Does Nevirapine Lower Viral Load More than Efavirenz?

		SUMMARY: Among the non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, nevirapine (Viramune) may be able to reduce plasma HIV viral load to a lower level than efavirenz (Sustiva, also in the Truvada and Atripla combination pills), according to a French study described in the December 13, 2010 advance online edition of AIDS. Both drugs suppress virus to undetectable levels using standard tests, but people taking nevirapine were more likely to reach a level below 1 copy/mL.

By Liz Highleyman

All widely used antiretroviral therapy (ART) regimens reduce plasma HIV RNA levels to a so-called "undetectable" level in most patients, typically defined as below 50 copies/mL. But ultra-sensitive viral load tests show that almost all HIV positive people have a low level of residual virus despite treatment.

S. Haim-Boukobza and colleagues from France performed a retrospective analysis to compare levels of residual HIV viremia below 50 copies/mL among patients receiving the NNRTIs nevirapine or efavirenz, both in combination with a NRTI backbone of tenofovir (Viread) plus emtricitabine (Emtriva).

The study included 165 HIV positive participants observed after they had achieved and maintained virological suppression (< 50 copies/mL) for at least 6 months using standard tests. A total of 75 were using nevirapine and 90 were taking efavirenz.

The researchers measured residual plasma viral load using an ultra-sensitive assay with a limit of quantification of 1 copy/mL. They then compared the proportions of patients in the nevirapine and efavirenz groups who suppressed HIV RNA below this level.

Results

	Participants in the nevirapine group had a viral load below 1 copy/mL significantly more often than people in the efavirenz group (81.3 vs 55.6%, respectively; P < 0.001).
	In a multivariate analysis controlling for potential confounding factors, the only factors independently associated with viral suppression below 1 copy/mL were:
	Using nevirapine rather than efavirenz: odds ratio (OR) 2.85 (P = 0.005); Duration of viral suppression on ART: OR 2.07 (P = 0.005).

To explain these findings, the study authors noted that nevirapine has good penetration into anatomic "compartments" that can serve as viral reservoirs, such as the brain and genital tract. Controlling HIV in these compartments may prevent the virus from escaping and starting to replicate in the blood.

However, the investigators cautioned that the clinical relevance of having a viral load below 1 copy/mL is unclear. Further research is needed to determine, for example, how low-level residual virus affects systemic immune activation and inflammation, which have been linked to premature immune system aging and increased risk of non-AIDS conditions such as cardiovascular disease.

Investigator affiliations: Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC Univ Paris, France; Laboratoire de Virologie, AP-HP, CHU Saint Antoine, France; UPMC Univ Paris, France; Service de Maladies Infectieuses, AP-HP, Hopital Saint-Antoine, France; Boehringer Ingelheim, France; Service de Médecine Interne, AP-HP, Groupe Hospitalier Pitié-Salpetrière, Paris, France; Service de Maladies Infectieuses, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; UPMC Univ Paris, INSERM U943, Paris, France.

1/7/11

Reference

S Haim-Boukobza, L Morand-Joubert, P Flandre, and others. Higher efficacy of nevirapine than efavirenz to achieve HIV-1 plasma viral load below 1 copy/ml. AIDS (Abstract). December 13, 2010 (Epub ahead of print).