Self-reported risky sexual practices among adolescents and young adults in Botswana.

BACKGROUND: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. OBJECTIVES: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities. METHODS: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. RESULTS: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44-1.80), intergenerational sex (PR 9.00; 95% CI 5.84-13.88) and transactional sex (PR 3.46; 95% CI 2.07-5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41-0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45-0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57-0.74). CONCLUSIONS: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming.

Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls.

OBJECTIVES: To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. DESIGN: Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. METHODS: We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. RESULTS: There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. CONCLUSION: Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

Surgical complications in 275 HIV-infected liver and/or kidney transplantation recipients.

BACKGROUND: In this report, we examine the surgical safety and complications (SC) among 125 liver (L) and 150 kidney (K) HIV+ transplantation (TX) recipients in a prospective nonrandomized U.S. multicenter trial. METHODS: Subjects were required to have CD4+ T-cell counts >200/100 cells/mm3 (K/L) and undetectable plasma HIV-1 RNA (Viral Load [VL]) (K) or expected posttransplantation suppression (L). Impact of SCs (N ≥ 7) was evaluated by use of the proportional hazards models. Baseline morbidity predictors for SCs (N ≥ 7) were assessed in univariate proportional hazards models. RESULTS: At median 2.7 (interquartile range 1.9-4.1) and 2.3 (1.0-3.7) years after TX, 3-month and 1-year graft survival were [K] 96% (95% CI 91%-98%) and 91% (95% CI 85%-94%) and [L] 91% (95% CI 85%-95%) and 77% (95% CI 69%-84%), respectively. A total of 14 K and 28 L graft losses occurred in the first year; 6 K and 11 L were in the first 3 months. A total of 26 (17%) K and 43 (34%) L experienced 29 and 62 SCs, respectively. In the liver multivariate model, re-exploration was marginally associated (hazard ratio [HR] 2.8; 95% CI 1.0-8.4; P = .06) with increased risk of graft loss, whereas a greater MELD score before transplantation (HR 1.07 per point increase; 95% CI: 1.01-1.14; P = .02), and detectable viral load before TX (HR 3.6; 95% CI 0.9-14.6; P = .07) was associated with an increased risk of wound infections/dehiscence. CONCLUSION: The rates and outcomes of surgical complications are similar to what has been observed in the non-HIV setting in carefully selected HIV-infected liver and kidney TX recipients.

Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection.

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

Preventing human immunodeficiency virus infection among sexual assault survivors in Cape Town, South Africa: an observational study.

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.

A randomized noninferiority trial of standard versus enhanced risk reduction and adherence counseling for individuals receiving post-exposure prophylaxis following sexual exposures to HIV.

BACKGROUND: The National HIV/AIDS Strategy proposes to scale-up post-exposure prophylaxis (PEP). Intensive risk reduction and adherence counseling appear to be effective but are resource intensive. Identifying simpler interventions that maximize the HIV prevention potential of PEP is critical. METHODS: A randomized noninferiority study comparing 2 (standard) or 5 (enhanced) risk reduction counseling sessions was performed. Adherence counseling was provided in the enhanced arm. We measured changes in unprotected sexual intercourse acts at 12 months, compared with baseline; HIV acquisition; and PEP adherence. Outcomes were stratified by degree of baseline risk. RESULTS: We enrolled 457 individuals reporting unprotected intercourse within 72 h with an HIV-infected or at-risk partner. Participants were 96% male and 71% white. There were 1.8 and 2.3 fewer unprotected sex acts in the standard and enhanced groups. The maximum potential risk difference, reflected by the upper bound of the 95% confidence interval, was 3.9 acts. The difference in the riskier subset may have been as many as 19.6 acts. The incidence of HIV seroconversion was 2.9% and 2.6% among persons randomized to standard and enhanced counseling, respectively, with a maximum potential difference of 3.4%. The absolute and maximal HIV seroconversion incidence was 9.9% and 20.4% greater in the riskier group randomized to standard, compared with enhanced, counseling. Adherence outcomes were similar, with noninferiority in the lower risk group and concerning differences among the higher-risk group. CONCLUSIONS: Risk assessment is critical at PEP initiation. Standard counseling is only noninferior for individuals with lower baseline risk; thus, enhanced counseling should be targeted to individuals at higher risk.

