HIV Prevention Knowledge Base
Biomedical Interventions: Post-exposure Prophylaxis (PEP)
Tenofovir DF Plus Lamivudine or Emtricitabine for Nonoccupational Postexposure Prophylaxis (NPEP) in a Boston Community Health Center
Completion rates for NPEP are known to be low (less than 50 percent). This may be due, in part, to adverse side effects associated with the use of ZDV either alone, or in combination with 3TC, the regimen recommended by the U.S. Public Health Service. This article describes the results of two trials conducted at the Fenway Community Health Center in Boston that examine Tenofovir DF (TDF) in combination with either 3TC or emtricitabine (FTC) for NPEP. The study looked at the side effects, adherence to treatment, and completion rates of men treated with one or the other TDF combinations (combined n = 112) and compared outcomes with 241 men who received NPEP regimens of ZDV in combination with one or two other drugs during an earlier period at the center. Results demonstrate that both TDF regimens produced milder side effects, better adherence, and high completion rates (73 percent for TDF/FTC and 88 percent for TDF/3TC) compared to ZDV regimens, where side effects were thought to have affected completion rates, which were significantly lower: 39 and 42 percent for ZDV/3TC and ZDV/3TC + third drug, respectively. Although the sample is small, the findings warrant reconsideration of recommended NPEP regimens by the U.S. Public Health Service.
Tolerability of HIV Post-Exposure Prophylaxis With Tenofovir/Emtricitabine and Lopinavir/Ritonavir Tablet Formulation
According to this study, the standard of care for post-exposure prophylaxis should be a combination of tenofovir/emtricitabine and the tablet formulation of lopinavir/ritonavir, as it is better tolerated, easier to use and has higher rates of continuation than other drug regimens. Once the participants who did not need post-exposure prophylaxis were excluded, more than four fifths continued with the treatment for 28 days. The authors suggest that completion rates could be higher if preventive measures were taken against common adverse events—diarrhea, weakness, nausea and headache, with women worse affected than men.
Prevention of Vaginal Simian Immunodeficiency Virus Transmission in Macaques by Postexposure Prophylaxis with Zidovudine, Lamivudine and Indinavir
The study shows that a triple-antiretroviral (ARV) regimen can protect macaque monkeys from vaginal exposure to the simian immunodeficiency virus (SIV), in some conditions. Three groups of six macaques (n = 18) were vaginally inoculated with SIV. A combination of three ARVs—zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV)—were administered to the experimental groups. One group received ZDV and 3TC orally and the same two drugs were administered to the second group by subcutaneous injection. Both groups received the third drug (IDV) orally; however, the subcutaneous group received a higher dose (60 mg/kg) than the oral group (20 mg/kg). Animals in the control group received placebos and all six became infected. Four of six monkeys in the subcutaneous group were afforded medium-term (230 days) protection, as compared to just one animal in the oral group. The results indicate that administering ARVs to macaques by injection versus mouth was more effective in preventing transmission of SIV; however, the reasons why some animals in both groups were protected and some were not remain unclear.
Non-occupational Postexposure Prophylaxis for HIV: A Systematic Review.
This document reports on a comprehensive review of selected studies that examine clinical effectiveness and cost-effectiveness of post-exposure prophylaxis (PEP) for HIV. The cost-effectiveness chapter identified four assessments that were selected for inclusion because they detailed all monetary costs of PEP treatment and conducted sensitivity analyses on cost-effectiveness measures for a range of different assumptions (i.e., hypothetical PEP effectiveness rates; high and low transmission probabilities). None of the studies included actual clinical effectiveness as an outcome measure. Instead, they used rates derived from occupational PEP effectiveness studies that were found to be about 80 percent effective for a single ARV regimen (not standard protocol for nonoccupational exposure). Overall, the studies showed PEP programs to be most cost-effective in cases where exposure to HIV occurs among men who have unprotected sex (of all types) with men. Cost savings were less evident for injecting drug users and women who had unprotected vaginal sex, unless there was a very high probability (greater than 73 percent) that a male partner was infected. The authors caution that it would be difficult to generalize results based on these four studies done in the United States and France to other contexts where HIV incidence and cost structure are likely to be quite different.
