In the Journals

‘Start-up syndrome’ affects some Truvada users for short period

Study data suggest a small portion of new pre-exposure prophylaxis users experience gastrointestinal symptoms that could impact adherence, although these are largely resolved within 3 months of initiation.

“While well-tolerated overall, PrEP users have described a ‘start-up syndrome’ associated with [tenofovir disoproxil fumarate (TDF; Viread, Gilead Sciences)] and [emtricitabine/tenofovir disoproxil fumarate; (FTC/TDF; Truvada, Gilead Sciences)] of gastrointestinal (GI) and non-GI symptoms,” David V. Glidden, PhD, professor of biostatistics at the University of California, San Francisco, Robert M. Grant, MD, MPH, Betty Jean and Hiro Ogawa Endowed Investigator with the Gladstone Institutes in San Francisco, and colleagues wrote. “Side effects and poor tolerability have been associated with lower adherence in clinical settings in HIV treatment and HIV post-exposure prophylaxis, and may also influence PrEP adherence.”

Robert Grant

Robert M. Grant

iPrEX OLE: GI symptoms hamper PrEP adherence

To investigate this concern, the researchers reviewed data from the iPrEX open-label extension (OLE) trial, which examined uptake of and adherence to oral FTC/TDF among previously enrolled men who have sex with men and transgender women without HIV. For the first 3 months after PrEP initiation, and then quarterly for the remainder of the 18-month study, participants attended follow-up visits where study staff recorded the presence of GI and non-GI symptoms. For a subset of participants who were randomly assigned to the treatment arm during the study’s initial phase, further symptom reports for the same individuals under different conditions also were available for analysis. The researchers examined dried blood spots collected at each follow-up to measure participant adherence, and conducted ordinal logistic regression to identify associations between symptoms and adherence.

The researchers wrote that 1,225 participants chose to take FTC/TDF in the OLE, and 558 of them also had data available from initiating PrEP during the randomized phase of the trial. The proportion of OLE participants reporting PrEP-related symptoms increased an absolute 16% (95% CI, 13-19%) from baseline to 1 month; however, these largely declined to normal levels at 3 months for both GI and non-GI symptoms (P < .0001). These frequencies matched reports of nausea, GI illness or any symptoms recorded during the randomized phase, but varied during the first month by study site. While non-GI symptoms did not influence adherence (OR = 1.2; 95% CI, 0.4-3.7), GI symptoms within the first 4 weeks of initiation were associated with worsened adherence (OR = 0.47; 95% CI, 0.23-0.96) and were responsible for 7% (95% CI, 4-11%) of the cohort maintaining suboptimal PrEP adherence.

“Taken together, the findings of this analysis suggest that education and counseling should focus on the transient nature of a ‘start-up syndrome’ and advise PrEP users that the vast majority of those who do experience a ‘start-up syndrome’ successfully ‘overcome’ it within the first few months of PrEP use,” the researchers wrote.”

FTC/TDF efficacious among MSM, transgender women

Previous iPrEx OLE data reported by Grant and colleagues at the 2014 International AIDS Conference showed FTC/TDF to be efficacious and well-adhered to by those at higher risk for HIV infection.

Participants who took two or three tablets of the daily pill a week demonstrated an incidence rate of 0.6/100 person-years (95% CI, 0-2.5) — a 90% risk reduction over the 4.7/100 person-years (95% CI, 2.8-7.2) recorded among participants in whom the drug was not detected. No new infections occurred among those who took more than four tablets weekly (P < .0001).

Adherence of more than four tablets per week was greater among those at risk, according to the researchers, with reports of receptive anal sex without condoms associated with PrEP uptake (P = .001). In addition, there appeared to be no evidence of increased risk compensation, as the proportion of PrEP recipients who reported risky behavior decreased from 33% to 25% (P < .01) during the study period.

“Daily dosing of PrEP is recommended because it helps foster the habit of consistent PrEP use and increases drug levels in the body, providing the best safety cushion for individuals who occasionally miss doses,” Grant said in a press release. “At the same time, these results demonstrate that PrEP remains highly effective, even in real-world circumstances in which adherence may not be perfect.” – by Dave Muoio

Reference:

Grant RM. Abstract TUAC0105LB. Presented at: International AIDS Conference. July 20-25, 2014; Melbourne, Australia.

Disclosures: Glidden and Grant report relationships with ViiV Healthcare, a manufacturer of another investigational PrEP compound. Please see the full studies for a list of all other authors’ relevant financial disclosures.

