Perspective

Researchers identify first known case of PrEP failure in developing country

A 28-year-old man in Thailand appeared to have acquired multidrug-resistant HIV while on pre-exposure prophlyaxis, or PrEP, researchers reported.

It is one of the few cases of PrEP failure with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and the first known reported case in a developing country, according to Donn J. Colby, MD, of the Thai Red Cross AIDS Research Center in Bangkok, and colleagues.

Two reports previously published in The New England Journal of Medicine and the Journal of Acquired Immune Deficiency Syndromes detailed separate cases of multidrug-resistant (MDR) HIV-1 acquisition in the presence of PrEP. Both cases were men who have sex with men in North America whose adherence to PrEP was confirmed by adequate FTC and TDF concentrations in hair and blood samples.

The current report, published in Clinical Infectious Diseases, describes the case of a sex worker in Pattaya, Thailand, who started PrEP with FTC/TDF in March 2016. The patient was tested for HIV with a third-generation (3rdG) antibody test before starting PrEP and 5 weeks after PrEP initiation. Results indicated the patient was not infected. After 8 weeks of PrEP use, the patient was tested again with a different 3rdG test, which was also nonreactive. However, when the same sample was tested with a qualitative HIV-RNA test, results came back positive, prompting a referral for evaluation and treatment. His viral load was 116,187 copies/mL.

The patient reported participating in several events of condomless anal intercourse with a foreign male client in the first 2 weeks of PrEP initiation. Before starting PrEP, the patient said he used condoms during all anal intercourse events within the past 2 months.

An analysis of FTC/TDF levels in hair samples suggested the patient was adherent to PrEP in the preceding 6 weeks, according to the researchers. In addition, a plasma sample obtained shortly after the last reported PrEP dose was also indicative of consistent adherence.

Genotypic resistance testing showed the patients’ virus had an M184V mutation conferring high-level resistance to FTC. The researchers identified two other mutations — A98G and K103N — with resistance to first-generation non-nucleoside reverse-transcriptase inhibitors.

After discontinuing TDF/FTC, the patient’s physicians prescribed him a combination regimen of zidovudine, lamivudine and lopinavir/ritonavir. His viral load decreased to less than 20 copies/mL after 8 weeks of ART.

Colby and colleagues said it is possible that the patient contracted HIV during the first week of PrEP use, before the drugs were fully effective. Owing to limited data, however, the exact timing of HIV acquisition remains unclear.

“Although HIV-1 transmission before PrEP use cannot be ruled out, the history of high-risk behavior only after PrEP use started, the fact that 3rdG HIV-1 antibody test results remained nonreactive after 5 weeks of PrEP, and the high viral load at first measurement after 8 weeks of PrEP all argue against the presence of HIV-1 infection at PrEP initiation,” the researchers wrote.

They concluded that this case, along with the two other previously reported cases, demonstrates that MDR HIV-1 can be acquired while patients are consistently taking PrEP.

“Providers prescribing PrEP and individuals taking TDF/FTC should be aware of this risk,” they wrote. – by Stephanie Viguers

References:

Colby DJ, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy321.

Knox DC, et al. N Engl J Med. 2017;doi:10.1056/NEJMc1611639.

Markowitz M, et al. J Acquir Immune Defic Syndr. 2017;doi:10.1097/QAI.0000000000001534.

Disclosures: Colby reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

A 28-year-old man in Thailand appeared to have acquired multidrug-resistant HIV while on pre-exposure prophlyaxis, or PrEP, researchers reported.

It is one of the few cases of PrEP failure with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and the first known reported case in a developing country, according to Donn J. Colby, MD, of the Thai Red Cross AIDS Research Center in Bangkok, and colleagues.

Two reports previously published in The New England Journal of Medicine and the Journal of Acquired Immune Deficiency Syndromes detailed separate cases of multidrug-resistant (MDR) HIV-1 acquisition in the presence of PrEP. Both cases were men who have sex with men in North America whose adherence to PrEP was confirmed by adequate FTC and TDF concentrations in hair and blood samples.

The current report, published in Clinical Infectious Diseases, describes the case of a sex worker in Pattaya, Thailand, who started PrEP with FTC/TDF in March 2016. The patient was tested for HIV with a third-generation (3rdG) antibody test before starting PrEP and 5 weeks after PrEP initiation. Results indicated the patient was not infected. After 8 weeks of PrEP use, the patient was tested again with a different 3rdG test, which was also nonreactive. However, when the same sample was tested with a qualitative HIV-RNA test, results came back positive, prompting a referral for evaluation and treatment. His viral load was 116,187 copies/mL.

The patient reported participating in several events of condomless anal intercourse with a foreign male client in the first 2 weeks of PrEP initiation. Before starting PrEP, the patient said he used condoms during all anal intercourse events within the past 2 months.

An analysis of FTC/TDF levels in hair samples suggested the patient was adherent to PrEP in the preceding 6 weeks, according to the researchers. In addition, a plasma sample obtained shortly after the last reported PrEP dose was also indicative of consistent adherence.

Genotypic resistance testing showed the patients’ virus had an M184V mutation conferring high-level resistance to FTC. The researchers identified two other mutations — A98G and K103N — with resistance to first-generation non-nucleoside reverse-transcriptase inhibitors.

After discontinuing TDF/FTC, the patient’s physicians prescribed him a combination regimen of zidovudine, lamivudine and lopinavir/ritonavir. His viral load decreased to less than 20 copies/mL after 8 weeks of ART.

Colby and colleagues said it is possible that the patient contracted HIV during the first week of PrEP use, before the drugs were fully effective. Owing to limited data, however, the exact timing of HIV acquisition remains unclear.

“Although HIV-1 transmission before PrEP use cannot be ruled out, the history of high-risk behavior only after PrEP use started, the fact that 3rdG HIV-1 antibody test results remained nonreactive after 5 weeks of PrEP, and the high viral load at first measurement after 8 weeks of PrEP all argue against the presence of HIV-1 infection at PrEP initiation,” the researchers wrote.

They concluded that this case, along with the two other previously reported cases, demonstrates that MDR HIV-1 can be acquired while patients are consistently taking PrEP.

“Providers prescribing PrEP and individuals taking TDF/FTC should be aware of this risk,” they wrote. – by Stephanie Viguers

References:

Colby DJ, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy321.

Knox DC, et al. N Engl J Med. 2017;doi:10.1056/NEJMc1611639.

Markowitz M, et al. J Acquir Immune Defic Syndr. 2017;doi:10.1097/QAI.0000000000001534.

Disclosures: Colby reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    David C. Knox

    David C. Knox

    Access to TDF/FTC for HIV PrEP is expanding globally. I am reassured that of the estimated 200,000 people using TDF/FTC globally for PrEP, there have been only a few reported cases of HIV acquisition despite adherence to TDF/FTC. These infrequent case reports of HIV seroconversion while on PrEP should not discourage patients from accessing PrEP or health care professionals from prescribing PrEP in high-risk individuals. Patients who seroconvert while on PrEP require immediate linkage to care with an experienced HIV care provider for investigation of potential transmitted or acquired drug resistance and ART initiation.

    • David C. Knox, MD
    • Staff HIV Primary Care Physician Maple Leaf Medical Clinic, Toronto

    Disclosures: Knox reports no relevant financial disclosures.