The Structure and Outcomes of a HIV Postexposure Prophylaxis Program in a High HIV Prevalence Setup in Western Kenya
A program that provided PEP for HIV was first set up in Western Kenya (Eldoret) at the Moi Teaching and Referral Hospital in 2001. All patients who were referred for PEP during the first five years of the program (November 2001 through December 2006) were studied retrospectively using electronic medical records. The algorithm adopted for evaluating all referrals required a test for HIV status before initiating full treatment. Of the total number who originally referred (n = 446), 19 of the 91 occupational exposures (health workers) and 55 of the 355 nonoccupational exposures (82 percent were victims of sexual assault), refused testing. The PEP regimen adopted initially (in 37 percent of the sample) was a three-drug combination (stavudine/3TC/nevirapine) that may have contributed to a hepatitis-induced patient fatality. Risk of toxicity and hepatitis is known to be associated with nevirapine. In subsequent patients treated (63 percent), the regimen used was ZDV/3TC/lopinavir-ritonavir. No differences in reported side effects or treatment completion rates were found between the two regimens. However, the completion rate for the nonoccupational cohort was less than half that (35 percent) of health workers (76 percent). The authors suggest that efforts to strengthen adherence and completion of PEP programs are necessary to improve outcomes.
Determinants of High-risk Sexual Behavior during Post-Exposure Prophylaxis to Prevent HIV Infection
The Centers for Disease Control and Prevention (CDC) guidelines recommend providing behavioral counseling to decrease sexual risk behavior in conjunction with PEP. This study examined the sexual risk behaviors of 89 men who have sex with men (MSM) and receive PEP in Boston, Massachusetts, and specifically asked about their high-risk sexual behavior in the six months prior to PEP and during the 28-day PEP period. Nineteen men (21 percent) reported unprotected anal intercourse (UAI) during PEP; and ten of these men reported UAI with partners of positive or unknown HIV status (11 percent of the overall population). In multivariate analysis, those men with higher depression scores and histories of engagement with HIV service organizations (e.g., receiving services from an HIV-related agency, donating money to HIV-related causes, etc.) were more likely to report UAI with high-risk partners. The investigators postulated that patients engaged with HIV service organizations may be more likely to believe they are protected from HIV by PEP, and thus more willing to engage in risky sexual behavior. These results highlight the need for integration of behavioral counseling for MSM receiving PEP.
Antiretroviral Drug Exposure in the Female Genital Tract: Implications for Oral Pre- and Post-exposure Prophylaxis
PEP for women is most likely to be effective when it is initiated early with a drug that quickly and effectively concentrates in the genital tract. This study examined the pharmacokinetics of oral ARV drugs in female genital secretions. Blood and cervicovaginal fluid samples were taken from 27 women on the day they started PEP, three weeks later, and then monthly for six months. All of the 11 ARV drugs examined in this study achieved detectable concentrations in genital secretions within four hours after the first dose. Of the nucleoside analogs, ZDV, TDF, 3TC, and FTC achieved higher steady-state levels in the genital tract than in the blood. The protease inhibitors studied, lopinavir and atazanavir, achieved only moderate to low concentrations in the genital secretions compared to levels in the blood; as did efavirenz, the only non-nucleoside agent studied. These findings support the use of 3TC, ZDV, TDF and FTC, nucleoside, and nucleotide reverse transcriptase inhibitors for PEP.
Assessment of Adverse Events Associated with Antiretroviral Regimens for Post-exposure Prophylaxis for Occupational and Nonoccupational Exposures to Prevent Transmission of Human Immunodeficiency Virus
The goal of this study was to assess adverse events associated with different antiretroviral therapy (ART) regimens for PEP with a particular focus on TDF-containing regimens. The investigators performed a retrospective chart review of 113 health care workers who received occupational PEP between 1999 and 2004, and 87 patients who received NPEP between 2002 and 2004. Nausea was reported by the majority of patients and health care workers who received ZDV-3TC-TDF (66 percent) or ZDV-3TC-IDV (54 percent), but less than half of those who received ZDV-3TC (29 percent) or ZDV-3TC-nelfinavir (NFV; 40 percent). Subjects who received ZDV-3TC-TDF were less likely to complete PEP than subjects who received treatment with ZDV-3TC-IDV or ZD-3TC. This study underscored the impact of adverse side effects on the completion of PEP in both occupational and nonoccupational settings.
The Public Health Impact of Widespread Availability of Non-Occupational Post-Exposure Prophylaxis Against HIV
The use of PEP is accepted and practiced widely in Australia, particularly among MSM. Only registered providers can prescribe ART, which allowed the authors of this study to identify and prospectively follow the cohort who received PEP from 1998 to 2004. Most of the 1,552 patients were male (95 percent), and the majority of sexual exposures were male-to-male (87 percent). PEP was initiated in 92 percent of patients within 72 hours. Of the 1,146 patients who returned for evaluation four weeks after starting PEP, 86 percent had completed the original or a modified regimen. Three subjects seroconverted within six months after PEP, all of whom had ongoing sexual risk behaviors in the time during and after PEP. Based on epidemiologic data, the investigators estimated that only between one and nine HIV infections were averted in the study population. This relatively small effect is attributed to the low likelihood of transmission in any one sexual encounter and the fact that many, or most, of the exposure sources were not actually infected with HIV.
