Treatment of HIV-infection

Acute HIV infection

Epidemiology

Acute HIV Infection (also called Primary HIV-infection) encompasses the first 3 to 6 months after infection. Scientific data demonstrate that acute HIV Infection accounts for approximately 40 percent of onward transmissions. Therefore, the detection and early treatment of acute HIV infection plays an important role also from a public health perspective and early initiation of antiretroviral therapy at the time of infection is an effective measure to reduce the transmission rate on a population level. Therefore, it is crucial to offer and perform HIV testing in people belonging to risk groups (e.g., men who have sex with men) and people who practice sexual risk behavior.

Symptoms

The acute HIV Infection presents symptomatically as a flu-like syndrome in approximately 70 percent of all cases. Symptoms and signs occurring after infection are often referred to as acute retroviral syndrome. The most common symptoms and signs include fever, malaise, sore throat, skin rash and lymphadenopathy (see table 1). However, the unspecific nature of these signs and symptoms preclude a reliable clinical diagnosis. In one third of cases acute HIV Infection presents without symptoms, with a single symptom only or with unexpected symptoms and signs.

Table 1: Symptoms and signs of 290 patients with an acute HIV Infection from the Zurich Primary HIV Infection Study (Braun et al, Clinical Infectious Diseases, 2015).

Diagnostics

For HIV screening combined tests (so called Combo tests) are used which detect both HIV antibody against HIV-1 and HIV-2, and HIV-1 p24 antigen, The routine 4th generation Combo test detects acute HIV infection in most cases within two to three weeks after infection and should be used for screening. A HIV-infection is ruled out if the 4^th generation Combo test turns out negative at least six weeks after a risk situation. If positive the screening test needs to be confirmed by another test from a different blood sample. A routine use of the HIV-specific PCR for screening purposes is discouraged. If the HIV screening test turns out negative but the clinical suspicion for acute HIV infection remains high, the HIV test should be repeated again one to two weeks later.

Therapy

During the last decade early antiretroviral therapy has been clearly recognized as beneficial for patients with acute HIV infection and therefore is recommended by all international expert panels. It has been shown that early antiretroviral treatment leads to a significant reduced latent viral reservoir compared to patients starting treatment during chronic phase, enhances CD4 cell count recovery and prevents transmission. Early antiretroviral therapy consists of the same drugs as recommended for chronically infected patients. Early antiretroviral treatment should be initiated in the setting of physicians working in the field of HIV, e.g. within the Zurich Primary HIV Infection Study of the University Hospital Zurich.

Cooperation

• http://www.viralinfectiousdiseases.uzh.ch/ZPHI.html

Chronic HIV infection

Epidemiology

In 2015 there were about 37 million people living with HIV worldwide, 69% of them in sub-Sahara Africa. There were 2 million people newly infected with HIV this year, 95% of them in countries with low or middle-income and 1.2 million people died as a result of HIV and AIDS. The Federal Office of Public Health (BAG) estimates that in Switzerland 13,000 – 20,000 people are living with HIV/AIDS.This results in a prevalence of 2.7 – 3.6 per 1000 people. The prevalence of the BAG is similar to calculations of the Swiss HIV Cohort Study (SHCS) which estimates the number of HIV infected individuals living in Switzerland of about 15’000-20’000 (Kohler et al, AIDS, 2015).

Symptoms

There are no symptoms or signs that might diagnose or exclude a HIV infection for sure. Persons who become newly infected with HIV present symptomatically in approximately two third of cases with an acute retroviral syndrome, which is commonly described as flu-like syndrome and varies with regard to  intensity and duration (see also the acute HIV infection. Since the symptoms of a HIV infection can be very unspecific both in the acute and in the chronic phase and the acute HIV infection may present with atypical or unexpected symptoms in up to one third of cases, the diagnosis is often missed early on after infection. It is therefore essential to think even in the absence of a classical acute retroviral syndrome or atypical symptoms of a HIV infection, in particular when the history (e.g., previous sexual risk contacts) or belonging to a risk group (e.g., men who have sex with men, multiple sexual partners) are indicative. In this case, an HIV test should be made with a low threshold.

Diagnostics

For HIV screening combined tests (so called Combo tests) are used which detect both HIV antibody against HIV-1 and HIV-2, and HIV-1 p24 antigen. In half of newly infected patients the combined tests become reactive within about 16 days after infection. However, in the other half it may takes longer. Therefore, it is still considered that HIV infection can only be ruled out by a negative 4^th generation HIV Combo test six weeks after exposure to HIV. In extremely anxious people and in people who demonstrably had sexual contact with untreated HIV-infected individuals, an HIV test can at best make sense already four weeks after risk contact. However, a negative test is not conclusive at this time to prove the status of “HIV-negative”. A final test is indicated six weeks after potential risk situations. Combo tests are also available as rapid tests for walk-in clinics and STI clinics. However, the sensitivity of rapid tests is significantly less than the sensitivity of the laboratory tests in patients with acute HIV infection and therefore is not recommended for this situation.

Therapy

The success of antiretroviral therapy to HIV-1 is unique in the modern medicine history. A previously almost 100% fatal disease could be turned into a chronic treatable disease. If nowadays antiretroviral therapy is started early according to international recommendations, the negative effects of HIV-1 on the human organism can be minimized. This results in otherwise healthy HIV-infected people in an  normal life expectancy. In addition, patients with successful treatment are no longer infectious, which is crucial for curbing the pandemic. The International Antiviral Society-USA (IAS-USA) recommends in its the latest version of  Guidelines that antiretroviral therapy (ART) should be offered to all HIV-infected patients, regardless of their CD4 cell counts. This recommendation is based on the results of data from cohort studies, which showed that the benefit of treatment clearly overweigh the risks today. Other guideline panels such as the WHO and the DHHS have also adapted this strategy in particular after the START trial was published in 2015. Since ART is also a highly effective element of prevention, it makes sense to treat as many patients as possible. For the prevention of drug resistance and improvement of effectiveness ART is mostly prescribed as a combination of different classes of substances. Which combination is used is a complex decision that must be based on the treatment history of the patient, resistance testing, side effect profile, comorbidities, and drug interactions.

Cooperation

• www.europeanaidsclinicalsociety.org
• www.iasusa.org/
• www.shcs.ch