This Week in HIV Research: Resistance (Testing) Is Futile
Lovers of the 1980s television series Star Trek: The Next Generation probably remember a recurring and terrifying enemy: the Borg. (For the rest of you, please don't abandon this article; we promise it'll stay relevant. Mostly.) This alien species singularly focused on subsuming all life in the galaxy into their collective hive mind; whenever the Borg encountered a new target for assimilation, they would instruct it not to bother fighting by using a morale-crushing war cry: "Resistance is futile."
Naturally, Star Trek being Star Trek, the good guys won in the end. It turned out that resistance wasn't futile after all.
Resistance, of course, is a persistent enemy in HIV medicine as well -- and a primary focus of the recently published research we highlight this week. Among the questions this research poses is an intriguing one: HIV drug resistance may not be futile, but how about testing for certain types of it? This week's plotlines include:
- New findings suggest that, at least in high-income countries, there may be little need for drug resistance testing prior to antiretroviral therapy initiation.
- At the same time, evidence of high-level drug resistance remains robust among viremic people living with HIV in the U.S.
- Another thing that remains robust among people living with HIV (PLWH), despite the potency of modern antiretrovirals: pneumonia incidence.
- Remember the U.S. National HIV Strategy? When it comes to achieving prevention goals, its results have been deeply mixed thus far.
Let's boldly go where HIV researchers have recently gone before. To beat HIV, you have to follow the science!
Do We Still Need to Test for Transmitted HIV Drug Resistance?
Testing for transmitted drug resistance (TDR) before starting antiretroviral therapy for HIV may not be necessary in high-income countries, a large study found. The findings, which were published in the Journal of Acquired Immune Deficiency Syndromes, are based on data from Canada and Europe.
Sixty-seven percent of the study's 25,672 HIV treatment-naive participants were tested for drug resistance, but only 6% of those tested had intermediate- or high-level resistance to one or more antiretrovirals, and 5% of those with transmitted resistance started treatment with a drug to which they were resistant. Similar findings also held for the 44% of participants who presented late for HIV diagnosis.
Initial drug resistance testing had little effect on estimated 5-year viral suppression rates (77% for those tested compared to 74% for those not tested) and 5-year risk of AIDS or death (no difference between groups).
Factors supporting an argument for skipping TDR include the fact that testing results take about two weeks, delaying the start of treatment, and the fact that effective second-line options exist for the few people resistant to first-line treatment, study authors noted. On the other hand, the results of this study may not apply to low-resource settings or specific populations where HIV strains resistant to some antiretrovirals are common, the authors cautioned. They called for additional research into exactly who might benefit from selective testing for transmitted drug resistance.
High Rates of Drug Resistance Seen Among Viremic MSM
A small study in the U.S. found substantial drug resistance among men who have sex with men (MSM) living with HIV who had a viral load of 1,000 copies/µL or higher at baseline, researchers reported in AIDS.
Thirty-one percent of 142 participants had high-level resistance against one or more antiretrovirals, with 8% resistant to integrase strand transfer inhibitors and 12% resistant to more than one drug class. While phylogenetic analysis did not detect geographic clusters, drug resistance rates were significantly higher in Birmingham, Alabama (53%) than in Baltimore, Maryland (29%), Boston, Massachusetts (26%), or Atlanta, Georgia (21%).
An earlier study by the same authors found that > 50% of those resistant to an antiretroviral were resistant to at least one component of tenofovir disoproxil fumarate/emtricitabine (Truvada), which is used for pre-exposure prophylaxis (PrEP). "These findings highlight the need for improved HIV care in this high-risk population, identification of alternative regimens for PrEP, and inclusion of integrase resistance testing when selecting [antiretroviral] regimens for MSM in the United States," study authors concluded.
Pneumonia Risk Is Still Persistently Higher for People Living With HIV
Among PLWH, rates of invasive pneumococcal disease and community-acquired pneumonia remain considerably higher than among the general population, a Dutch study reported in Clinical Infectious Diseases showed.
The examination of pneumonia cases in Dutch PLWH focused on a period beginning in June 2008 and ending in December 2017, thus encompassing recent improvements in HIV treatment within a high-income country. Nonetheless, the study found that PLWH were diagnosed with invasive pneumococcal disease at a rate more than seven times higher than the Dutch population as a whole, and were diagnosed with community-acquired pneumonia at a rate more than eight times higher.
Lung infection rates were higher among PLWH with lower CD4 counts but continued to exceed general population rates even at CD4 cell counts > 500 cells/µL (PLWH: 946/100,000 patient years of follow up compared to 188/100,000 in the Dutch population). Such higher risk may be related to persistent humoral immune defects that limit the body’s protection against capsulated bacteria in PLWH, study authors theorized, as well as due to lifestyle factors, such as smoking.
Although vaccinating all PLWH against pneumococcal infection is recommended internationally, guidelines in the Netherlands suggest such vaccinations only if there are additional risk factors. The study authors recommended expanding pneumococcal vaccination in the Netherlands in line with international recommendations.
However, a commentary published alongside the Dutch study pushes against the suggestion that pneumococcal vaccination be expanded in the Netherlands. Elizabeth R. Jenny-Avital, M.D., of the Jacobi Medical Center in New York City discussed two common vaccines and their respective effectiveness in certain populations, concluding that “Many questions regarding the deployment [of] pneumococcal vaccine in people living with HIV and other high-risk patients remain, including optimal timing, frequency, adjuvant, and surrogates of protection.” Meanwhile, providers should address modifiable risks, such as smoking, and test everyone with a pneumococcal infection for HIV, she advised.
Success of National HIV Strategy "Decidedly Mixed"
A 2018 survey among a probability-based cohort of 502 gay and bisexual men in the U.S. paints "a decidedly mixed picture" of the success of the prevention component of the National HIV Strategy, the study's authors wrote in Journal of Acquired Immune Deficiency Syndromes.
While life-time testing (81%) and viral suppression (95% of those living with HIV) rates were high, so were rates of recent condomless anal sex (54%). "What is most concerning is that only 6.7% of HIV negative/unknown men were on PrEP -- and 54% of them had condomless sex in the past six months," commented study author Brian M. Dodge, Ph.D., in an email to TheBodyPro. A forthcoming paper will delve into the reasons for the low PrEP uptake, Dodge said, noting that many respondents outside large cities were unaware of this form of HIV prevention.
While 62% of respondents were willing to discuss sex with men with their primary care provider, only 36% reported having spoken about HIV prevention with their provider. Study authors suggested that health care providers be trained to address these questions with their patients in order to reach those who may not receive their care at an LGBT-identified center. They also advocated for wider dissemination of PrEP and condom use messaging. Finally, more comprehensive assessments of HIV prevention outcomes are needed to better evaluate the national strategy, they concluded.