HIV RNA Assays
Patients initiating antiretroviral therapy or starting a new regimen should undergo close virologic monitoring to evaluate the response to therapy. In the United States, multiple nucleic acid-based tests are available for the measurement of HIV-1 RNA levels. The HIV RNA assays are typically categorized into one of the following methods: polymerase chain reaction (PCR), reverse transcription polymerase chain reaction (RT-PCR), or nucleic acid sequence-based amplification (NASBA). The HIV RNA assays used for monitoring response to therapy typically have a HIV RNA detection threshold of 20 to 75 copies/ml. "Real time" assays have provided an advantages in HIV monitoring via a more rapid turnaround for results. Given that significant interassay variability can occur, the same assay should ideally be used when following virologic trends and responses to antiretroviral therapy in an individual patient.
HIV RNA Monitoring
The 2014 United States HHS antiretroviral therapy guidelines recommend that patients should have a baseline plasma HIV RNA level checked before initiating, modifying, or changing antiretroviral therapy. After starting a new regimen, the HIV RNA level should be checked in 2 to 8 weeks (preferably in 2 to 4 weeks) after starting therapy and the HIV RNA level should substantially decrease within 4 weeks (at least a 1.0 log decrease compared with baseline). Factors that can potentially impact the initial HIV RNA response include poor medication adherence, preexisting antiretroviral resistance, baseline HIV RNA levels, regimen potency, medication absorption, and drug-drug interactions. After the initial post-treatment HIV RNA level, the patient should have repeat HIV RNA testing every 4 to 8 weeks until the HIV RNA level becomes undetectable (less than 20 to 75 copies/ml). Most patients have a rapid decline in HIV RNA levels and attain an undetectable HIV RNA level within 8 to 24 weeks (Figure 1), but in some instances, particularly with very high baseline HIV RNA level, the time to achieve an undetectable HIV RNA level may exceed 24 weeks. With a delayed response, it is important to continue close monitoring to ensure that HIV RNA levels continue to decline. Once the HIV RNA becomes undetectable, monitoring frequency can decrease to every 3 to 4 months. For adherent patients who have undetectable HIV RNA levels for at least 2 years and are clinically and immunologically stable, monitor intervals can extend every 6 months. The following three circumstances may indicate virologic failure and a need to perform resistance testing: (1) the HIV RNA remains detectable 24 weeks after starting therapy and is no longer declining (Figure 2), (2) the HIV RNA level initially decreases, but then increases compared with the previous value (Figure 3), and (3) the patient has a significant and persistent increase in HIV RNA levels after a period of sustained optimal HIV RNA suppression (Figure 4). In each of these three circumstances, resistance testing is ideally performed, unless the HIV RNA levels are too low to reliably perform the resistance test.
CD4 Cell Count Monitoring
In the first 6 months after starting antiretroviral therapy, HIV RNA responses are much more important to follow than CD4 responses. The early post change CD4 count responses vary widely and can provide misleading information for the patient. Frequent and intense CD4 count monitoring after starting a new regimen or changing a regimen is not recommended. Further, CD4 count changes as an indicator of antiretroviral failure typically lags far behind changes in HIV RNA levels. Most patients will have an increase in CD4 cell count by 100 to 150 cells/mm3 within 1 year after starting antiretroviral.[,] The CD4 cell count monitoring is the same regardless of the regimen used. Patients initiating antiretroviral therapy should have a baseline CD4 cell, a repeat CD4 cell count 3 months after starting therapy, and then every 3 to 6 months for the first 2 years after starting therapy. After the first 2 years, patients who maintain an undetectable HIV RNA value and have a CD4 cell count consistently in the range of 300 to 500 cells/mm3 for at least 2 years can extend the CD4 monitoring interval to every 12 months. For those patients who have a CD4 count greater than 500 cells/mm3 for at least 2 years, monitoring of CD4 cell counts is considered optional.[,,] Although relatively infrequent, some patients have an excellent virologic response, but have minimal CD4 cell count increases, or in some instances, actually have a decline in CD4 cell count. These responses characterized by good HIV RNA responses and poor CD4 cell count responses are often referred to as "discordant responses". The reason for a discordant response is usually not clear, but the poor CD4 cell count response does not indicate a treatment failure. The topic of discordant CD4 and HIV RNA responses is discussed in detail in the case Discordant CD4 Cell Count and Viral Load Responses to Antiretroviral Therapy.
Laboratory Monitoring for Antiretroviral Toxicity
Patients on antiretroviral therapy can develop drug toxicity and monitoring of certain laboratory values is recommended to minimize the risk of toxicity[,]; the HHS 2014 antiretroviral therapy guidelines provide specific recommendations for laboratory monitoring for patients taking antiretroviral therapy (Figure 5). Routine monitoring of serum lactate is not recommended, regardless of the regimen the patient is taking. Patients should have a baseline fasting lipid panel that includes total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides, and these studies should be repeated every 6 months if abnormal or every 12 months if normal. A fasting glucose is recommended prior to starting therapy, and if the level should be repeated every 6 to 12 months depending on whether the prior value was normal. Routine glucose tolerance testing is not recommended. All of the currently marketed non-nucleoside reverse transcriptase inhibitors and protease inhibitors have been associated with potential increases in serum aminotransferase levels. Accordingly, the HHS antiretroviral guidelines recommend monitoring alanine aminotransferase (ALT), aspartate aminotransferase (ALT), and total bilirubin levels every 3 to 6 months. Among the antiretroviral medications, nevirapine (Viramune) poses the greatest risk of developing clinical hepatitis. If a patient starts a regimen that includes nevirapine, hepatic aminotransferase values should be checked at baseline and at 2 and 4 weeks after starting nevirapine. For all patients, routine monitoring of renal function is recommended every 3 to 6 months and patients receiving tenofovir (Viread) should have a urinalysis checked every 6 months.[,]