Could an elevated viral load on a Zidovudine (ZDV), Lamivudine (3TC), and Nevirapine (NVP) regimen be a transient blip?

Viral Load Blips on ZDV/3TC/NVP Regimen

Yes, an elevated viral load on a ZDV/3TC/NVP regimen can be a transient blip, but this requires careful interpretation because blips on NNRTI-based regimens may be associated with drug resistance mutations, particularly the M184V mutation affecting lamivudine. 1

Definition of Viral Blip

A virological blip is defined as an isolated increase in HIV RNA levels to <1000 copies/mL with a return to undetectable levels while receiving ART, and is rarely associated with progression to virological failure. 1

• Switching ART in the setting of a blip is not recommended. 1
• Virological failure, in contrast, requires a confirmed HIV RNA level above 200 copies/mL on 2 consecutive measurements. 1

Critical Consideration: Drug Resistance During Blips

The key concern with blips on your ZDV/3TC/NVP regimen is that research demonstrates blips can be associated with emergence of drug resistance mutations, even when they resolve spontaneously:

• In one study of patients on HAART containing lamivudine, 8 of 11 patients with blips (median viral load 76 copies/mL) had mutations conferring drug resistance, with 6 patients showing the M184V substitution affecting lamivudine. 2
• Despite these resistance mutations, plasma HIV RNA levels remained undetectable in 13 of 15 patients during a median 27-month follow-up. 2
• Another study found that new drug resistance mutations in either reverse transcriptase or protease genes emerged in 6 of 7 patients during blips, yet none showed virological failure during median follow-up of 120 weeks. 3

Clinical Management Algorithm

For a single blip <1000 copies/mL:

1. Do not switch therapy immediately. 1
2. Assess adherence rigorously - poor adherence is the most common cause of temporary viral rebound and can lead to subtherapeutic drug levels allowing viral replication. 1
3. Repeat viral load testing to confirm return to undetectable levels (the defining characteristic of a blip versus true virological failure). 1
4. Consider resistance testing only if:
   • The blip is followed by persistent detectable viremia (>200 copies/mL on consecutive measurements). 1
   • There is a pattern of increasing viral loads rather than return to suppression. 1
   • Clinical or immunologic deterioration occurs. 1

For confirmed virological failure (HIV RNA >200 copies/mL on 2 consecutive measurements):

• For failure of an NNRTI-based regimen like ZDV/3TC/NVP, dolutegravir plus 1 or 2 active NRTIs is superior to lopinavir plus 2 NRTIs, regardless of the presence of M184V mutation. 1
• Resistance testing should guide the new regimen selection. 1

Important Caveats

• The M184V mutation is found in 80% of patients failing NNRTI-based regimens, making lamivudine resistance common in this setting. 1
• Blips indicate that viral replication may be occurring during HAART, likely caused by temporary decreases in active drug concentrations. 2
• The ZDV/3TC/NVP regimen is no longer a preferred first-line regimen - current guidelines recommend integrase inhibitor-based regimens (dolutegravir or bictegravir) due to superior efficacy, tolerability, and higher genetic barrier to resistance. 4, 5
• If this patient continues on ZDV/3TC/NVP with recurrent blips or any confirmed virological failure, switching to a modern integrase inhibitor-based regimen should be strongly considered. 4, 5