Successful diagnosis of acute/early HIV infections may have contributed to fall in HIV incidence in San Diego

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An HIV testing programme targeting individuals with acute/early infection likely contributed to a decline in incident infections in San Diego after 2008, investigators report in Clinical Infectious Diseases.

The “Early Test” initiative was launched in 2007 and involved negative HIV antibody tests being rescreened using nucleic acid testing (NAT) – a technique capable of detecting HIV infections within 7-10 days after exposure. A fall in new HIV diagnoses was observed in proportion to the number of acute/early infections diagnosed. Moreover, molecular analysis showed that transmission networks were more likely to terminate in the zip codes where the testing campaign was marketed.

The testing initiative was targeted at men who have sex with men (MSM) living in specific zip codes in the central San Diego area.

Glossary

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

hypothesis

A tentative explanation for an observation, phenomenon, or scientific problem. The purpose of a research study is to test whether the hypothesis is true or not.

epidemiology

The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

primary infection

In HIV, usually defined as the first six months of infection.

“Our analyses demonstrated that the observed decrease in incident diagnoses was associated with the steady increase in testing by the Early Test program,” comment the authors.

Over 1 million individuals in the United States are infected with HIV and there are 50,000 new diagnoses each year. Between a third and a half of all new infections are thought to originate in individuals recently infected with HIV. Acute/early/primary HIV infection is characterised by a very high viral load, meaning that patients are potentially very infectious to their sexual partners. Moreover, most patients with this phase of HIV infection are usually unaware that they have been infected with the virus.

Diagnosing patients with acute/early HIV is therefore a public health priority. In 2007, the Early Test programme was introduced in San Diego. Its marketing targeted MSM living in the central area, especially zip codes 92103 and 92104.

Investigators designed a study to evaluate the impact of this testing programme on trends in local HIV incidence. To do this, they used epidemiological, geographic and molecular sequencing information.

Between 2006 and 2012, an average of 471 new HIV diagnoses were made each year in San Diego County. The distribution of the number of diagnoses between the six local health areas in the county remained stable during this period. The central region consistently had the highest HIV prevalence, and within the central region, the zip codes 92103 and 92104 had the highest prevalence rates (5.7% and 4%, respectively). These zip codes are at the centre of the San Diego gay community.  

The Early Test programme conducted 20,111 tests and made 460 diagnoses by the end of 2012.

Infections were defined as acute if the patient lacked antibodies but had a positive NAT result, and as early if they were antibody positive and had serologic and virologic characteristics consistent with infection for six months or less.

Each year between 2008 and 2012 the programme diagnosed an average of 17 acute (19.6% of all diagnoses) and 21 early (24.3% of all diagnoses) infections.

During this period, 171 people in the 92103 and 92104 zip codes were diagnosed by the programme and evaluated for recent infection; 54% of these infections were acute or early (22% acute).

Patients living in the 92103 and 92104 zip codes were more likely to be diagnosed with acute/early infection compared with residents elsewhere in San Diego (54% vs. 44%, p = 0.04).

The investigators used new diagnoses as a proxy for HIV incidence and assumed that the rate of new infections was driven by factors including, region, year, the number of tests performed by the Early Test programme and the number of infections it detected.

They found that the number of tests performed by the programme was positively associated with a significant reduction in HIV incidence (p < 0.001).

Other possible reasons for this fall in the rate of new infections were discounted by the authors. These included a reduction in sexual risk (rates of sexually transmitted infections increased in the study period), more effective HIV therapy (there was a significant increase in the number of ART-treated patients in San Diego who experienced virologic failure during the period of analysis), national incidence trends or the availability of pre-exposure prophylaxis (PrEP).

Molecular sequencing enabled the investigators to identify transmission networks involving patients diagnosed with acute/early infection. They calculated the net direction of HIV transmission, into or out of specific zip codes. Compared to all other zip codes, 92103 and 92104 had the highest net importation, whereas several other zip codes had the highest next exportation.

“This suggested,” write the investigators, “increased HIV transmission chain termination in the 92103 and 92104 zip codes, areas targeted by the Early Test program.”

Individuals living in zip codes 92103 and 92104 were more likely to be diagnosed with acute/early infection compared to residents of other areas (34.2% vs. 27.3%), suggesting that patients living in areas other than those targeted by the Early Test programme had a delay between infection and diagnosis. However, there was no difference in the time between diagnosis and initiation of HIV therapy between patients in the two central zip codes and patients living in other areas.

“These results support the hypothesis that the Early Test program targeted at MSM living in 92013 and 92014 zip codes led to increases in the diagnosis of AEH [acute and early HIV] infection and may help explain the observed decrease in incident HIV diagnoses in the Central region,” comment the authors.

They conclude, “early HIV diagnoses by the primary infection screening program probably contributed to the observed decrease in HIV incident diagnoses in San Diego since 2008 and suggest that testing programs, which can diagnose AEH infection, should be expanded among high-risk populations.”

References

Mehta SR et al. Using HIV sequence and epidemiologic data to assess the effect of self-referral testing for acute HIV infection on incident diagnoses in San Diego, California. Clin Infect Dis, online edition. DOI: 10.1093/cid.ciw161 (2016).