This Week in HIV Research: Can Vaginal Microbiome Affect HIV Drug Levels?

This week, a study examines how the vaginal microbiome may affect antiretroviral concentrations in the genital tract. In other research news, we read about the potential impact of global supply-chain interruptions on HIV drug resistance, and we also get a glimpse of an intriguing mystery regarding the number of latently HIV-infected CD4 cells in different global populations.

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Concentrations of Oral Antiretrovirals Differ by Vaginal Microbiome

Antiretroviral concentrations in women's genital tracts differ among vaginal microbiomes, a proof-of-principle study published in The Journal of Infectious Diseases found.

Researchers analyzed the bacterial environment and drug concentrations of 20 women across one menstrual cycle each. All participants took tenofovir disoproxil fumarate/emtricitabine (Truvada) and ritonavir-boosted atazanavir (Reyataz), and were virally suppressed. Almost all were African American.

Antiretroviral concentrations were lower in women whose vaginal microbiome was dominated by Lactobacillus compared to those with more diverse bacteria. The effect of different pH levels within microbiomes on the medications and/or the interaction of certain Lactobacillus species with tenofovir may help explain the results, study authors hypothesized.

While the findings need to be corroborated in larger trials, researchers noted that differences in concentrations of oral drugs based on vaginal microbiota may impact pre-exposure prophylaxis (PrEP) for women. That said, another study recently found that bacterial vaginosis -- an overabundance of anaerobic bacteria in the vagina --- does not reduce the efficacy of oral PrEP.

Global Supply Chain Problems Contribute to Rise of HIV Drug Resistance

Low or no stock of specific antiretrovirals contributes to the rise of drug-resistant HIV in low- and middle-income countries, researchers from the U.S. Agency for International Development argued in The Journal of Infectious Diseases.

Surveys have shown that running out of specific medications is much more common in parts of sub-Saharan Africa than in other regions of the world. In addition, clinics may dispense two-week supplies instead of monthly supplies to deal with insufficient stock, requiring people living with HIV to make additional trips -- often over long distances -- for their medications. HIV treated with non-nucleoside reverse transcriptase inhibitors -- the most common first-line treatment -- is especially susceptible to developing resistance when the drugs are stopped.

Antiretroviral shortages are partly the result of complex global supply chains that often require clinics to estimate their drug needs 9 to 12 months in advance, the authors wrote, adding that laboratory work is beset by similar logistical problems, which may be exacerbated by equipment problems. They called for improved forecasting and strengthened laboratory supply chains to meet these challenges.

Fewer Latently Infected CD4 Cells in Ugandans Than in Americans

Virally suppressed Ugandans had significantly fewer latently infected resting CD4 cells than a similar group of Americans, researchers reported in Clinical Infectious Diseases.

Both cohorts started antiretroviral therapy during chronic infection with HIV. Latent infection with replication-competent virus was 3-fold lower among the 70 Ugandans tested compared to a group previously observed in Baltimore, Maryland. In Uganda, the longer people were virally suppressed, the lower their number of CD4 cells harboring latent virus.

It is unclear whether Ugandans' smaller HIV reservoir is due to fewer cells being infected or to these cells decaying more rapidly. While HIV-1 subtypes differed between the two groups, the most common subtype in the African cohort is genetically very similar to the most common U.S. subtype. Study authors therefore did not believe that this difference explains the results.

"The biological mechanism driving the observed smaller reservoir in Ugandans could not be identified in this study but may be of significance to HIV-1 eradication efforts," they concluded.