Seroconversion Following Non-Occupational Post-Exposure Prophylaxis against HIV
In San Francisco, a feasibility study of PEP was conducted in which subjects were offered the drug treatment (either ZVD-3TC, stavudine-3TC, or stavudine-didanosine) and counseling sessions. Participants were part of a 52-week assessment on medication initiation, adherence, side effects, and seroconversion. Those who knew that their HIV-infected source partner had a detectable viral load on ART were also given NFV. Most of the subjects were male (95 percent), and the majority had had sexual exposure to HIV (96 percent). Seven seroconversions occurred in 702 subjects (1 percent) and these individuals started PEP significantly later than subjects who did not seroconvert (median 45.5 hours versus 32.5 hours). Three of the seroconverters started PEP more than 45 hours after exposure; and three reported missing several doses of medication. This study demonstrated that PEP is not 100 percent effective. To increase its chances of effectiveness, it must be started as quickly as possible and the importance of complete adherence must be emphasized to patients.
Introduction of HIV Post-exposure Prophylaxis for Sexually Abused Children in Malawi
This program was designed to improve the care of victims of child sexual abuse (CSA) in Malawi by routinely assessing eligibility for PEP, and to investigate the feasibility, safety, and efficacy of such treatment in a pediatric emergency department. Sixty-four children seen at Queen Elizabeth Central Hospital and Blantyre between January 2004 and December 2004 were assessed for eligibility for HIV PEP and followed prospectively for six months. Among these 64, all of whom presented a history of alleged CSA in the 12-month period, 17 were offered PEP. The remainder were not offered PEP due to the absence of physical signs of abuse (sample size, n = 20), delay in presentation beyond 72 hours from assault (n = 11), repeated sexual abuse in the preceding six months (n = 15), and HIV infection found on initial testing (n = 1). No family refused an HIV test, and no ART-related side effects were reported. Of the 17 children who commenced PEP, 1 returned for a follow-up at one month, 7 returned at three months, and 2 of 15 returned at six months post-assault. None of those who returned for a follow-up seroconverted. The authors concluded that in a resource-poor setting with a high HIV prevalence, PEP following CSA is acceptable, safe, and feasible. The authors recommended that HIV PEP be incorporated into national guidelines in countries with a high community prevalence of HIV infection.
Efficacy of Postexposure Prophylaxis after Intravaginal Exposure of Pig-Tailed Macaques to a Human-Derived Retrovirus (Human Immunodeficiency Virus Type 2)
This study investigates the critical window for initiating PEP using an animal model (macaque monkeys). The methodology was a departure from other animal studies in that vaginal exposure with a human HIV retrovirus (HIV 2), as opposed to SIV, was used. A control group (n = 4) was compared with three experimental groups (n = 4 each) that varied by treatment initiation times (12, 24, and 72 hours). The treatment regimens for the experimental groups were identical and employed a single ARV [(R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA)] for 28 days. Three animals in the control group seroconverted (one, inexplicably, did not convert). All eight animals in the 12- and 24-hour treatment initiation groups were protected. The 72-hour group had mixed results: one animal converted, one died of a cause unrelated to treatment, and two remained healthy. The researchers suggest that initiating therapy sooner than the 72-hour window generally used as a cutoff in national guidelines is likely to improve the effectiveness of treatment. The authors consider the study results to represent “proof of concept” for PEP in humans.
Prevention of SIV Infection in Macaques by (R)-9-(2-phosphonylmeth-oxypropyl)adenine
There is an urgent need for identifying effective and well tolerated ARVs that can be used to prevent HIV infection post exposure. Drugs currently being used therapeutically, such as ZDV, often produce adverse side effects. A study that used an animal model (long tail macaques) to examine the efficacy and toxicity of a new drug showed that PMPA, a reverse transcriptase inhibitor, prevented SIV in 100 percent of the exposed animals (n = 15), regardless of whether they received pre- (48 hours prior to inoculation with SIV) or post-exposure treatment (4 hours and 24 hours after inoculation). In contrast, all animals in the control group developed SIV within a one- to three-week period. The dose given to animals in the pre-exposure group was lower (20 mg/day) than those treated post-exposure (30 mg/day). None of the animals in the treatment group were observed to have had adverse effects. The results suggest that PMPA is a promising candidate for use in PEP regimens, although the efficacy of the drug in combination with others that are used in treating humans must be conducted.