AIDS (HIV): Drug Therapy

Therapy goals

• Prolongation of survival
• Partner management in the case of a fresh HIV infection, i.e. infected partners, if any, must be located and treated (contacts in the last three months or from the time until the last negative test must be informed).

Therapy recommendations

• The following are the current WHO recommendations:
  • Every HIV-positive person (children and adolescents included) should take antiretroviral drugs from the beginning (regardless of CD4 cell count).
  • HIV-negative partners from serodiscordant couples and men who have sex with men (MSM) should take preexposure prophylaxis, preferably with a combination of tenofovir plus emtricitabine.
• Initial therapy:
  • See below: recommended initial antiretroviral therapy (ART) for patients with HIVa.
• Early antiretroviral therapy (ART) of HIV infection accelerates recovery of immune parameters and may also delay the timing of lifelong therapy in the late phase.
• Multidrug-resistant (MDR) HIV infection: ibalizumab (monoclonal antibody that binds CD4, the primary receptor for HIV, and prevents HIV from entering cells; was the first drug approved for the treatment of MDR HIV in the United States); the agent is administered i.v. in combination with other antiretroviral agents at a dose of 200 mg every 2 weeks; also approved in Europe as of November 2019.
• Regular laboratory checks to verify the success of therapy must be made.
• See also under “Further therapy”.

Recommended initial antiretroviral therapy (ART) for patients with HIVa.

• Bictegravir / tenofoviralafenamide / emtricitabine
• Dolutegravir plus
  • Tenofovirdalafenamide / emtricitabine
  • Tenofovir di-proxil fumarate / emtricitabine
  • Tenofovir di-proxil fumarate / lamivudine
• Dolutegravir / lamivudine with reservedb

Legend

• AListed alphabetically by integrase strand transfer inhibitor (INSTI) component. Drug components separated by a virgule (/) indicate that they are available as co-formulations.
• BNot recommended for rapid start, as initial laboratory results must be verified before initiation. Also not recommended for patients with chronic hepatitis B or HIV RNA above 500,000 copies/mL and possibly a CD4 cell count below 200/μl, although the latter is unclear. Close monitoring for adherence and virologic response is required. Not recommended for patients being treated for active opportunistic infection.

Additional Notes

• The International Antiviral Society-USA (IAS-USA) gives preference to integrase inhibitors (elvitegravir, dolutegravir, raltegravir) for this purpose.
• The randomized START trial was able to show, was therapy initiated at a helper cell count above 500/µl, the risk – for the occurrence of events that define the “acquired immune deficiency syndrome” (AIDS), and also of non-AIDS-defining events – was lower than in patients who received therapy only after helper cells fell below 350/µl.

Pregnancy

Vaginal delivery may be attempted in an HIV-positive pregnant woman under the following conditions:

• Gestational age of at least 37 + 0 SSW.
• Exclusion
  • Obstetric contraindications (e.g., transverse position).
  • Other sexually transmitted infections (STI) requiring treatment.
• HI viral load below the limit of detection at 36 + 0 SSW.

Recommended during pregnancya

• Atazanavir / ritonavirb
• Darunavir / ritonavirb
• Dolutegravirb,c
• Efavirenzb
• Raltegravirb
• Rilpivirind

Legend:

• aListed in alphabetical order. Drug components separated by a virgule (/) indicate that they are available as co-formulations.
• bIn combination with tenofovir di-proxil fumarate/emtricitabine or tenofovir di-proxil fumarate/lamivudine. There are data supporting the use of dolutegravir plus tenofoviralafenamide / emtricitabine during pregnancy.
• CFemales who take this medication when they become pregnant do not necessarily need to change ART.
• dCan be used during pregnancy as part of the treatment plan. Abacavir/lamivudine can be used during pregnancy in place of one of the other components of the two-nucleoside reverse transcription inhibitor, but data and experience for both are more limited.

Antiretroviral drugs

Antiretroviral drugs act against retroviruses, which is a certain subgroup of viruses, which include the viruses responsible for AIDS.The following groups of antiretroviral drugs are distinguished.

• Nucleoside analogues – for example, tenofovir.
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – for example, efavirenz.
• Fusion inhibitors – for example, enfuvirtide.
• Protease inhibitors – for example, atazanavir.
• Integrase inhibitors – for example, elvitegravir, dolutegravir* , raltegravir.
• Reverse transcriptase inhibitors – for example, lamivudine.

Usually, several of the above drugs are combined to achieve the maximum effect. The form of therapy is called HAART therapy (highly active antiretroviral therapy). This therapy cannot cure the affected person, but it can certainly prolong life for many years. * The WHO recommends the integrase inhibitor dolutegravir (DTG) as first-line and second-line therapy of choice for HIV-infected persons, explicitly also for pregnant women and women of childbearing potential on the basis of a new study. According to this study, there is a smaller difference than previously thought, but nevertheless a significant difference in the frequency of neural tube defects in children of HIV-positive women. Further references

• Elvitegravir– and cobicistat-containing drugs: Increased risk of treatment failure and mother-to-child transmission of HIV infection due to lower plasma concentrations in the second and third trimesters of pregnancy.

In addition to therapy for HIV infection, concurrent infection with herpes virus (HSV) should also be treated intensively, according to the latest findings, as studies suggest that HSV therapy also curbs HIV viruses.