Management of occupational and nonoccupational postexposure HIV prophylaxis

The principles of managing patients with recent HIV exposure are similar whether the exposure occurs in an occupational or nonoccupational setting. For both settings, clinicians should assess the likelihood that HIV and other bloodborne viruses will be transmitted as a consequence of the exposure; advise the patient about the risks and benefits of treatment; choose an appropriate antiretroviral treatment regimen (if the decision is made to treat); screen for other illnesses that may complicate treatment or follow-up; counsel patients about the importance of adhering to treatment; promote safe-sex practices and methods to avoid future exposures; follow the patient for potential side effects of treatment; and provide follow-up care including repeat HIV testing for seroconversion, surveillance for primary HIV infection, and reinforcement of counseling messages.     

The public health impact of widespread availability of nonoccupational postexposure prophylaxis against HIV

OBJECTIVE: The aim of the study was to describe the use of nonoccupational postexposure prophylaxis (NPEP) in Australia, and to estimate the number of HIV infections that its use prevented. METHODS: We conducted a population-based observational cohort study of people who presented to antiretroviral prescribers in Eastern Australia, and reported a high-risk nonoccupational exposure to HIV, in 1998-2004. Prescribers collected data at baseline, 4 weeks and 6 months. Data collected included details of HIV exposure, drug regimens and HIV serostatus. RESULTS: The great majority of the 1601 participants were male (95%) and presented after male homosexual exposure (87%). Only 32% of exposures were to HIV-positive sources. Two antiretroviral drugs were prescribed after 48% of events, and three or more drugs after 52% of events. The median time to receipt of NPEP was 23 h. Side effects were reported by 66% of participants. No case of NPEP failure in an adherent individual was identified. It was estimated that 0.9-9.2 HIV infections had been prevented. This compared with a total of 1138 newly acquired HIV infections notified in the geographical area covered by the study. CONCLUSIONS: In Australia, NPEP has been widely prescribed and is mainly targeted at high-risk exposures. Although there were no identified failures of NPEP, it is likely that only a small proportion of new HIV infections in the study area were prevented. NPEP may be a valuable preventive intervention for an individual, but it can only play a minor role in HIV prevention at the population level unless targeting can be further improved.     

Cost-effectiveness of HIV nonoccupational post-exposure prophylaxis in Australia

Objective

The aim of the study was to determine the cost‐effectiveness of HIV nonoccupational post‐exposure prophylaxis (NPEP) in Australia.

Methods

A retrospective cost analysis of a population‐based observational cohort of 1601 participants eligible for NPEP in Australia between 1998 and 2004 was carried out. We modelled NPEP treatment costs and combined them with effectiveness outcomes to calculate the cost per seroconversion avoided. We estimated the cost‐utility of the programme, and sensitivity and threshold analysis was performed on key variables.

Results

The average NPEP cost per patient was A$1616, of which A$848 (52%) was for drugs, A$331 (21%) for consultations, A$225 (14%) for pathology and A$212 (13%) for other costs. The cost per seroconversion avoided in the cohort was A$1 647 476 in our base case analysis, and A$512 410 when transmission rates were set at their maximal values. The cost per quality‐adjusted life‐year (QALY) was between A$40 673 and A$176 772, depending on the risks of HIV transmission assumed.

Conclusions

In our base case, NPEP was not a cost‐effective intervention compared with the widely accepted Australian threshold of A$50 000 per QALY. It was only cost‐effective after receptive unprotected anal intercourse exposure to an HIV‐positive source. Although NPEP was a relatively well‐targeted intervention in Australia, its cost‐effectiveness could be improved by further targeting high‐risk exposures.     

