Post-Exposure Prophylaxis

“Postexposure prophylaxis (PEP) for HIV is recommended by international, national, and state guidelines, but implementation among sexual assault survivors is challenging…From September 2003 through January 2005, 1103 individuals (97% women) were evaluated for PEP eligibility after sexual assault. The 121 who presented 72 hours after assault were excluded, as were the 81 who were determined to have "no" risk for HIV acquisition. Of the subjects who were at "high" risk (71) or unknown risk (829), 798 were offered AZT/3TC plus lopinavir/ritonavir for 28 days; 347 (43%) accepted, and, of these, 111 (32%) completed the full course of treatment. Adverse events accounted for 81% of the discontinuations for which explanations were available. Most PEP recipients (96%) reported at least one adverse event of any grade; 77% reported at least one event of grade 2 to 4 severity. Notably, adverse event rates did not differ between those who completed PEP and those who did not [despite this, the author reviewing this study concluded that] Adverse events have often been thought to cause discontinuations, but this idea has limited support in the data.”

“Initial concerns about severe side effects and toxicities have been ameliorated by experience with health-care workers who have taken PEP [post-exposure prophylaxis, e.g. AIDS drugs after a needlestick injury] after occupational exposures. Of 492 health-care workers reported to the occupational PEP registry, 63% took at least three medications. Overall, 76% of workers who received PEP and had 6 weeks of follow-up reported certain symptoms (i.e., nausea [57%] and fatigue or malaise [38%]). Only 8% of these workers had laboratory abnormalities, few of which were serious and all of which resolved promptly at the end of antiretroviral treatment. Six (1.3%) reported severe adverse events, and four stopped taking PEP because of them. Of 68 workers who stopped taking PEP despite exposure to a source person known to be HIV-positive, 29 (43%) stopped because of side effects. According to the U.S. nPEP surveillance registry, among 107 exposures for which nPEP was taken, the regimen initially prescribed was stopped or modified in 22%; modifications or stops were reported because of side effects in half of these instances. In addition to reports in these registries, serious side effects have been reported (e.g., nephrolithiasis and hepatitis) in the literature. [now read the first sentence again]…Adherence to antiretroviral medications can be challenging, even for 28 days. In addition to common side effects such as nausea and fatigue, each dose reminds the patient of his or her risk for acquiring HIV infection…sexual assault survivors often decline nPEP, and many who do take it do not complete the 28-day course. This pattern has been reported in several countries and several programs in North America. In Vancouver, 71 of 258 assault survivors accepted the 5-day starter pack of nPEP, 29 returned for additional doses, and eight completed 4 weeks of therapy”

“A 59-year-old nurse of Korean origin from our HIV ward sustained a needle-stick injury with an HIV-contaminated needle. A potent PEP regimen comprising ZDV[AZT]/3TC (Combivir) 300/150 mg twice a day (bid) and LPV/r (Kaletra [Lopinavir]) 400/100 mg bid was instituted 2 hours after exposure. The following day, she experienced weakness and nausea, followed by acute deterioration of her condition. On admission, the patient was somnolent but rousable. She was unable to communicate appropriately but could open her eyes on command…Under initial therapy comprising vasopressors and fluid substitution her cardiovascular situation stabilized temporarily, before she developed acute renal [kidney] failure with anuria and hypoxaemic respiratory failure several hours after admission…The patient experienced a delayed recovery, suffering from sustained severe vertigo and weakness. Renal function also recovered after a polyuric phase of about 2 weeks’ duration. After 6 weeks of hospitalization, and a further 5 weeks in a neurological rehabilitation centre, she was finally discharged. At that time, she was still suffering from vertigo, concentration difficulties and neuropsychological cognition disorder. Other organ systems recovered completely and were unremarkable. Six months after the incident, she was still unable to resume her work. …Although the exact cause and mechanism of this incident remain unclear, the timely coincidence with PEP initiation suggests a primarily drug-induced cardiovascular failure leading to severe hypotension, shock and subsequent effects on pulmonary, renal and neurological function.”

“Non-occupational post exposure prophylaxis for HIV is not generally indicated for community needle-stick exposures.”

“In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3–4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe [but without long-term follow-up this claim is a bit shaky] even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.”

