Seroconversion Following Nonoccupational Postexposure Prophylaxis against HIV

University of California, San Francisco, San Francisco, California, United States
Clinical Infectious Diseases (Impact Factor: 8.89). 12/2005; 41(10):1507-13. DOI: 10.1086/497268
Source: PubMed

ABSTRACT The efficacy of antiretroviral postexposure prophylaxis (PEP) against infection with human immunodeficiency virus (HIV) following occupational exposures has prompted the use of PEP after nonoccupational exposures. There are, however, important differences between occupational and nonoccupational exposures, and the effectiveness of PEP following nonoccupational exposure is unknown. We sought to describe the occurrence and circumstances of HIV seroconversion following nonoccupational PEP.
HIV uninfected individuals reporting potential sexual or injection drug use exposures to HIV in the preceding 72 h received a 28-day regimen of antiretroviral therapy and counseling in a nonrandomized trial. The level of HIV antibody was measured 12 weeks after PEP initiation.
Of 877 exposed subjects, 702 were evaluable 12 weeks after exposure. Seroconversion was detected in 7 subjects (1%; 95% confidence interval, 0.4%-2%). Three seroconverters reported having no exposures after PEP initiation and, thus, probably represent evidence of chemoprophylactic failure. In the other 4 subjects, additional exposures to HIV after PEP initiation or detection of HIV RNA in plasma specimens obtained at baseline precluded determination of the source of seroconversion. No exposure source was available to assess genetic concordance with the seroconverter's virus.
As for occupational exposure, PEP is not completely effective in preventing HIV infection following nonoccupational exposure. Therefore, primary prevention remains essential. In contrast to the occupational setting, the potential source of exposure is rarely available for testing in the nonoccupational setting, and exposures are often not isolated. Thus, it is often impossible to determine whether seroconversion resulted from failure of PEP or from other exposures, posing difficulties for future comparative studies seeking to evaluate the effectiveness of PEP.

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Available from: Barbara Shacklett, Sep 25, 2015
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    • "In rhesus macaque studies investigating oral FTC/TDF PrEP, breakthrough infections following rectal exposure showed FTC-selected DR mutations M184V/I [15]. In people with unrecognized infection, antiretroviral use intended as PrEP is functionally postexposure prophylaxis (PEP), where DR can occur in breakthrough systemic infection [2–4, 16, 17]. Additionally, initial efforts administering single-dose nevirapine to mothers at birth for prevention of mother-to-child-transmission (MTCT) resulted in rapid emergence of drug-selected mutations in infected infants measured by population sequencing [18–22]. "
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    ABSTRACT: Background: The iPrEx study demonstrated that combination oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis (PrEP) protects against HIV acquisition in men who have sex with men and transgender women. Selection for drug resistance could offset PrEP benefits. Methods: Phenotypic and genotypic clinical resistance assays characterized major drug resistant mutations. Minor variants with FTC/TDF mutations K65R, K70E, M184V/I were measured using 454 deep sequencing and a novel allele-specific polymerase chain reaction (AS-PCR) diagnostic tolerant to sequence heterogeneity. Results: Control of primer-binding site heterogeneity resulted in improved accuracy of minor variant measurements by AS-PCR. Of the 48 on-study infections randomized to FTC/TDF, none showed FTC/TDF mutations by clinical assays despite detectable drug levels in 8 participants. Two randomized to FTC/TDF had minor variant M184I detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only 1 of which had low but detectable drug levels. Among those with acute infection at randomization to FTC/TDF, M184V or I mutations that were predominant at seroconversion waned to background levels within 24 weeks after discontinuing drug. Conclusions: Drug resistance was rare in iPrEx on-study FTC/TDF-randomized seroconverters, and only as low-frequency minor variants. FTC resistance among those initiating PrEP with acute infection waned rapidly after drug discontinuation. Clinical Trials Registration.NCT00458393.
    The Journal of Infectious Diseases 04/2014; 210(8). DOI:10.1093/infdis/jiu233 · 6.00 Impact Factor
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    • "These included nurses who were comfortable with sexual assault and HIV issues, proactive follow-up, financial support for transportation, and flexible follow-up locations. The only literature reporting high follow-up rates are prospective studies and a study describing another proactive follow-up system in Amsterdam [32–34]. It is important to consider the resources required to provide comprehensive follow-up services when deciding to develop systems to initiate PEP. "
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    ABSTRACT: We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition.
    AIDS and Behavior 02/2011; 16(4):990-8. DOI:10.1007/s10461-011-9892-3 · 3.49 Impact Factor
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    • "Following extensive public and political debate, the South African Government adopted a policy in 2002 to provide anti-retroviral medication to prevent HIV transmission as part of comprehensive post-sexual assault care (South African Department of Health, 2005). There is no direct evidence of the efficacy of post-exposure prophylaxis (PEP) for sexual exposure, but studies on animals, on occupational exposures and prevention of mother-to-child transmission suggest that PEP is highly effective if commenced within 72 hours of exposure and 28 days of uninterrupted prophylaxis are completed (Roland et al., 2005). Based on this research, South Africa adopted the use of dual therapy with both Lamivudine and Zidovudine, and in some provinces triple therapy is given with inclusion of Kaletra for ''high risk'' cases. "
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    ABSTRACT: South Africa has one of the highest rates of both rape and HIV infections. Of great concern is the possibility of HIV transmission during the assault, but adherence to post-exposure prophylaxis (PEP) has been varied and low. We developed a telephonic psycho-social support, leaflet and adherence diary intervention for rape victims and tested its impact on adherence to PEP. A randomised control trial was conducted in the Western and Eastern Cape and 279 rape survivors were enrolled in two arms. The intervention involved the providing of an information leaflet including an adherence diary and follow-up support through telephone calls by a counsellor during the 28 days of taking the PEP. The controls received the leaflet. Follow-up interviews and tablet checks were done with 253 participants to assess adherence. The primary outcome was completion of 28 days of PEP with no more than three missed doses (94% adherence). There was more adherence in the intervention arm (38.2% vs. 31.9%), but the estimated intervention effect of 6.5% (95% CI: -4.6 to 17.6%) was not statistically significant, p=0.13. The intervention was associated with the reading of the pamphlet (p=0.07) and an increased use of the diary (p=0.01), but did not reduce depressive psychopathology. Overall adherence was greater amongst those who read the leaflet and used the medication diary. The study showed that the intervention was not effective in significantly improving adherence and adherence levels were low in both study arms. Further research to understand reasons for non-adherence is needed before further interventions are developed.
    AIDS Care 10/2010; 22(10):1173-81. DOI:10.1080/09540121003692185 · 1.60 Impact Factor
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