Prescribing practices in a population-based HIV postexposure prophylaxis program

OBJECTIVES: To characterize factors associated with being prescribed triple or double postexposure prophylaxis (PEP) against HIV in a population-based program. METHODS: Individuals potentially exposed to HIV received a 5 day starter kit of either double or triple antiretroviral PEP between April 1999 and November 2000 and did/did not receive the remaining 23 days PEP. Data were collected through dispensation of kits. Logistic regression identified characteristics independently associated with being prescribed triple therapy starter kits and with any 23 day follow-up. RESULTS: Of 2064 people receiving 5 day PEP [403 (20%) triple and 1661 (80%) double], 590 (29%) received 23 day follow-up. Independently associated with being prescribed triple therapy starter kits were being male [adjusted odds ratio (AOR) 1.38; 95% confidence interval (CI) 1.10-1.74; P = 0.006), occupational mucocutaneous injuries (AOR 1.70; 95% CI, 1.14-2.55; P = 0.010), and community needlesticks (AOR 2.04; 95% CI, 1.54-2.69; P < 0.001). Independently associated with being prescribed the 23 day follow-up were being male (AOR 1.24; 95% CI, 1.00-1.53; P = 0.04), community mucocutaneous incidents (AOR 2.83; 95% CI, 1.41-5.70; P = 0.004), community needlesticks (AOR 1.75; 95% CI, 1.33-2.29; P < 0.001), and having received triple therapy as the starter kit (AOR 2.61; 95% CI, 2.07-3.29; P < 0.001). CONCLUSIONS: Being prescribed triple therapy starter PEP was associated with being male and with experiencing an occupational mucocutaneous or community needlestick injury. Receiving the remaining 23 days PEP was associated with being male, experiencing a community mucocutaneous or needlestick injury, and triple therapy as the initial 5 day starter PEP.     

Antiretrovirals to prevent HIV infection: Pre-and postexposure prophylaxis

More than 3 million people are now receiving antiretroviral therapy (ART) worldwide. Currently, the indications for ART depend primarily on CD4 count, blood viral burden, and clinical signs and symptoms suggesting advanced HIV disease. However, interest is increasing in ART’s preventive potential. Postexposure prophylaxis following both occupational and nonoccupational exposure to HIV is the standard-of-care in many settings. Observational and ecologic studies suggest that ART administered to HIV-infected people reduces transmission within serodiscordant couples. Pre-exposure prophylaxis to prevent HIV infection is a potentially safe and intermittent intervention for very high-risk people, and clinical trials to evaluate this preventive strategy are underway. The prevention benefits of ART may begin to affect the decision of when to start therapy and add a much-needed strategy to current HIV prevention efforts.     

Occupational postexposure prophylaxis for HIV: The PEPline perspective

Transmission of HIV through occupational exposure in healthcare personnel is rare. Risk of transmission from an HIV-infected source person is estimated at 0.3% for percutaneous exposures and 0.09% for mucous membrane or nonintact skin exposures, with risk modulated by exposure and source-patient characteristics. Counseling on risk assessment, postexposure prophylaxis (PEP), and baseline and follow-up testing after exposure is provided through PEPline, the National Clinicians' Post-Exposure Prophylaxis Hotline. PEPline receives approximately 900 calls per month, most from treating clinicians. HIV PEP consists of a 28-day course of a basic or an expanded regimen, depending on the severity or volume of exposure and HIV infection characteristics of the source person. An update to the 2005 US Department of Health PEP drug recommendations is expected in 2011. This article summarizes a lecture given by Ronald H. Goldschmidt, MD, at the 13th Annual Ryan White HIV-AIDS Program Clinical Conference held in August 2010 in Washington, DC.     

Predictors of the initiation of HIV postexposure prophylaxis in Rhode Island emergency departments

The objective of this study was to elucidate factors that predicted the initiation of HIV postexposure prophylaxis (PEP) for blood or body fluid exposures evaluated at Rhode Island emergency departments (EDs). The study involved a retrospective review of patient visits to all civilian Rhode Island EDs for these exposures from 1995 to mid-2001. Multivariate logistic regression models were created to evaluate predictors of the offering and the acceptance and receipt of HIV PEP from 1996 to 2001. The search identified 3622 patients who sustained a blood or body fluid exposure. Of these, 43.8% were health care workers (HCWs) and 57.2% were not HCWs. Most (52.0%) of the exposures were nonsexual. HIV PEP was offered to 21.0% and accepted and received by 9.4% of all patients. HIV PEP was offered more often after significant exposures, exposures to known HIV-infected sources, when time elapsed after the exposure was shorter, if the patients were HCWs, adults, presented to a teaching hospital, presented during the latter years of the study, or sustained nonsexual exposures. Once offered HIV PEP, patients who were male, adult, sustained a significant exposure, knew the source was HIV infected, sustained a nonsexual exposure, or were HCWs had a greater odds of accepting and receiving HIV PEP. Even when controlling for exposure significance, HIV status, and time elapsed since the exposure, several factors such as gender and type of hospital that are unrelated to the exposure appeared to influence the initiation of HIV PEP. ED providers should ensure that these factors do not inappropriately restrict its initiation.     

