Recent infection and ART treatment interruptions are key periods for HIV transmission

A large proportion of HIV transmissions occur during recent infection or antiretroviral treatment interruptions, Swiss investigators report in Clinical Infectious Diseases. Overall, 44% of transmissions were associated with recent infection and 14% could be attributed to treatment interruptions. The authors believe these findings represent a major challenge for treatment as prevention (TasP) strategies.

“Our findings imply that TasP needs to be accompanied by interventions to tackle treatment continuity, adherence, retention in care, and, importantly, early diagnosis,” comment the investigators.

Previous studies have shown that between 10% and 80% of HIV transmissions are attributable to patients who were recently infected with the virus. Knowing the proportion of early phase transmissions is important, especially given the recent emphasis on the use of HIV treatment as prevention.

Indeed, the impact of treatment as prevention on the ongoing epidemic could be limited if a high proportion of transmissions originate in individuals with recent infection. A high proportion of such patients are unaware of their status and are therefore unable to benefit from HIV therapy. Moreover, because recent infection is associated with a very high viral load, individuals with this phase of infection are often highly infectious.

Investigators from the Swiss HIV Cohort Study therefore conducted a retrospective analysed of the genetic characteristics of stored blood samples obtained from Swiss HIV patients. Using a technique called phylogenetic analysis, they looked for infections with similar genetic profiles which were likely to be part of a transmission cluster.

A total of 19,604 genetic sequences from approximately 11,000 patients (59% of cohort participants) were available for analysis.

The year of HIV diagnosis for patients included in the analysis ranged from 1984 to 2014. Most (71%) were men, 77% were white and 38% were in the men who have sex with men (MSM) risk group.

Date of HIV seroconversion could be estimated for 4079 patients, and 82% of these individuals were diagnosed in the first year after seroconversion.

The investigators identified between 71 and 378 transmission pairs. Approximately two-thirds (62%-66%) involved MSM.

When recent infection was defined as the first year after infection, the median percentage of transmissions attribution to recent infection ranged from a low of 41% to a high of 44%. Using six months since seroconversion as the criterion for recent infection showed that between 28%-42% of transmissions had their source in patients with recent infection.

The authors then looked at transmissions during the chronic phase of HIV infection.

Higher viral load (p < 0.001), lower CD4 count (p = 0.04),  and longer time to initiation of antiretroviral treatment (p = 0.005) were all associated with transmissions.

Some 54 of the 121 people who transmitted HIV in the chronic-phase (45%) were known to have started HIV therapy. Viral load data were available for 44 of these individuals, and 35 had at least one measurement above 400 copies/ml (median detectable viral load, 70,800 copies/ml). The authors suggest the other nine patients could represent non-direct transmission pairs (for example, an intermediate transmitter), a false-positive cluster, or a missed detectable viral load measurement.

Additional data were obtained for the 35 people with a confirmed viral-load who transmitted in the chronic phase. For 18, the estimated data of transmission was very close to the date HIV therapy was initiated. “These individuals transmitted either briefly before or briefly after ART initiation”, suggest the authors.

All but one of the other 17 patients had a documented antiretroviral treatment interruption.

“Overall, these results indicate that a substantial fraction of chronic-phase transmission events – at least 17 of 121 (14%) and up to 54 of 121 (45%) – occurred after ART initiation by the transmitter,” comment the investigators. “This observation underlines the important contribution of treatment interruptions and the periods close to ART initiation for onward HIV transmission.”

They conclude, “our work highlights the high fraction of recent-phase transmission and transmission during therapy interruptions, two key challenges for curbing HIV incidence with TasP.”

Marzel A et al. HIV-1 transmission during recent infection and during treatment interruptions as major drivers of new infections in the Swiss HIV Cohort Study. Clin Infect Dis, online edition. DOI: 10.1093/cid/civ/732.