HIV treatment works well across all subtypes

HIV treatment works well, regardless of the subtype of HIV an individual is infected with, researchers from the UK report in the May 1^st edition of Clinical Infectious Diseases. They found little difference in the proportion of patients achieving and maintaining an undetectable viral load when analysed according to their subtype. Immune restoration, measured by the rate of CD4 cell gain, was also similar across the subtypes studied.

The dominant HIV subtype in Western Europe and the United States is subtype B. Therefore most clinical trials and observational studies have been performed in populations where subtype B predominates. This is despite the fact that this subtype represents only 12% of global HIV infections, with subtype C contributing approximately 48%.

In the UK and some other Western European countries, migration – particularly from Eastern and Southern Africa – means that physicians are now treating patients with a wider diversity of HIV subtypes. There is laboratory data that non-B subtypes may be less susceptible to some antiretroviral drugs, but the clinical significance of these findings is unknown. Furthermore, earlier research analysing the outcome of HIV treatment according to subtype has been limited by a number of factors.

Investigators from the UK Collaborative HIV Cohort Study and the UK Collaborative Group on HIV Drug Resistance therefore designed an observational study to analyse the effect of HIV subtype on virological and immunological responses to HIV treatment.

Their research involved 2116 patients who started HIV treatment for the first time between 1996 and 2006. These patients were infected with a variety of HIV subtypes including subtype B (73%), subtype C (13%), subtype A (3%), subtype CRF_AE (3%) and subtype D (2%). The remaining 6% of patients were infected with rarer subtypes including G, F, I, J and unclassifiable types.

There was a strong association between HIV subtype and ethnicity and risk group. Most (86%) cases of subtype B infection were in white patients, and 90% were in gay men. Conversely, 76% of subtype C infections were in black Africans and 87% of infections with this subtype were in heterosexuals.

Individuals were followed for a median of 39 months. An undetectable viral load was achieved by 97% of patients. After twelve months of triple-drug HIV treatment, 89% of patients with subtype B had an undetectable viral load compared to 94% of those with subtype C infection and 97% of those infected with subtype A. Furthermore, individuals with subtype C or A achieved an undetectable viral load more rapidly than those with subtype B (p = 0.02).

The investigators then restricted their analysis to the patients who achieved an undetectable viral load within six months to see if subtype affected the risk of viral load subsequently rebounding to detectable levels.

They found that rebound occurred in 18% of patients, and their first set of statistical analysis showed that the risk of this happening was 39% higher in those infected with subtype C than subtype B. However, this difference disappeared in subsequent analysis that controlled for potential confounding factors.

Nevertheless, the investigators still found that viral rebound was slightly more likely to occur in patients with subtype C than subtype B (adjusted hazard ratio, 1.40, 95% confidence interval 1.00 to 1.95, p = 0.05).

Next the investigators excluded patients whose increase in viral load was due to non-adherence or a treatment interruption. Taking these factors into account, they found no difference in the time to viral load rebound between subtypes.

Analysis was then undertaken to determine the effect of ethnicity and HIV risk group on the virological outcome of treatment. This showed that the interval between starting HIV treatment and achieving an undetectable viral load was shorter in patients of black African origin than white patients (p = 0.03) and amongst heterosexual women than gay men (p = 0.04).

Finally, the investigators looked at the impact of subtype on the recovery of the immune system. Patients infected with non-B subtypes had lower baseline CD4 cell counts than patients with subtype B infection and this difference persisted during HIV treatment. However, the rate at which CD4 cell count increased did not differ by subtype.

“Virologic and immunologic responses were excellent overall during a median follow-up period of 39 months, indicating that current regimens are equally effective regardless of the infecting subtype,” conclude the investigators.

An accompanying editorial states, “Modern antiretroviral therapy works well in the handful of non-B subtypes studied so far and will certainly save lives, independent of the subtype of the infecting virus.” However, the investigators believe that more research is needed to evaluate the effectiveness of antiretroviral therapy against the full spectrum of subtype.