“We report the cases of a young woman who received post-exposure prophylaxis (PEP) with two protease inhibitors, prescribed sequentially, and developed a generalized allergic skin rash to both…These rashes, as well as producing patient discomfort, caused significant anxiety in the patient and the managing clinicians. They were severe enough to require several days on leave. There was concern that the rashes may represent acute HIV seroconversion illness, and an HIV proviral DNA test was ordered and was negative.”

“Although the feasibility of prophylaxis [AIDS drugs] after non-occupational exposure to HIV has been demonstrated, there are no data measuring the efficacy or effectiveness of PEP in the nonoccupational setting, although this therapy is being offered in various communities…the cost of prophylaxis after nonoccupational exposures is high, and adverse effects are relatively common and can rarely be fatal.”

“we report the case of a 32-year-old male HIV-seronegative patient who twice received antiretroviral postexposure prophylaxis after having repeated high-risk sexual contacts with an HIV-infected partner. Postexposure prophylaxis consisted of two 3-week courses of stavudine 40 mg twice a day, lamivudine 150 mg twice a day, and efavirenz 300 mg twice a day. Treatment episodes were 10 weeks apart. The patient reported no change in physical activity or diet during or after this period. The patient has remained HIV seronegative now for 4 months after the last exposure. Within 6 weeks after the second course of postexposure prophylaxis he developed a rapid increase in abdominal girth, associated with bloating and loss of appetite…The clinical picture resembles the ‘protease paunch’ first described by Miller et al. Computed tomography…showed visceral and subcutaneous fat accumulation…The abdominal fat accumulation has persisted now for 4 months after the last exposure to antiretroviral drugs.”

“[the purpose of this study was to] evaluate the impact of official recommendations for non-occupational HIV post-exposure prophylaxis (PEP), issued in France in 1998, on physicians' prescriptions and attitudes and the occurrence of severe PEP side-effects...Nationally, from 1997 to 1999, PEP requests and prescriptions increased sevenfold and ninefold, respectively. Most requests followed sexual exposure (71% in 1997 and 86% in 1999; P = 10(-6)). The proportion of prescriptions for exposure to a known HIV-infected person decreased from 78% in 1997 to 41% in 1999 (P = 10(-6)). Three-drug combination therapies increased from 46% in 1997 to 83% in 1999 (P = 10(-6)). In 1999, 13 (0.9%; 95% confidence interval, 0.5-1.5%) severe reversible adverse events occurred [were reported] among patients on a three-drug regimen. Prescription attitudes based mainly on risk assessment in 1997 (64% versus 33% in 1999) were based mainly on the request of the patient in 1999 (41% versus 11% in 1997)...Recommendations were followed by an increase of PEP, particularly after less risky exposures, and a substantial risk of severe side-effects. PEP should be restricted to well-documented exposures for which the risk of transmission outweighs the risk of severe side-effects. Drug regimens should be revised.”

“The US National Clinicians’ Post-Exposure Prophylaxis Hotline has received more than 19,000 calls. We recommend nevirapine for post-exposure prophylaxis only under extraordinary circumstances…If these criteria are met, the risks and benefits of nevirapine…should be explained to HCWs [health care workers]…The HCW should be monitored carefully for toxic effects; nevirapine should be stopped if adverse events develop or are suspected.”

“Sixty-six (26%) of the 251 patients to whom zlnPEP [Post-exposure prophylaxis with Zidovudine (AZT), Lamivudine (3TC) and Nelfinavir] was given were lost to follow-up after the first or second (day 2) consultation. For 106 (57%) of the remaining 185 patients (74%), zlnPEP was discontinued before day 28 of PEP either because the source patient tested negative for HIV or because the injury was reassessed as resulting in a low risk for transmission of HIV. In 95 of these cases (89.5%), PEP was discontinued before day 3. Adverse effects were reported before discontinuation of zlnPEP in 10 (9.5%) of these 106 persons (including 7 patients who discontinued zlnPEP before day 3). For 8 (10%) of the remaining 79 patients (43%), zlnPEP was discontinued because of adverse effects (median treatment period, 8.5 days). Twenty patients (25%) discontinued receiving nelfinavir but continued prophylaxis with zidovudine and lamivudine (median period during which the full regimen was received, 9 days). Fifty-one (65%) of these 79 patients received zlnPEP for the full 28 days of treatment, and 39 (76%) of these 51 patients experienced at least 1 adverse effect (median treatment period before onset of adverse effects, 3 days). The most frequently occurring adverse effects were diarrhea (in 31 [79%] of the individuals who reported at least 1 adverse effect) and nausea/vomiting (in 24 [62%])”

