This Week in HIV Research: It's Not Too Late to Quit
This week, we add to the vast mountain of evidence tying lung cancer risk to smoking -- but with an HIV-specific twist, and a caldera of hope for those who quit. We also learn about the antiretroviral properties of an anti-cancer drug; read how kidney markers are like canaries; and bemoan the dearth of robust knowledge on second-line HIV treatment options.
To beat HIV, you have to follow the science!
People Living With HIV More Likely to Die of Lung Cancer Than of AIDS
Lung cancer is as much as 13 times more likely than AIDS-related diseases to kill a person living with HIV (PLWH) if that person faithfully takes antiretrovirals but also smokes, an analysis published in JAMA Internal Medicine found.
HIV increases a smoker's risk for developing lung cancer, yet more than 40% of PLWH in the U.S. smoke compared to 15% in the general population. Researchers created a simulation to account for history and intensity of tobacco use; adherence to HIV medications; other smoking-related health risks; and other factors. They estimated that among 40-year-old PLWH, between 16% and 29% will die of lung cancer by age 80. However, if PLWH stop smoking at that 40-year mark, that percentage drops to between 4% and 8%, while among PLWH who never smoked, only slightly more than 1% will die of lung cancer.
Recognizing this cancer risk may motivate PLWH to quit smoking, study authors suggested. They recommended that helping PLWH to stop using tobacco be incorporated into standard care.
Investigative Cancer Drug Coaxes HIV Out of Hiding
The short form of a Bromodomain and Extra-Terminal motif (BET) protein, BRD4, represses HIV transcription while the virus is hiding, a study published in Molecular Cell found. When that version of the protein is stopped with a BET inhibitor drug, latent HIV is transcribed again. However, if only the long form of the protein is eliminated, the virus is not reactivated.
One BET inhibitor currently under investigation for cancer treatment is JQ1, according to a related press release issued by Gladstone Institutes. JQ1 and similar drugs could be used to either suppress the virus long-term or to bring it out of hiding so it can be targeted by antiretroviral medication. "Silencing and reactivating HIV are often seen as competing approaches, but I think they could actually be combined to develop more effective therapies in the future," researcher Melanie Ott, M.D., Ph.D., noted in the release, explaining that combining the approaches could kill some of the virus while repressing the remainder until a person's strengthened immune system can eliminate it.
Kidney Markers Could Be Early Warning Sign for Other Diseases
Middle-aged people living with HIV who are on antiretroviral therapy are more likely than the general population to develop kidney problems over time, an analysis published in The Journal of Infectious Diseases showed.
Researchers followed more than 850 Dutch 45-year-olds for about four years. Over half were PLWH. The primary analysis included only PLWH whose antiretroviral regimen did not change during the study period. Most in that group were taking tenofovir disproxil fumarate (TDF), which is known to have renal side effects. However, an additional model that included those who had switched medications (possibly to avoid TDF) still found renal function decline in the PLWH compared to the non-PLWH arm. Researchers hypothesized that the persistent inflammation caused by HIV may play a role.
An accompanying editorial suggested that testing for albuminuria, a sign for potential kidney disease, "may serve as the proverbial canary in the coal mine" for a variety of other diseases.
More Evidence on Second-Line HIV Treatment Alternatives Needed
Researchers called for more clinical trials to investigate alternative second-line antiretroviral treatments because their meta-analysis published in The Lancet HIV showed scant evidence to evaluate such regimens.
In 2016, the World Health Organization (WHO) recommended ritonavir (Norvir)-boosted atazanavir (Reyataz) or lopinavir (Kaletra) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) for those whose initial regimen fails to suppress their HIV. Clinical trial results published since then support the use of lopinavir, but there is too little evidence for atazanavir, study authors concluded. Because mutations in the virus of people who need second-line therapy may make NRTIs less effective, other regimens might be preferable.
One alternative, ritonavir-boosted lopinavir with the integrase inhibitor raltegravir (Isentress), was no worse than the WHO-recommended treatment. However, pricing and dosing considerations may limit its usefulness for resource-limited areas that rely on the WHO guidelines, study authors noted. "More clinical trials, particularly with alternative backbones and ritonavir-boosted darunavir, are needed to better guide WHO treatment strategy and policy, and to guide countries in their use of second-line regimens," they concluded.