Rate of transmitted drug-resistant HIV stable in France

The rate of transmitted drug-resistant HIV remained stable in France in the ten-year period after the introduction of effective HIV treatment, investigators report in the March 27^th edition of AIDS. In 2006, 11% of patients with primary HIV infection had resistance to at least one antiretroviral drug, little different from the 8% observed in 1996 and a fall on the 12% seen between 2000 and 2004.

Stability in the frequency of transmitted resistance is attributed by the investigators to the efficacy of HIV treatment. They note that in 2006 the vast majority of patients taking HIV treatment had a viral load below 50 copies/ml.

The investigators also found that the prevalence of non-B subtypes of HIV increased during the study period, largely due to migration to France by individuals from French-speaking parts of Africa.

Estimates of the frequency of transmitted drug-resistant HIV in Europe and North America vary between 5 and 25%. Recent studies examining this issue have yielded conflicting results. Although some studies have found that rates of resistance have increased in patients newly infected with HIV, other studies have found the opposite.

In order to better understand this issue, investigators looked at rates of transmitted HIV drug resistant amongst individuals diagnosed with primary HIV infection between 1996 and 2006. The investigators focused on the period 2005 to 2006. The prominent subtype of HIV circulating in Europe is subtype B, and the investigators also conducted analyses to see if there had been an increase in the prevalence of non-B HIV subtypes in France during the study period.

Between 1996 and 2006, a total of 1446 individuals were diagnosed with primary HIV infection in France and these patients formed the study population.

Primary resistance in 2005-2006

In 2005 to 2006, 415 individuals were diagnosed with primary HIV infection. These individuals had a median CD4 cell count of 490 cells/mm³ and the median viral load was 200,000 copies/ml. Most (89%) were men, with 65% being gay or bisexual.

Resistance to at least one antiretroviral drug was present in 11% of patients. Only 2% had resistance to drugs from two or three classes of antiretrovirals. Resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) was present in 6%, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 5%, and 2% had resistance to a protease inhibitor.

Next the investigators looked at the prevalence of resistance to individual antiretroviral drugs. The rate of resistance was highest (5%) to the older NRTIs, AZT (zidovudine) and d4T (stavudine, Zerit). There was a low prevalence (below 1%) of resistance to the newer NRTIs, tenofovir (Viread, also in the combination pills Truvada and Atripla) and abacavir (Ziagen, also in the combination pills Kivexa and Atripla).

Approximately 5% of patients had resistance to the NNRTIs efavirenz (Sustiva, also in the combination pill Atripla) and nevirapine (Viramune). There was a very low (below 1%) prevalence of resistance to the ritonavir-boosted protease inhibitors.

There were no significant differences in the viral load or CD4 cell counts of patients with and without primary resistance.

Next the investigators looked at trends in rates of transmitted resistance over time. No significant change in the proportion of patients with resistance to at least one drug was observed between 1996 and 98 (8%) and 2005 and 2006 (11%).

The only class of antiretroviral drugs where the rate of transmitted resistance increased was NNRTIs. In 1996 to 1998, fewer than 1% of patients in France had resistance to an NNRTI, but this increased to 4% by 1999 following the introduction of this class of drug into France.

Use of HIV treatment expanded significantly in France during the period of the study, but did not result in an increase in the rate of transmitted resistance. In 1996, only 28% of HIV-positive individuals were taking antiretroviral therapy, but this had increased to 81% by 2006. The proportion of patients with a viral load below 500 copies/ml increased from only 17% in 1996 to 85% in 2006. Furthermore in 2006, 75% of patients taking HIV treatment had a viral load below 50 copies/ml. The investigators suggest that improved virological control of HIV is the explanation for the stability in rates of transmitted resistance.

Finally the researchers looked at the prevalence of non-B subtypes of HIV in France. In 2005 to 2006, 26% of patients with primary infection had non-B HIV. By 1996 to 1998, 10% of patients with primary infection had non-B HIV, and this had increased to 24% by 2002. Migration to France from individuals from French-speaking parts of Africa was identified by the investigators as the cause

Approximately 50% of non-B HIV infections were diagnosed in heterosexuals in 2005 to 2006. But the investigators noticed that there was an increase in the prevalence of non-B subtypes amongst gay men (1998, 6% increasing to 16% in 2006, p = 0.02), suggesting transmission of non-B HIV in France.

The investigators conclude that their large epidemiological survey showed “a stable frequency of transmitted resistant virus over time.” They add, “we clearly confirm an increase in non-B strains in France”, and continue “our results strengthen the French guidelines which recommend performing genotypic resistance tests at the time of primary HIV infection or prior to treatment initiation.”