Certain Antiretroviral Drugs Have Higher HIV Rebound Rates Than Others in Patients with HIV Viral Loads <50 copies/mL

By Ronald Baker, PhD

Table 1:
Person-years of follow-up (pyrs) and number of virological rebounds according to exposure to nucleoside reverse transcriptase inhibitor (NRTIs).

Table 2:
Person years of follow-up (pyrs) and number of virological rebounds according to exposure to the "third" drug of a 3-drug regimen.

The ultimate goal of HAART is often described as the achievement and maintenance of HIV suppression to undetectable levels, as this results in the greatest potential for immune recovery. For durable results, viral suppression must be maintained, because virologic failure can lead to the development of resistant virus, which in turn often results in immunological decline.

There are scant data available on the use of specific anti-HIV drugs and the rate of viral rebound in individuals on HAART who achieve an HIV viral load < 50 copies m/L.

In the present study, researchers in the United Kingdom Collaborative HIV Cohort (CHIC) Study Group report on the rate of viral rebound associated with different antiretrovirals and whether the length of time that a patient has a suppressed viral load influences their risk of rebound. The researchers explored these issues in a large cohort of HIV patients in the United Kingdom. The results of their work, summarized below, appear in the October 15, 2005 issue of Journal of Infectious Diseases [1].

To be included in the study, individuals were required to be aged >16 years, HIV positive and to have visited at least one of the participating medical centers for care during the period 1996 – present. In addition, all individuals in the CHIC cohort who had attained at least one viral load <50 copies/mL while receiving HAART (defined as a regimen containing at least three antiretrovirals) were considered for inclusion. Patients who had a viral load > 1000 copies/mL prior to attaining viral load <50 copies/mL were excluded.

Participants who experienced a viral load <50 copies/mL while on HAART were followed until they had a viral rebound, defined as 2 consecutive viral load results of > 500 copies/mL. Pre-HAART antiretroviral-naive patients were analyzed separately from those with nucleoside reverse transcriptase inhibitor (NRTI) experience.

Results

Of 3,565 suppressed antiretroviral-naive patients, 381 experienced viral rebound (rate, 6.26 events/100 person-years of follow-up [pyrs]);

Of 810 NRTI-exposed patients, 145 experienced viral rebound (rate of 8.29 events/100 pyrs);

In those with viral loads <50 copies/mL, certain drugs may be associated with higher rebound rates than others, the study authors conclude.

“Our study [findings] suggest that there appears to be an increased rate of viral rebound in regimens containing indinavir (Crixivan) or indinavir/ritonavir in previously antiretroviral-naive patients, with the rate of rebound being approximately twice that seen with efavirenz/EFV (Sustiva).”  In NRTI-experienced patients, the reverse was true.

The rate of viral rebound in previously antiretroviral-naive individuals was significantly higher in those receiving ddI/d4T (Videx/Zerit) and in those receiving other NRTI combinations.

“In treatment-naive patients, regimens containing soft gel saquinavir (Fortovase) and saquinavir/ritonavir and lopinavir/ritonavir (Kaletra) appeared to be associated with rates of viral rebound that are similar to those observed among patients receiving EFV,” write the authors.” They continue, “Our results also indicate that those receiving abacavir (Ziagen) are at a greater risk of virological failure, compared with those receiving efavirenz.” 

Patients in both the previously antiretroviral-naive group and the NRTI-experienced patients receiving nelfinavir (Viracept) were at an increased risk of virological failure, compared with those receiving EFV. The investigators also noted a trend toward higher rates of virological rebound in previously NRTI-experienced individuals receiving saquinavir-hard gel capsule (Invirase).

Finally, among the 2 main NNRTIs, “EFV is associated with a lower rate of virological rebound than nevirapine/NVP (Viramune).”

In the NRTI-exposed group, “no NRTI combination was associated with an increased rate of virological rebound among NRTI-experienced patients,” write the authors.

Other factors associated with increased risk for viral rebound were ethnicity (blacks were at increased risk) and the “nonheterosexual risk and non-homosexual risk group, which includes injection drug users, blood product recipients, other, and unknown.”

In recognition of the fact that it is important to make comparisons using observational data with caution, the authors closed by noting that their study was a retrospective analysis.

Table 1
Person-years of follow-up (pyrs) and number of virological rebounds according to exposure to nucleoside reverse transcriptase inhibitor (NRTIs).

Department of Primary Care and Population Sciences and Mortimer Market Centre, Royal Free and University College Medical School, Chelsea and Westminster Hospital, Medical Research Council Clinical Trials Unit, King's College Hospital, St. Mary's NHS Trust, and Royal Free Hospital, London, and Brighton and Sussex University Hospital, Brighton, United Kingdom.

09/19/05

References
1. C J Smith and others (for the United Kingdom Collaborative HIV Cohort Study Group). The Rate of Viral Rebound after Attainment of an HIV Load <50 Copies/mL According to Specific Antiretroviral Drugs in Use: Results from a Multicenter Cohort Study. Journal of Infectious Diseases 192. October 15, 2005. Epub September 14, 2005.

Link to FDA-approved Anti-HIV Drugs

PI NRTI nNRTI EI Aptivus Agenerase Crixivan Fortovase Invirase Kaletra Lexiva Norvir Reyataz Combivir Emtriva Epivir Epzicom Hivid Retrovir Trizivir Truvada VIDEX VIDEX EC   Viread Zerit Zerit XR Ziagen Rescriptor Sustiva Viramune Fuzeon Protease Inhibitors Non Nucleoside Reverse Transcriptase Inhibitors Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Entry / Fusion Inhibitors Link to Experimental Medicines in Development for AIDS