Impact of chemorophylaxis policy for AIDS-immunocompromised patients on emergence of bacterial resistance

Abstract

Chemoprophylaxis (antibiotic prophylaxis) is a long relied-upon means of opportunistic infection management among HIV/AIDS patients, but its use represents an evolutionary tradeoff: Despite the benefits of chemoprophylaxis, widespread use of antibiotics creates a selective advantage for drug-resistant bacterial strains. Especially in the developing world, with combined resource limitations, antibiotic misuse, and often-poor infection control, the emergence of antibiotic resistance may pose a critical health risk. Extending previous work that demonstrated that this risk is heightened when a significant proportion of the population is HIV/AIDS-immunocompromised, we work to address the relationship between HIV/AIDS patients' use of antibiotic chemoprophylaxis and the emergence of resistance. We apply an SEIR compartmental model, parameterized to reflect varying percentages of chemoprophylaxis use among HIV/AIDS+ patients in a resource-limited setting, to investigate the magnitude of the risk of prophylaxis-associated emergence versus the individual-level benefits it is presumed to provide. The results from this model suggest that, while still providing tangible benefits to the individual, chemoprophylaxis is associated with negligible decreases in population-wide morbidity and mortality from bacterial infection, and may also fail to provide assumed efficacy in reduction of TB prevalence.

Impact of Strain Competition on Bacterial Resistance in Immunocompromised Populations

“…Both the emergence of antibiotic resistance and the vulnerability of the HIV/AIDS-immunocompromised to opportunistic pathogens are well-documented medical crises [7,[19][20][21][22][23][24][25]. In modeling the interplay between these two health risks, we recently demonstrated that the disrupted selective pressures associated with an HIV/AIDS-related host immunosuppression create the potential for a drastic, AIDS-attributable increase in the novel emergence of drug resistance [10].…”

“…While there is a slight fitness-dependent change in the ratio of drug-sensitive to drug-resistant infections, the rapid q-strain dominance occurs even when its comparative fitness is low. Therefore, surveillance efforts that analyze total tuberculosis (TB) prevalence only, while failing to consider the percentage of resistant strain infectives within the population, could be critically flawed-especially when HIV/AIDS prevalence is high [10].…”

“…In our previous works [8,10], we made the simplifying assumption that antibiotic-resistant infections, while originating via the emergence of drug-resistant mutations, increase in prevalence solely due to selective pressures within the host population. However, these same selective advantages can lead to resistant strain dominance, which in turn leads to a greater percentage of infectives harboring and transmitting pathogens that are nonresponsive to antibiotics [11].…”

“…Moreover, factors such as a limited understanding of HIV transmission, high-risk sexual behavior (sometimes in conjunction with intravenous drug use), and inconsistent access to highly active antiretroviral therapy (HAART) once seropositive, currently place developing nations in danger of increasing HIV/AIDS prevalence [13,14]. The combination of these factors enhances the risk of the emergence of antibiotic resistance [10] and this risk could be compounded by resistant strain circulation. To reflect these conditions accurately, we have chosen Swaziland (also now called the Kingdom of Eswatini; a nation in southern Africa) as a model population.…”

“…To explore the evolutionary and epidemiological effects of the emergence and subsequent circulation of antibiotic-resistant pathogens within a highly immunocompromised host population, we present an SEIR model [17], and parameterize it to reflect conditions similar to those in Swaziland (as in [8,10]). We vary the percentage of HIV/AIDS+ susceptibles using antibiotic prophylaxis (thereby protecting themselves from drug-sensitive pathogens), and the probability of resistant strain transmission, including the potential for either increased or decreased fitness of the resistant strain, relative to that of the wild-type.…”