTG)

The standard of care for HIV treatment is highly active anti-retroviral therapy (HAART), which includes a combination of 3 antiretroviral drugs in one of these three options:

• 2 NRTIs + 1 INSTIs
• 2 NRTIs + 1 NNRTIs
• 2 NRTIs + 1 PIs

It’s important to take the drugs correctly. They must be taken every day, 1 – 4 times a day, at exactly the same time to prevent development of resistance. Sometimes patients are advised to do a “trial run” where they try to take a placebo (or a vitamin pill or a jellybean) at the exact same time every day, as if they were medicine, to check whether they can adhere to the regimen. Missing a few doses in a row can lead to resistance.

It’s advised to start HAART as soon as HIV is diagnosed, as soon as the patient is ready to adhere to the regimen. Initiating treatment in a patient who is not ready leads to resistance and will cause problems later.

With good adherence to HAART, the viral load can be reduced to undetectable levels, and the CD4+ T-cell count can be kept at a normal level. At this point, the risk of infecting anyone with HIV is effectively zero, and the risk of progression is very low as long as adherence to HAART is maintained. If progression occurs, the HAART combination must be changed.

AIDS-defining conditions must be treated appropriately. HAART is also important to treat and prevent these conditions.