Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary

Plasma HIV-1 RNA (Viral Load) and CD4 Count Monitoring

Last Updated: May 1, 2014

Recommendations on the Indications and Frequency of Viral Load and

CD4 Count Monitoring

Clinical Scenario	Viral Load Monitoring	CD4 Count Monitoring
Before initiating ART	At entry into care (AIII) If ART initiation is deferred, repeat before initiating ART (AIII). In patients not initiating ART, repeat testing is optional (CIII).	At entry into care (AI) If ART is deferred, every 3 to 6 months^b (AIII)
After initiating ART	Preferably within 2 to 4 weeks (and no later than 8 weeks) after initiation of ART (AIII); thereafter, every 4 to 8 weeks until viral load is suppressed (BIII).	3 months after initiation of ART (AIII)
After modifying ART because of drug toxicities or for regimen simplification in a patient with viral suppression	4 to 8 weeks after modification of ART to confirm effectiveness of new regimen (AIII).	Monitor according to prior CD4 count and duration on ART, as outlined below.
After modifying ART because of virologic failure	Preferably within 2 to 4 weeks (and no later than 8 weeks) after modification (AIII); thereafter, every 4 to 8 weeks until viral load is suppressed (BIII). If viral suppression is not possible, repeat viral load every 3 months or more frequently if indicated (AIII).	Every 3 to 6 months (AI)
During the first 2 years of ART	Every 3 to 4 months (AIII)	Every 3 to 6 months^a (BII)
After 2 years of ART (VL consistently suppressed, CD4 consistently 300-500 cells/mm³)	Can extend to every 6 months for patients with consistent viral suppression for ≥2 years (AIII).	Every 12 months (BII)
After 2 years of ART (VL consistently suppressed, CD4 consistently >500 cells/mm³)		Optional (CIII)
While on ART with detectable viremia (VL repeatedly >200 copies/mL)	Every 3 months (AIII) or more frequently if clinically indicated (see Virologic Failure).	Every 3 to 6 months (AIII)
Change in clinical status (e.g., new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy)	Every 3 months (AIII)	Perform CD4 count and repeat as clinically indicated^c (AIII)
^a Monitoring of lymphocyte subsets other than CD4 (e.g., CD8, CD19) has not proven clinically useful, adds to costs, and is not routinely recommended (BIII). ^b Some experts may repeat CD4 count every 3 months in patients with low baseline CD4 count (<200–300 cells/mm³) before ART but every 6 months in those who initiated ART at higher CD4 cell count (e.g., >300 cells/mm³). ^c The following are examples of clinically indicated scenarios: changes in a patient’s clinical status that may decrease CD4 count and thus prompt initiation of prophylaxis for opportunistic infections (OI), such as new HIV-associated symptoms, or initiation of treatment with medications which are known to reduce CD4 cell count.

AU comment: Guidance for management of low level viraemia (LLV) using the Roche COBAS 6800 testing platform

Updated: November 2020

The accurate quantitation of HIV viral loads is essential in the management of people with HIV infection (PWH). In Australasia, some examples of platforms that are currently in use for measurement of HIV-1 viral load includes the COBASÒ Ampliprep/COBASÒ TaqmanÒ (CAP/CTM) (Roche Diagnostics), PantherÒ (Hologic) and m2000 RealTime System (Abbott). The corresponding assays used to measure HIV viral load by the three platforms are RocheÒ COBASÒ HIV-1, Aptima HIV-1 Quant Dx and Abbott RealTime HIV-1 respectively.

The CAP/CTM platform is expected to be discontinued by the end 2022, and some laboratories may choose to continue testing using the COBASÒ 6800 platform. However, evaluations of the COBASÒ 6800 against other platforms have shown that it may detect the presence of low level HIV-1 viremia (LLV) in samples that previously returned undetectable viral loads using other platforms, including the CAP/CTM (Figure 1). Typically, these are samples in the range of 50 – 200 copies/mL.

The difference in performance of the platforms may be due to the different targets employed in each assay. For example the CAP/CTM, Abbott m2000 and Hologic systems use different targets to detect HIV RNA. Furthermore, the COBASÒ 6800 HIV-1 assay is more accurate and precise, especially at the lower end of detection due to the enhanced extraction and detection technology. Due to the enhanced sensitivity, laboratory specimen processing is important to ensure that HIV DNA from white blood cells is not included.

Clinicians should be aware of the differences of the COBASÒ 6800 platform when managing HIV-1 infected persons, particularly those with low level viremia. Routine assessment of PWH receiving ART includes assessment of adherence, potential drug-drug interactions and the impact of any other intercurrent infections. For people with viral loads below 200 copies/mL and no concerns for virological failure after clinical assessment then repeat testing at earlier intervals than routinely recommended (2) is not necessary

Individuals with viral loads above 200 copies/mL may be at increased risk of virologic failure so repeat viral load testing is indicated (3), preferably within 2 to 4 weeks and no later than 8 weeks. The risk of virologic failure with drug resistance however is more likely if viral load on ART is > 500 copies/mL. Individuals with virologic failure require testing for HIV drug resistance mutations and potentially switching of antiretrovirals if resistance is detected to antiretrovirals they are receiving.

It should also be noted that evidence from the trials reporting that suppressed HIV viral load on ART effectively reduces the risk of HIV transmission to zero used a definition that HIV viral load was < 200 copies/mL. on ART. Therefore HIV viral load results < 200 copies/mL on ART is what is needed to meet the requirements of “Undetectable = Untransmittable”

Figure 1a. Whisker plots demonstrating assay accuracy for replicates of different HIV-1 subtypes at 50 copies/mL when measured by the COBASÒ HIV-1, Aptima HIV-1 Quant Dx and RealTime HIV-1 Quant Dx assays

Figure 1b. The range of uncertainty for replicates of different HIV-1 subtypes at 50 copies/mL when measured by the COBASÒ HIV-1, Aptima HIV-1 Quant Dx and RealTime HIV-1 Quant Dx assays. The diamonds represent assay-specific values and the white bars around the diamond represent the range of uncertainty of each assay’s results

References

Wiesmann F, Ehret R, Naeth G, et al. Multicenter evaluation of two next-generation HIV-1 quantitation assays, Aptima Quant Dx and Cobas 6800, in comparison to the RealTime HIV-1 reference assay. J Clin Microbiol 2018; 56: pii: e00292-18. doi: 10.1128/JCM.00292-18.
S DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Plasma HIV-1 RNA (Viral Load) and CD4 Count Monitoring https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/458/plasma-hiv-1-rna--viral-load--and-cd4-count-monitoring
S DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV Management of the Treatment-Experienced Patient. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/15/virologic-failure