Study data suggest a small portion of new pre-exposure prophylaxis users experience gastrointestinal symptoms that could impact adherence, although these are largely resolved within 3 months of initiation.

“While well-tolerated overall, PrEP users have described a ‘start-up syndrome’ associated with [tenofovir disoproxil fumarate (TDF; Viread, Gilead Sciences)] and [emtricitabine/tenofovir disoproxil fumarate; (FTC/TDF; Truvada, Gilead Sciences)] of gastrointestinal (GI) and non-GI symptoms,” David V. Glidden, PhD, professor of biostatistics at the University of California, San Francisco, Robert M. Grant, MD, MPH, Betty Jean and Hiro Ogawa Endowed Investigator with the Gladstone Institutes in San Francisco, and colleagues wrote. “Side effects and poor tolerability have been associated with lower adherence in clinical settings in HIV treatment and HIV post-exposure prophylaxis, and may also influence PrEP adherence.”

Robert Grant

Robert M. Grant

iPrEX OLE: GI symptoms hamper PrEP adherence

To investigate this concern, the researchers reviewed data from the iPrEX open-label extension (OLE) trial, which examined uptake of and adherence to oral FTC/TDF among previously enrolled men who have sex with men and transgender women without HIV. For the first 3 months after PrEP initiation, and then quarterly for the remainder of the 18-month study, participants attended follow-up visits where study staff recorded the presence of GI and non-GI symptoms. For a subset of participants who were randomly assigned to the treatment arm during the study’s initial phase, further symptom reports for the same individuals under different conditions also were available for analysis. The researchers examined dried blood spots collected at each follow-up to measure participant adherence, and conducted ordinal logistic regression to identify associations between symptoms and adherence.

The researchers wrote that 1,225 participants chose to take FTC/TDF in the OLE, and 558 of them also had data available from initiating PrEP during the randomized phase of the trial. The proportion of OLE participants reporting PrEP-related symptoms increased an absolute 16% (95% CI, 13-19%) from baseline to 1 month; however, these largely declined to normal levels at 3 months for both GI and non-GI symptoms (P < .0001). These frequencies matched reports of nausea, GI illness or any symptoms recorded during the randomized phase, but varied during the first month by study site. While non-GI symptoms did not influence adherence (OR = 1.2; 95% CI, 0.4-3.7), GI symptoms within the first 4 weeks of initiation were associated with worsened adherence (OR = 0.47; 95% CI, 0.23-0.96) and were responsible for 7% (95% CI, 4-11%) of the cohort maintaining suboptimal PrEP adherence.

“Taken together, the findings of this analysis suggest that education and counseling should focus on the transient nature of a ‘start-up syndrome’ and advise PrEP users that the vast majority of those who do experience a ‘start-up syndrome’ successfully ‘overcome’ it within the first few months of PrEP use,” the researchers wrote.”

FTC/TDF efficacious among MSM, transgender women

Previous iPrEx OLE data reported by Grant and colleagues at the 2014 International AIDS Conference showed FTC/TDF to be efficacious and well-adhered to by those at higher risk for HIV infection.

Participants who took two or three tablets of the daily pill a week demonstrated an incidence rate of 0.6/100 person-years (95% CI, 0-2.5) — a 90% risk reduction over the 4.7/100 person-years (95% CI, 2.8-7.2) recorded among participants in whom the drug was not detected. No new infections occurred among those who took more than four tablets weekly (P < .0001).

Adherence of more than four tablets per week was greater among those at risk, according to the researchers, with reports of receptive anal sex without condoms associated with PrEP uptake (P = .001). In addition, there appeared to be no evidence of increased risk compensation, as the proportion of PrEP recipients who reported risky behavior decreased from 33% to 25% (P < .01) during the study period.

“Daily dosing of PrEP is recommended because it helps foster the habit of consistent PrEP use and increases drug levels in the body, providing the best safety cushion for individuals who occasionally miss doses,” Grant said in a press release. “At the same time, these results demonstrate that PrEP remains highly effective, even in real-world circumstances in which adherence may not be perfect.” – by Dave Muoio

Reference:

Grant RM. Abstract TUAC0105LB. Presented at: International AIDS Conference. July 20-25, 2014; Melbourne, Australia.

Disclosures: Glidden and Grant report relationships with ViiV Healthcare, a manufacturer of another investigational PrEP compound. Please see the full studies for a list of all other authors’ relevant financial disclosures.