Assessing the uncertainty around age-mixing patterns in HIV transmission inferred from phylogenetic trees.

Understanding age-mixing patterns in Human Immunodeficiency Virus (HIV) transmission networks can enhance the design and implementation of HIV prevention strategies in sub-Saharan Africa. Due to ethical consideration, it is less likely possible to conduct a benchmark study to assess which sampling strategy, and sub-optimal sampling coverage which can yield best estimates for these patterns. We conducted a simulation study, using phylogenetic trees to infer estimates of age-mixing patterns in HIV transmission, through the computation of proportions of pairings between men and women, who were phylogenetically linked across different age groups (15-24 years, 25-39 years, and 40-49 years); and the means, and standard deviations of their age difference. We investigated also the uncertainty around these estimates as a function of the sampling coverage in four sampling strategies: when missing sequence data were missing completely at random (MCAR), and missing at random (MAR) with at most 30%-50%-70% of women in different age groups being in the sample. The results suggested that age-mixing patterns in HIV transmission can be unveiled from proportions of phylogenetic pairings between men and women across age groups; and the mean, and standard deviation of their age difference. A 55% sampling coverage was sufficient to provide the best values of estimates of age-mixing patterns in HIV transmission with MCAR scenario. But we should be cautious in interpreting proportions of men phylogenetically linked to women because they may be overestimated or underestimated, even at higher sampling coverage. The findings showed that, MCAR was the best sampling strategy. This means, it is advisable not to use sequence data collected in settings where we can find a systematic imbalance of age and gender to investigate age-mixing in HIV transmission. If not possible, ensure to take into consideration the imbalance in interpreting the results.