This Week in HIV Research: When STIs Flock Together

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As much of the U.S. broils in a widespread summer heat spell, the HIV research cauldron boils on -- although its fire is fueled not so much by ambient temperature as by the passions of researchers. In our slate of recently published HIV-related studies this week, we learn that:

  • A pair of sexually transmitted infections (STIs), chlamydia and human papillomavirus (HPV), may work synergistically to enhance anal neoplasia risk in people with HIV.
  • Predictive modeling may help us identify people who can benefit most from pre-exposure prophylaxis (PrEP).
  • Long-term data affirm the liver benefits of curing hepatitis C (HCV) among people with HIV.
  • There may be signs of promise for two-drug integrase-based initial therapy.

Wipe your brow, clear the sweat out of your eyes, and let's dip ourselves in the cool, soothing waters of medical data. To beat HIV, you have to follow the science!


Anal squamous cell carcinoma associated with HPV infection

Chlamydia May Enhance Human Papillomavirus' Potential for Causing Anal Neoplasia

Among men who have sex with men (MSM) and are living with HIV, Chlamydia trachomatis infection may enhance the potential of HPV to cause high-grade anal intraepithelial neoplasia, researchers reported in Clinical Infectious Diseases.

HPV DNA was found in 88% of 145 participants, and chlamydia in 9%; 24% had neoplasia. Univariate models showed a significant interaction between HPV genotype 16 -- the most prevalent genotype, at 26% of participants -- and chlamydia, but HPV genotypes 53 and 70 were also associated with neoplasia. Additional data are needed to confirm these findings, but genotypes 53 and 70 may need to be included in HPV screening panels, study authors noted.

Participants with either HPV16 or chlamydia were less likely to have neoplasia than those with both infections, suggesting that chlamydia increases the potential for HPV16 to cause anal neoplasia, and subsequently anal cancer, authors said. They recommended that MSM living with HIV be screened for chlamydia, which often causes no symptoms.


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Machine Learning May Help Identify High-Priority PrEP Candidates

An HIV prediction model based on electronic health records in California correctly identified as "high" or "very high" risk 46% of the 83 men in the cohort who had seroconverted -- but failed to correctly spot all 14 of the women, a study published in The Lancet reports.

The purpose of the algorithm was to flag people at high risk of acquiring HIV and thereby identify those who might benefit from PrEP. Using a large health system's dataset, the researchers developed HIV risk scores based on one group of patients in the system and applied these scores to another set of patients in the same database.

Much of a woman's risk for acquiring HIV depends on her partner's risk, which may explain the model's lack of identifying the women, study authors noted. A similar machine learning algorithm using data from Massachusetts identified 38% and 46% of seroconversions, respectively, within the Atrius Health system and the Fenway Health system, both of which have high rates of HIV diagnoses. That tool also flagged people who might be good candidates for PrEP.

"Identifying individuals who may benefit from PrEP is a major challenge for clinicians, and this is an important advance that could help improve PrEP delivery and use," commented Dianne Rausch, Ph.D., of the National Institute of Mental Health, in a press release.


Liver tissue under microscope
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Hepatitis C Cure Dramatically Curbs End-Stage Liver Disease Among People With Coinfection

Among people living with HIV, rates of cardiovascular disease and non-AIDS-defining malignancies were similar across hepatitis C statuses, but rates of end-stage liver disease were not, a large pan-European study published in Clinical Infectious Diseases showed. The study affirms the long-term clinical benefits of effective HCV therapy for the livers of people with HIV/HCV coinfection.

In the study, 16,618 participants living with HIV were stratified into five groups: no HCV, resolved HCV on their own, chronic untreated HCV, cured HCV, or experienced HCV treatment failure. Median follow-up was more than eight years. Compared to those cured of HCV, participants who were HCV antibody negative or who spontaneously cleared that virus were less likely to develop end-stage liver disease, whereas those with untreated chronic HCV or whose HCV treatment was unsuccessful were significantly more likely to do so.

Aside from the liver findings, this analysis found that, contrary to studies that only examined people with hepatitis C monoinfection, people with coinfection did not experience fewer heart problems or malignancies after they had been cured of HCV. A related commentary speculated that the relatively young cohort age (median 41 years), as well as controlling for smoking and diabetes, may explain the different outcome. Commentary authors called for even longer-term research into the effect of HCV cure on other outcomes, as well as its impact on stigma. Data on mental health, harm reduction, and other non-medical issues are also needed, they added.


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Network Meta-Analysis Suggests Promise for Two-Drug First-Line Regimen

In treatment-naive people, the two-drug combination dolutegravir/lamivudine (Dovato) shows similar outcomes to three-drug antiretroviral regimens, a study funded and partly designed by the drug's manufacturer, ViiV Healthcare, and its parent company, GlaxoSmithKline, showed. The network meta-analysis of 14 HIV drug regimens was published in AIDS.

At 48 weeks, virologic suppression rates were "broadly similar" between the study regimen and the three-drug combinations analyzed, with proportional differences ranging from -2.7% for dolutegravir/tenofovir alafenamide/emtricitabine to 7.3% for efavirenz/tenofovir disoproxil fumarate/emtricitabine.

Arguing in favor of two-drug therapy, the study authors noted that the longer lifespan of people living with HIV means more exposure to cumulative drug toxicities from antiretroviral treatment, and they suggested that two-drug regimens reduce that exposure. They also argued that randomized controlled trials to directly compare antiretroviral regimens are costly, making network analyses an appropriate substitute for such trials.

That said, study authors conceded that large differences in the distribution of effect modifiers may invalidate the results of such an analysis, and they allowed that different definitions of "networks" may produce different results. Nonetheless, the results of this particular network analysis support the use of dolutegravir/lamivudine instead of three-drug regimens, they concluded.