This Week in HIV Research: Early Screening Matters, and Not Just for HIV

Adult women living with HIV experience more non-AIDS comorbidities than HIV-negative women, with the most pronounced differences in comorbidity burden occurring at the youngest ages, a U.S. study published in Clinical Infectious Diseases found.

Data on 3,129 participants in the Women’s Interagency HIV Study, 890 of whom were HIV-negative, found that non-AIDS comorbidities began occurring in significant numbers among women in their 20s regardless of HIV status, with greater blood pressure increases noted in particular. However, high blood pressure and other risk factors arose earlier in the lives of WLWH than in HIV-negative women.

Overall, non-AIDS comorbidity incidence was 48% higher among WLWH under the age of 25 than their HIV-negative counterparts (after adjusting for demographic factors such as race, drug/alcohol use, body mass index, and income level). By comparison, incidence was 36% higher among WLWH age 55 or over, and ranged widely from 1% (among 40- to 44-year-olds) to 31% (among 25- to 29-year-olds) within a stratified set of five-year age groups between 25 and 55.

The study authors noted that prior research showed steep blood pressure increases occurring sooner in life among women than men. The cause of these observed differences in women with HIV is likely multifactorial, they contend, including ongoing inflammation, long-term antiretroviral therapy exposure, lower estrogen levels in menopausal women (which may occur earlier in WLWH than HIV-negative women), and social determinants of health.

The study also found that several other non-AIDS comorbidities occurred at higher rates, most notably (in order) chronic kidney disease, liver disease, cancer, psychiatric illness, dyslipidemia, and bone disease.

Age-based general population screening guidelines may be inadequate for PLWH, and especially for WLWH, study authors wrote. In addition to earlier screening, they called for sex-stratified guidelines and risk assessment tools that account for both HIV status and sex. “Our data highlight the need to prioritize WLWH, particularly young women, for early NACM screening to identify those at highest risk of amassing comorbidities and to offer timely, targeted risk-modification interventions,” they concluded.

PLWH experience type 2 myocardial infarctions more frequently than the general population, while the opposite is true for type 1 heart attacks, researchers reported in the Journal of Acquired Immune Deficiency Syndromes.

Type 1 MIs are caused by atherosclerotic plaque. Type 2 MIs are due to sepsis- or cocaine-induced vasospasms and are more deadly than Type 1 MIs. Incidence frequency changes as people age, with T2 less common in general and more likely in older people. Prevention and treatment approaches vary between the two types.

Among the 875 PLWH who experienced a heart attack and who were included in this study (462 T1MI, 413 T2MI), T2 rates were significantly higher than T1 in people < 40 years old, while T1Ms were more common than T2MIs in those > 50 years old.

Sepsis caused 36% of T2 events (compared to 19% in the general population) while cocaine/drug use was responsible for 11%. Intravenous drug use was an HIV risk factor in 21% of those with a T1MI and in 36% with a T2MI. Most participants with sepsis-induced heart attacks had very low nadir CD4 counts.

Study authors called for more research, concluding: “A better understanding of these important comorbidities, who is impacted, when, and why, is needed to further comprehend the underlying mechanisms and successfully intervene to improve long-term outcomes for older PLWH as the population in care continues aging.”

Among the three major sets of European guidelines regarding the identification and treatment of cardiovascular risk in PLWH, wide variations exist that can complicate the process of assessing risk and selecting interventions, researchers report in PLoS One.

The study retrospectively examined data from a cohort of 389 PLWH (80% men) who were patients at an HIV outpatient clinic in Lodz, Poland, between November 2018 and January 2020. Their CVD risk level and their ability to achieve therapeutic levels of low-density lipoprotein (LDL) were then assessed using three different assessment tools (D:A:D, Framingham, and SCORE) and three sets of guidelines (EACS, ECS/EAS, and PTN AIDS).

One illustration of the differences between the guidelines were the extent to which therapeutic LDL values were found to have been achieved among study patients: According to EACS guidelines, that rate was 17%; according to ESC/EAS guidelines, it was 12%; and according to PTN AIDS guidelines, it was 44%.

Additionally, most tools for assigning CVD risk levels either do not consider HIV status, or (as is the case with the D:A:D scale) assume patients are taking older antiretrovirals, the study authors noted.

The study authors noted that half of the study participants smoked, twice the general rate in Poland. The most common antiretroviral was tenofovir alafenamide, which is known to negatively affect lipids. Statins being prescribed at too low a dose or started too late, as well as diet and other lifestyle issues, may also have contributed to this finding.

As the PLWH population ages, CVD will become a greater concern, if LDL cannot be brought under control, study authors warned. They called for the development of unified, easy-to-use risk assessment tools specific to PLWH and uniform LDL levels among guidelines.

Hepatitis – in particular HBV and HCV – increases the risk of later cognitive dysfunction, and coinfection with HIV intensifies this danger, a modeling study published in AIDS found.

Notably, the study also found that early in the HIV epidemic, an AIDS diagnosis was also tied to cognitive dysfunction, but that the importance of such a diagnosis approached nil by the year 2000. Prior to the start of the combination antiretroviral therapy era in 1996, HIV intensified the interaction between age and executive domain function, according to the study; after antiretroviral therapy became widely available, however, HIV serostatus alone no longer appeared to affect the likelihood of cognitive problems.

The model was based on 804 participants (all men) in the U.S. Multicenter AIDS Cohort Study who had undergone neuropsychological testing in six cognitive domains. Among different cognitive dysfunction scales, researchers chose the Frascati cut-offs but called for future studies to determine the best set of criteria for this population.

While age was incorporated into the model, calendar time influenced predictive value, because the mix of available antiretrovirals, and thus their side effects, changed over time. Findings point to the need for additional research, including the effect of alcohol or drug use and specific antiretrovirals related to hepatitis, study authors concluded.