This Week in HIV Research: Delivering Care Through Uncertainty

A study and concurrently published commentary in a recent issue of The Lancet HIV encapsulate the ongoing uncertainty regarding the role HIV status plays in COVID-19 severity and outcomes.

In the retrospective study, primary care records for more than 17 million people in the UK (0.16% of them indicating positive HIV serostatus) were cross-referenced with death certificates, yielding 14,882 COVID-19 deaths, 25 of which were among PLWH. PLWH were younger, and more likely to identify as Black and male, than HIV-negative participants.

Although the absolute number of PLWH who died from COVID-19 causes was low, the relative proportion was higher among PLWH than HIV-negative people, the study found—a finding that suggested a need to prioritize PLWH for COVID-19 vaccination, the authors argued.

However, a pair of leading experts countered in an accompanying commentary that the overall scarcity of data and the high comorbidity rate among PLWH undermine the reliability of the study results. The commentary was authored by Laura J. Waters, M.D., FRCP, who is the chair of the British HIV Association, and Anton L. Pozniak, M.D., FRCP, who is a former president of the International AIDS Society.

Waters and Pozniak noted that Black people are more likely to work in occupations that put them at higher risk of acquiring SARS-CoV-2, and that PLWH without key comorbidities may also not report their serostatus to their primary care provider, potentially biasing the HIV-positive dataset. Absent those comorbidities (which were present for 23 of the 25 PLWH who died), the risk of death did not differ by serostatus, they stated.

Waters and Pozniak wrote that they considered the study findings important, but cautioned that more specific, controlled data are needed before drawing conclusions.

A British study published in AIDS found a clear association between smoking tobacco and the risk of developing cancer in PLWH, but no attenuation of this link based on viral suppression level or CD4 count.

Researchers analyzed data from 19,602 participants in the RESPOND cohort, 3% of whom were classified in a “poor” CD4 count/viral load stratum (i.e., CD4 count below 350 and viral load above 200), 52% in a “good” stratum (i.e., CD4 count above 500 and viral load below 200), and 45% in an intermediate stratum between the other two. At baseline, 41% reported never having smoked, 44% smoked at the time, and 14% had previously smoked.

There were 513 incident cancers, for an overall rate of 6.9/1000 person-years of follow-up. No relationship was seen between a person’s smoking history, CD4/viral load stratum, and cancer incidence. However, cancer rates were higher among current smokers compared to those who never smoked, and were higher among participants in the poor CD4/VL stratum compared to those in the good stratum.

Several limitations should be noted: lack of data on duration, intensity, or type of smoking; no information on family history, alcohol use, and other potential cofounders; and mostly white participants.

Although the findings imply that smoking does not enhance HIV viral replication, further studies on that interaction are needed, study authors wrote. Regardless, “Reducing the burden of cancer from smoking and uncontrolled HIV infection should remain a priority for all HIV-positive individuals,” they concluded.

Starting antiretroviral therapy on integrase inhibitor (INSTI)-based regimens, relative to starting on non-INSTI regimens, increases the likelihood of CD4/CD8 count normalization and optimal immunological recovery—but coinfection with cytomegalovirus (CMV) reduces that likelihood, an Italian study published in Journal of Acquired Immune Deficiency Syndromes showed.

Current U.S. HIV treatment guidelines preferentially recommend INSTIs as first-line treatment due to their efficacy and tolerability. This study confirms that choice, adding immunology as a further factor in favor of INSTI use.

The 1,428 treatment-naive participants in the retrospective multicenter study were not randomized: 22% started on INSTI-based regimens, 45% on PI-based regimens, and 34% on NNRTI-based regimens. The study assessed markers—CD4/CD8 ratio and an index called OIR, which is composed of CD4 count, CD4 percentage, and CD4/CD8 ratio—that can indicate unbalanced immune function despite virological control and CD4 count increase.

After a median 13 months of follow-up, the overall CD4/CD8 count had normalized in 39% of participants, and OIR was normalized in 33%. The probability of both markers normalizing was higher for those on INSTI-based treatment, with the exception of one key subset of participants: the 55% of participants who had positive CMV antibodies at baseline.

Better tolerability for INSTIs may have increased adherence, the study authors theorized; conversely, they suggested, CMV’s association with socioeconomic disparities may have resulted in lower adherence among that group, thus suppressing lab normalization. (Neither socioeconomic factors nor adherence were recorded in the study.)

The study authors called for CMV testing to identify those at risk of immunological failure, along with further clinical trials to learn whether the treatment of asymptomatic CMV might improve immune recovery.

A smart pill bottle service may increase treatment adherence in PLWH, a small single-site pilot study published in Journal of Acquired Immune Deficiency Syndromes found.

The medication containers report real-time data to a central service, which sends phone or text messages to people who have not opened their bottle at the correct time. The study enrolled 63 participants on tenofovir-containing regimens and measured TFV-DP levels, a marker of TDF adherence, in dried bloods spots. Thirty people, two of whom were lost to follow-up before the baseline visit, were randomized to the pill bottle arm and 33 to the control arm. Everyone received adherence counseling.

At the end of the 12-week study, TFV-DP levels were higher in the smart pill bottle group than in the control group, indicating about one additional tenofovir dose per week.

TFV-DP levels can be affected by drug-drug interactions, especially with modern hepatitis C medications, the use of tenofovir alafenamide instead of tenofovir disoproxil fumarate, and other factors, study authors acknowledged. They called for further exploration of smart pill bottles as adherence support devices for both HIV treatment and pre-exposure prophylaxis (PrEP).

One of the study’s authors is an employee of the smart pill bottle manufacturer, which also supplied the bottles and service for the study.