The use of a triple nucleoside-nucleotide regimen for nonoccupational HIV post-exposure prophylaxis

OBJECTIVES: Nonoccupational post-exposure prophylaxis (NPEP) for HIV is recommended after high-risk sexual exposure. Because of the high incidence of intolerable side effects observed with protease inhibitor- and zidovudine-based NPEP regimens, our unit changed standard NPEP treatment to 28 days of tenofovir-lamivudine-stavudine (TDF-3TC-d4T). The aim of this study was to compare side effects and numbers of individuals completing NPEP before and after this change. METHODS: Parameters were compared amongst individuals commencing the following NPEP regimens: zidovudine-lamivudine (ZDV-3TC), zidovudine-lamivudine-nelfinavir (ZDV-3TC-NFV) and TDF-3TC-d4T. RESULTS: A total of 385 individuals received ZDV-3TC (n = 36), ZDV-3TC-NFV (n = 225) or TDF-3TC-d4T (n = 137) as NPEP for the first time between June 1999 and November 2003. Noncompletion rates were 25%, 32% and 15%, respectively (P = 0.001), with odds ratios for noncompletion being 2.0 [95% confidence interval (CI) 0.8-4.8] and 2.7 (95% CI 1.6-4.8) in the first two groups compared with the TDF-3TC-d4T group (P = 0.008). Adverse events were less common in the TDF-3TC-d4T group, with significantly lower rates of nausea and headache, but significantly higher rates of peripheral neuropathy and asymptomatic raised transaminases. There was no HIV seroconversion in any group. CONCLUSIONS: TDF-3TC-d4T is significantly better tolerated than ZDV-3TC or ZDV-3TC-NFV as NPEP and results in greater numbers of individuals completing 28 days of treatment.     

Nonoccupational HIV postexposure prophylaxis: a new role for the emergency department

Despite numerous primary prevention campaigns, new cases of HIV infection are occurring at high rates. Postexposure prophylaxis (PEP) after possible HIV exposures from sexual encounters or injection drug use may prove to be a worthwhile means of reducing HIV infection. Although there are no studies that directly demonstrate its efficacy, indirect support comes from animal and human studies. Multiple animal studies have shown that antiretroviral medications can reduce simian immunodeficiency virus infections if given early and for a prolonged period. A study of health care workers suggests that zidovudine taken after needlestick injuries can dramatically reduce HIV seroconversion. Zidovudine and nevirapine use recently showed great reductions in perinatal HIV transmission. Studies of dendritic and T-cell processing of simian immunodeficiency virus and HIV indicate that antiretroviral medications taken soon after a viral exposure may terminate viral replication. Regimens of 2 or 3 antiretroviral medications have been suggested as prophylactic measures after certain exposures. Even though limited experience exists with these populations, HIV PEP is most likely safe in pregnancy and for children. Emergency departments are encouraged to anticipate the probable demands for nonoccupational HIV PEP by establishing protocols for its rapid provision and ensuring proper follow-up care.     

A review of HIV postexposure prophylaxis provision at a genitourinary medicine department

We undertook a retrospective case-note audit of all patients who presented to the Edinburgh genitourinary (GU) medicine department following a potential exposure to HIV infection during the period 1 January 2006 to 31 December 2008. Over the audit period, 81 individuals attended the department, in relation to 85 exposure events. Twenty-three (27%) exposures had occurred in a health-care occupational setting and 50 (59%) in a sexual context. Baseline HIV testing was only performed in 38 (45%) of the 85 exposures. Postexposure prophylaxis (PEP) was initiated in 65 (76%) cases: 61 (94%) received the first dose within the recommended 72 hours. In 68 (80%) of the 85 exposures, the PEP initiation decision tallied with guideline recommendations. Fifty-six of the 65 individuals started on PEP continued beyond 72 hours; 53 of them were reviewed at least once during the course of PEP and had routine blood monitoring performed. Documentation regarding adherence was poor, with only 31 having this recorded in notes. Thirty-seven (66%) individuals who continued on PEP attended for follow-up HIV testing at three months. In summary, the department performed well in some aspects of PEP provision. However, baseline HIV testing and documentation regarding adherence are unsatisfactory and we suggest recommendations to improve this.