Update on antiretroviral treatment during primary HIV infection

Abstract

Primary HIV-1 infection covers a period of around 12 weeks in which the virus disseminates from the initial site of infection into different tissues and organs. In this phase, viremia is very high and transmission of HIV is an important issue. Most guidelines recommend antiretroviral treatment in patients who are symptomatic, although the indication for treatment remains inconclusive in asymptomatic patients. In this article the authors review the main virological and immunological events during this early phase of infection, and discuss the arguments for and against antiretroviral treatment. Recommendations of different guidelines, the issue of the HIV transmission and transmission of resistance to antiretroviral drugs, as well as recently available information opening perspectives for functional cure in patients treated in very early steps of HIV infection are also discussed.

Keywords::

• acute retroviral syndrome
• antiretroviral treatment
• eradication
• Fiebig phases
• functional cure
• HIV guidelines
• HIV infection
• primary HIV infection
• therapeutic vaccines
• transmitted drug resistance

Acknowledgements

Juan Ambrosioni developed this work in the frame of a ‘Juan de la Cierva 2012’ post-doctoral program, Ministerio de Competitividad, Spain. This work was the basis for the request of a post-residency Scholarship Ajuts a la Recerca ‘Josep Font’ 2014, Hospital Clinic, Barcelona, Spain, attributed to David Nicolas.

Financial & competing interests disclosure

This review was supported in part by grants from the Spanish Foundation for AIDS Research and Prevention (Madrid, Spain) FIPSE grant 00/3128, the “Instituto de Salud Carlos III – Fondo de Investigaciones Sanitarias” (Madrid, Spain) FIS grant PI 040363 and the Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Primary HIV infection (PHI) covers the period of around 12 weeks post-HIV-1 infection. Acute infection is that of less than 1 month (pre-serologic period) and recent infection is that of less than 6 or 12 months.

• Depletion of lymphoid tissue and establishment of viral reservoir occurs early on in this period.

• Patients with PHI are a significant source of HIV transmission, due particularly to the high viral load, highlighting the need for earlier diagnosis. In around 10% of cases, transmission of resistance to antiretrovirals (ARV) can occur.

• Guidelines uniformly recommend treatment for symptomatic patients; recommendation remains inconclusive for asymptomatic patients.

• No ARV regimen for treatment of PHI (non-nucleoside reverse-transcriptase inhibitor-, ritonavir-boosted protease inhibitor- and integrase inhibitor-based regimen) is preferred, but an integrase inhibitor regimen can decrease the viral load and transmissibility more quickly. If resistance tests are unavailable, a ritonavir-boosted protease inhibitor may be preferred until results are available.

• Recent cases of patients treated very early with subsequent control of the viral replication after withdrawal of ARV open the possibility of a functional cure.

Notes