Targeting Prevention of HIV-1 Transmission

Live from the Conference on Retroviruses and Opportunistic Infections (CROI) 2014

Presentation 1: Transmission Clusters, Recent Infection and STIs Among New HIV Cases: Implications for Prevention.

Two epidemiological studies presented at CROI 2014 provided interim data that continue to emphasize the importance of identifying and targeting high-risk groups for the prevention of HIV transmission. These groups include:

o People with newly diagnosed sexually transmitted infections (STIs)

o Younger men who have sex with men (MSM)

o Being linked to an HIV transmission cluster

o Engaging in condomless sex with a known HIV-positive partner on ART. 

The studies confirm past associations, and point to continued vigilance in the fight to prevent HIV transmission.

Hong-Ha M. Truong of the University of California San Francisco presented interim results from a study intended to look at the associations between STIs, newly diagnosed HIV-1 cases, and HIV-cluster linkages in San Francisco. The study used data from the San Francisco HIV/AIDS case registry, the San Francisco STD case registry, the San Francisco Department of Public Health Laboratory, and the UCSF Laboratory of Clinical Virology. Included in the study were San Francisco residents with newly diagnosed HIV infection between 2005 and 2011, linked to care at publically funded facilities, and with viral genotypes available for analysis. Multivariate logistic regression was used to assess associations.

Results included:

• 1311 new HIV cases met inclusion criteria. These were 86% male; 43% white, 27% Hispanic, 19% black, 7% Asian/Pacific Islander; 31% under age 30 at HIV diagnosis, and 77% MSM.
• 68% had no STI diagnosis before receiving an HIV diagnosis.
• Younger age was significantly associated with having a recent STI: 22% ages 24 and under had a recent STI diagnosis (OR = 4.5; P < .0001), as did 22% aged 25 to 29 (OR = 3.8; P = .0003). 
• One-quarter of patients with recently diagnosed HIV infection had also recently received a diagnosis of an STI. 
• More than half of recently diagnosed HIV cases were linked to an HIV transmission cluster.
• These associations remained significant in the multivariate model, including younger age.

“Recent HIV infection was associated with being diagnosed with an STI during the time interval that overlapped when HIV transmission most likely occurred,” Truong said. “The high rate of clustering that was observed among HIV infection cases indicates that recent STI infection may be associated with onward transmission of HIV.” 

Key points: These results can help pinpoint intervention opportunities-integrating HIV and STI testing services, screening for acute HIV infection among those with newly diagnosed STI, and utilizing STI partner services. They also point to the importance of preexposure prophylaxis (PrEP) for high-risk individuals, such as MSM in this population.

Presentation 2: HIV Transmission Risk Through Condomless Sex if HIV+ Partner on Suppressive ART: PARTNER Study.

The second study was presented by Alison Rodger from University College London, who described the interim results of the PARTNER study. This observational multicenter study is being conducted in 75 European countries and is looking at HIV serodifferent couples in which the positive partner is receiving ART. Specifically, the investigators looked at the risk of sexual transmission of HIV through condomless sex between partners.

Participants were advised about the need for consistent condom use, and the risk of transmission when having sex with a partner known to be HIV-positive. Every 6 months, both partners completed confidential risk behavior questionnaires. Viral loads were performed for HIV-positive partners, while the HIV-negative partners received HIV tests. Couples were eligible if they were having condomless sex, not using postexposure prophylaxis (PEP) or PrEP, and had a viral load <200 copies/mL within the past 12 months. HIV-1 sequencing and linkage analysis were performed if transmission occurred.

Results included:

• 767 couples (282 MSM couples, and 445 heterosexual) were eligible, with a similar median age for all groups, about 40 years.
• HIV-positive partners were well established on ART (median ranging from 5 to 10 years), with self-reported ART adherence ranging from 94% to 97%.
• There was a large number of condomless sex acts: MSM 16,400; heterosexual men 14,000; heterosexual women 14,000.
• Among HIV partners, 73% of women reported condomless vaginal sex with ejaculation;, and 40% of MSM reported condomless anal sex with ejaculation.
• No linked transmissions were found overall during follow-up.
• Extrapolation of the upper bound of the confidence interval translated into an overall 10-year HIV transmission risk of 4%, with 10% transmission risk for all type of anal sex, and 32% for receptive anal sex with ejaculation.

In the absence of ART, approximately 86 transmissions would have been expected.  The observed absence of transmission may have been related to ART. 

Given that these are interim results and the study is not yet completed, the short follow-up to date may also have been a factor. Longer-term follow-up would be expected to clear up this issue, as the statistical adjustments demonstrated in calculating the 10-year HIV transmission risk.

What the studies suggest

Although results for both studies are preliminary, taken together they point to several areas that could be targeted to decrease the risk of HIV transmission. They provide confirmation that targeting these higher-risk populations and/or behaviors in your care and patient education efforts continues to be important in preventing infection in your higher-risk patients.

Take-Home Points:

• Integrate HIV and STI testing services: screen for acute HIV infection among patients with newly diagnosed STI, especially among younger MSM. 
• Preexposure prophylaxis is particularly important among high-risk individuals.
• STI partner services is an important ally.
• There is probable continued need for condom use even among established serodifferent partners in which the positive partner is on ART, especially for high-risk behaviors such as anal sex with ejaculation.

References:

Moderators Rochelle P. Walensky, Harvard Medical School, Massachusetts General Hospital, and Ian M. McGowan, University of Pittsburgh, Pittsburgh. (Session O-3 Oral Abstracts March 4 2014: Prevention and Epidemiology: Evolving Trends

Presentation 1: Presented by Hong-Ha M. Truong, University of California San Francisco, Gladstone Institute of Virology and Immunology, with Sharon Pipkin, Department of Public Health, San Francisco, Kara O’Keefe, Department of Public Health, San Francisco, Brian Louie, Department of Public Health, San Francisco, Teri Liegler, University of California San Francisco, Willi McFarland, University of California San Francisco, Department of Public Health, San Francisco, Robert M. Grant, University of California San Francisco, Gladstone Institute of Virology and Immunology, Mark Pandori, Department of Public Health, San Francisco, Kyle Bernstein, Department of Public Health, San Francisco, and Susan Scheer Department of Public Health, San Francisco

Presentation 2: Presented by Alison Rodger, Research Department of Infection & Population Health, University College London, with Tina Bruun, Copenhagen HIV Programme, University of Copenhagen, Valentina Cambiano, Research Department of Infection & Population Health, University College London, Pietro Vernazza, Infectious Diseases, Cantonal Hospital, St. Gallen Switzerland, Vicente Estrada, Dept of Infectious Diseases, Hospital Clinico San Carlos, Madrid Spain, Jan Van Lunzen, Dept of Infectious Diseases, University Medical Center, Hamburg Germany, Simon Collins, HIV i-Base, London UK, Anna Maria Geretti, Institute of Infection & Global Health, University of Liverpool, Andrew Phillips, Research Dept. of Infection & Population Health, University College London, Jens Lundgren, Centre for Viral Diseases and the Copenhagen HIV Programme, University of Copenhagen and the PARTNER Study Group