The study authors wrote that selection bias at transmission can shape HIV disease severity and tolerance in different groups.
For heterosexual individuals, transmitted HIV virulence is greater compared to men who have sex with men, according to a paper published in PLOS Pathogens.
Investigators from India conducted a meta-analysis and literature review of men-who-have-sex-with-men (MSM) and heterosexual individuals (HET) individuals with HIV in order to determine if there was more or less virulence in one group compared to the other and what contributing factors may be the root cause.
The study authors collected data from studies with more than 1000 participants that reported CD4 counts either at diagnosis or seroconversion in HET and MSM from 21 countries over 4 decades. The CD4 counts fall steeply, recover, then stabilize within a few weeks or months after the infection, the study authors described. These post-infection CD4 numbers are lower than the pre-infection state, they said, but CD4 count is an important indicator of the disease severity. When a CD4 count is lower, they said, the disease is more severe.
HET and MSM groups have little inter-mixing in most geographic regions, the investigators wrote, which presents an opportunity for studying the virulence of fitter transmitted/founder (T/F) strains. The study authors also noted that anal intercourse is more than 10-fold more permissive on average compared to penile/vaginal intercourse. For example, among HET groups, men had T/F viruses with higher predicted fitness in vivo compared to women, which reinforced the investigators’ hypothesis regarding the difference in transmission modes between the MSM and HET groups.
HET groups had a consistently lower CD4 count compared to MSM, the study authors found. Additionally, they observed that while the effect sizes varied across studies, there were no large studies they found that reported higher early CD4 cell counts in HET groups compared to MSM groups, they wrote.
MSM may be viewed as more tolerant to T/F strains than HET groups, the study authors said, defining that as a host that does not suffer the disease despite high pathogen load. Other examples of tolerant groups, according to the study authors, include HIV-1-infected viremic non-progressors, HIV-1-infected children, and SIV-infected sooty mangabeys.
Some contributing factors to this tolerance could be timing of onward transmission, diagnosis delay, HIV-1 subtype, ethnicity, sex, and age, the study authors suggested. Upon further examination from the published literature, the investigators observed that early transmissions are more common among MSM than HET, where MSM formed larger transmission clusters than HET.
Diagnosing times could be similar, but MSM may not get diagnosed earlier than HET. Regardless, the study authors wrote that diagnosis delay appeared not to be a major factor.
Additionally, in China and the US, MSM and HET have similar ethnicities but risk on the group outcome is lower in MSM than HET. In Europe, MSM are primarily Caucasian and about a third of infected HET are sub-Saharan African origin, they said. These CD4 count differences did not display any effect of ethnicity on risk on the group outcome. Age and sex could produce confounding effects, the study authors added.
“Because different risk groups tend to use different predominant modes of transmission, it is possible that the T/F strains of HIV-1, directly affected by the bottlenecks, may have evolved differently in the different groups,” the study authors concluded. “Our study shows, for the first time, that the selection bias at transmission is an important underlying factor shaping HIV-1 adaptation at the population level. The reduction in CD4 cell counts early in infection was substantially higher in HET than MSM, consistent with the more stringent selection at transmission resulting in more virulent T/F strains in HET than MSM.”