People who aren't taking HIV treatment are a major source of transmitted resistance in Swiss gay men

Individuals who have never taken antiretroviral therapy (ART) are the main source of transmitted HIV drug resistance among gay men, Swiss research published in the online edition of Clinical Infectious Diseases shows. The investigators matched people enrolled in the Swiss HIV Cohort Study with a linked drug resistance database. It was possible to identify a potential source for most of the participants with transmitted dug resistance. Up to 86% of these people may have been infected by a treatment-naive individual.

“Early treatment of patients with drug-resistant HIV would reduce the circulation of resistant viruses in the ART-naïve population and interrupt this vicious cycle,” comment the authors.

It is possible for HIV to become resistant to antiretroviral drugs, and drug-resistant virus can be transmitted between individuals. The presence of transmitted drug resistance can limit treatment choices before someone has taken a single anti-HIV drug.

Usually the source of transmitted drug resistance remains unknown. However, it is possible to see if infections are linked or clustered using a technique called phylogenetic analysis. Participants in the Swiss HIV Cohort Study were therefore linked with samples in a national drug resistance database to see if clusters of HIV infections involving transmitted drug resistance could be identified and if the potential source patients were taking HIV therapy or were antiretroviral naive.

The study sample comprised 1674 gay and other men who have sex with men (MSM) who were newly infected with HIV-1 subtype B infection between 1996 and 2009. Samples from all 6934 people with samples in the national drug-resistance database were used to construct the phylogenetic tree.

Approximately two-thirds (67%) of the study population belonged to a transmission cluster consisting of one of more linked infections.

There was an 8% prevalence of transmitted drug resistance among the 1674 participants. People with transmitted drug resistance were more likely to be diagnosed during primary infection than those with wild-type virus (OR = 1.51; 95% CI, 1.06-2.14, p = 0.02).

Most people (81%) were infected with virus that was resistance to a single class of antiretrovirals, but 11% had resistance to drugs in two classes and 7% were resistant to drugs in all three main classes of anti-HIV drugs.

Well over half (58%) the participants with transmitted resistance were associated with a transmission cluster where it was possible to identify at least one potential source individual.

Of the participants with transmitted resistance and an identified potential source, 86% (43 of 50) had at least one antiretroviral-naive patient as a potential source. In contrast, only 34% of patients with transmitted resistance belonged to clusters where there was a potential source patient who was taking HIV treatment.

“Most resistance mutations were transmitted to > 1 naive individual, and a single initial event from a treated patient may lead to several new infections with drug-resistant HIV,” write the authors.

The potential source for 51.5% of infections involving transmitted resistance involved people with primary HIV infection; this contrasted with 30.5% of people who did not transmit resistant virus.

Two long transmission chains were identified. Both involved transmission of virus with the L90M mutation which confers resistance to some older protease inhibitors. The first cluster comprised two treated patients and seven treatment-naive individuals; all eleven people in the second cluster were antiretroviral naive.

The L90M mutation confers resistance to nelfinavir and saquinavir. These antiretrovirals were taken by 30 and 10%, respectively, of patients in the Swiss Cohort in the late 1990s, but by the mid 2000s fewer than 5% of patients were treated with these drugs. However, this was not accompanied by a similar decrease in the incidence of transmitted virus with the L90M mutation. “This strongly suggests continuing transmission among naive patients, independent of ART usage,” write the investigators, “as does our finding of large 90M transmission chains dominated by ART-naive transmitters.”

The authors believe their findings “indicate a high potential for HIV drug resistance to circulate among treatment-naive patients. This highlights the importance of limiting the acquisition of drug resistance before it becomes established in untreated patients, and of early test-and-treat strategies to prevent resistance transmission from untreated patients.”