“Four individuals declined to initiate medication. [in sexual or drug injection exposures believed to be of low risk] the combination of zidovudine [AZT] plus lamivudine [3TC] was initially prescribed for 351 (86%) of the 397 individuals who elected to be treated. Didanosine and stavudine were prescribed for 31 exposures (8%). Nelfinavir was prescribed infrequently and according to the prespecified criteria for adding a third agent (3%) [higher risk situations]…The percentage of treatment completion and adherence that was observed occurred despite considerable subjective toxicity, including nausea (52%), fatigue (44%), headache (24%), diarrhea (15%), and anorexia (12%)…Other than the 37 participants who were lost to follow up, the principal reasons for discontinuing treatment were medication toxicities (27) and reevaluation of the risk for HIV exposure…(10)…The efficacy of PEP are nonoccupational exposures is not known,, but if PEP can prevent transmission, its efficacy is probably related to how quickly it can be administered. Despite our provision of 24-hour physician coverage, the average time between exposure and treatment was 33 hours.”

“FDA received reports of 22 cases of serious adverse events related to NVP [Nevirapine/Viramune] taken for PEP [post-exposure prophylaxis] from March 1997 through September 2000. These 22 events included hepatotoxicity (12), skin reaction (14), and rhabdomyolysis (one); four cases involved both hepatotoxicity and skin reaction, and one case involved both rhabdomyolysis and skin reaction.”

“A severe hypersensitivity reaction is a known complication of nevirapine and can present as a fulminant hepatitis or as a systemic syndrome with predominant cutaneous manifestations referred to as hypersensitivity syndrome (HSS) or drug rash with eosinophilia and systemic symptoms. We report a case of a severe systemic reaction with rash in a health care worker shortly after administration of a nevirapine-containing PEP [post-exposure prophylaxis] regimen...In light of the increased reports of severe hypersensitivity reactions to nevirapine, we suggest that this agent not be used for PEP until the incidence and full spectrum of nevirapine toxicity is clear, particularly if the risk of HIV seroconversion following a needlestick (0.3%) is equal to or less than the risk of this life-threatening complication.”

“While the risk of transmission of HIV via a needlestick is approximately 0.3%, the risk of serious adverse effects of these preventive strategies remains undefined. We report a case of a health care worker who experienced serious morbidity [liver failure requiring a transplant] from PEP [post-exposure prophylaxis]”

“Of the 213 patients [male and female victims of sexual assault] who were offered PEP [Post-Exposure Prophylaxis], 69 (32%) chose to initiate PEP, and 26 (12% of those initially offered PEP and 38% of those who initiated PEP) returned 1 week later to receive the additional 3 weeks of medications.”

“The regimens used for PEP [post-exposure prophylaxis] included zidovudine [AZT], lamivudine [3TC}, and indinavir in seven patients [children from 2 years old to 20], and zidovudine, lamivudine and nelfinavir in one patient. In two patients PEP was offered but never begun…Of the 8 patients who initiated PEP only two completed the prescribed 4-week regimen…The reasons…included side effects…4 of the 5 patients who received a full or partial course of PEP and could be followed reported significant side effects including four with nausea, vomiting, diarrhea, and abdominal pain and development of a rash in one individual…HIV PEP should not be used for persons with low-risk exposures such as potentially infected bodily fluids on intact skin…If a candidate for PEP is identified, initial therapy should be started as soon as possible in the emergency department after brief discussion of risk/benefit issues”]

“among health care workers who receive postexposure treatment with zidovudine[AZT], at least one third discontinue therapy because of drug intolerance. Unfortunately, data on long-term toxicity of zidovudine and on the safety of combination antiretroviral treatment in uninfected adults are not yet available.”

“In 18 cases [of occupational exposure] HIV infection occurred in spite of a complete or partial course of PEP with zidovudine [AZT]”

“24 [health care workers] who received ARV [antiretroviral] therapy [for up to 12 weeks were invited into this study of which]…16…agreed to be interviewed…Table 2. Tolerance…of triple combination therapy in 16 health-care workers: Asthenia 15 [lack of strength]; Digestive troubles (nausea, vomiting, diarrhoea, abdominal pain) 15; Headache or dizziness 7; Polyuria [excessive urination] or lumbar pain 3; Anxiety or depression 15”