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Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
Published on: September 26, 2011
Interpretation of indeterminate HIV-1 PCR results are influenced by changing vertical transmission prevention
Jean Maritz1, Jayshree Narvin Maharaj1, Mark Frederic Cotton2
1Division of Medical Virology, Department of Pathology, National Health Laboratory Service and Stellenbosch University, Cape Town, South Africa.
Insights
Indeterminate HIV PCR results in infants are decreasing with Option B+ regimens but still indicate a high likelihood of infection. Further virological testing is crucial for definitive diagnosis in HIV-exposed infants.
Area of Science:
- Pediatric infectious diseases
- Virology
- Public health
Background:
- Antiretroviral drug suppression of HIV can lead to indeterminate PCR results in infants.
- This diagnostic challenge complicates early identification and treatment initiation for infected infants.
- The impact of different vertical HIV transmission prevention (VTP) regimens on indeterminate PCR rates and predictive value is unclear.
Purpose of the Study:
- To examine indeterminate PCR rates and outcomes in HIV-exposed infants under intensified VTP in South Africa.
- To assess the predictive value of indeterminate PCR for later positive results.
- To analyze the influence of VTP regimens on PCR results.
Main Methods:
- Retrospective analysis of diagnostic PCR data from a public health laboratory (2009-2014).
- Categorization of results by South African VTP regimens.
- Linking initial indeterminate PCRs in infants (<12 months) with follow-up PCRs and serological tests.
Main Results:
- Intensified VTP regimens significantly reduced indeterminate (5.6% to 3.2%) and positive (2.4% to 0.4%) PCR rates (p<0.001).
- Under WHO Option B+, 64.1% of indeterminate results were followed by positive PCRs, compared to 14.7% with older regimens (p<0.001).
- These positive follow-up results occurred at a median of 28 days.
Conclusions:
- Indeterminate HIV PCRs are decreasing with Option B+ but remain highly suspicious for true HIV-1 infection.
- Indeterminate results necessitate further virological testing for definitive diagnosis in HIV-exposed infants.
- VTP regimen choice impacts the frequency and predictive value of indeterminate PCR results.
Background:
Suppression of HIV by antiretroviral drugs may be one of the reasons that indeterminate HIV-1 PCR results are obtained from testing HIV-exposed infants. This complicates the early identification of infected infants, potentially delaying initiating treatment early. There is uncertainty as to how different vertical HIV transmission prevention regimens (VTP) affect the rate and predictive value of indeterminate PCR results.
Objectives:
To investigate rates of indeterminate PCR results, outcomes of subsequent samples and the predictive value of an indeterminate PCR for a later positive result in the setting of intensifying VTP in the Western Cape province of South Africa.
Study Design:
Retrospective laboratory data analysis. Diagnostic PCR data of a public health laboratory from June 2009 to October 2014 was analysed and categorised by South African VTP regimens. First indeterminate HIV-1 PCRs in patients younger than 12 months were linked with follow-up HIV-1 PCRs and/or serological tests. Linked results sets were analysed by PCR amplification characteristics and subsequent patient outcome.
Results:
Over intensified VTP regimens, the rate of indeterminate and positive PCRs decreased significantly (5.6-3.2% and 2.4-0.4%, respectively; both p<0.001). Most notably, significantly more patients with indeterminate results had positive PCRs on subsequent samples during WHO Option B+ use compared to older regimens (64.1% vs. 14.7%, p<0.001) at a median 28days later.
Conclusions:
Indeterminate HIV PCRs, although decreasing in frequency with Option B+, should be regarded with a high index of suspicion for being representative of true HIV-1 infections. Additional virological testing is required to arrive at a definitive diagnosis.