Outcomes of kidney transplantation in HIV-infected recipients.

BACKGROUND: The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. METHODS: We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. RESULTS: Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications. CONCLUSIONS: In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Evolving clinical strategies for transplantation in the HIV-positive recipient.

The transplant community has been slow to recognize the efficacy of highly active antiretroviral therapy in changing the course of human immunodeficiency virus (HIV) infection to a chronic condition. People infected with HIV are dying less often from progression of HIV to acquired immune deficiency syndrome. Unfortunately, there is an increasing rate of morbidity and mortality from comorbidities resulting in end-stage liver and kidney disease, prompting some transplant centers to eliminate HIV infection as a contraindication to transplantation. This overview will describe the evolving clinical strategies that have resulted in good outcomes after solid organ transplantation in the HIV-positive recipient.

Postexposure prophylaxis after sexual exposure to HIV.

PURPOSE OF REVIEW: HIV postexposure prophylaxis is often recommended following potential sexual exposure to HIV. Recent data address the effectiveness of postexposure prophylaxis and prevention counseling, cost-effectiveness, antiretroviral options, challenges with nonoccupational postexposure prophylaxis among adolescents and children and following sexual assault in high HIV prevalence areas, and a successful program in Amsterdam. RECENT FINDINGS: Postexposure prophylaxis is not completely protective. Seroconversion may result from antiretroviral failure or from ongoing exposures. Postexposure prophylaxis associated risk reduction counseling results in reductions in subsequent risk behavior. Programs that target outreach and limit prescriptions to those with exposure sources who are at risk of being HIV infected are cost-effective. Less restrictive guidelines result in more prescriptions for low-risk exposures; this practice is not cost-effective. The ideal antiretrovirals for postexposure prophylaxis use have not been established. Tenofovir has several attractive properties. Developing systems to support the effective delivery of postexposure prophylaxis among children and adolescents and following sexual assault in high HIV prevalence, resource limited settings is challenging. SUMMARY: Numerous national and international guidelines recommend postexposure prophylaxis following potential sexual exposure to HIV. Maximizing adherence and minimizing subsequent HIV exposures will be critical to enhancing the effectiveness of this HIV prevention intervention.

Solid organ transplantation is a reality for patients with HIV infection.

Recent policies, guidelines, and laws reflect promising preliminary outcomes among transplant recipients with HIV infection, and ethical analyses suggest that it is not justifiable to deny solid organ transplantation based solely on HIV-infection status. These studies consistently describe stable HIV disease following liver and kidney transplantation. Despite good graft survival, kidney allograft rejection occurs frequently, and serious non-AIDS-defining infections requiring hospitalization are common following antirejection therapy. Profound interactions between immunosuppressants and antiretroviral drugs require careful monitoring, dose adjustment, and highly effective communication between the patient and a multidisciplinary group of health care providers. Despite these scientific and policy advances, many health care providers and patients remain unaware of ongoing progress in this field. The implications are critical, as late referral for liver transplant evaluation increases the pretransplant mortality risk. Because important patient selection and clinical management questions remain, it is critical that ongoing studies are completed quickly.

Liver transplantation in HIV-infected recipients.

Although human immunodeficiency virus (HIV)-infected patients are living longer and dying less often from complications related to acquired immunodeficiency syndrome (AIDS), they are experiencing significant morbidity and mortality related to end-stage liver disease. Advances in the management of HIV disease have made it difficult to continue denying transplantation to this population based upon futility arguments alone. Patient and graft survival rates in HIV-infected study subjects appear similar to those in large transplant databases. There are no reports suggesting significant HIV disease progression. There are substantial interactions between immunosuppressants and antiretroviral drugs that require careful monitoring and dose adjustment. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team and the primary HIV care provider. It is critical that HIV clinicians and hepatologists are aware that liver transplantation is an option for HIV-infected patients at many transplant centers as delays in referral result in unnecessary mortality during the pretransplantation evaluation process.

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation.

The outcome of patients with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) referred for liver transplantation (LT) is unknown. A high frequency of lamivudine-resistant (LAM-R) HBV infection may increase the risk of liver-related death pre-transplantation and prophylaxis failure post-transplantation. We evaluated the association of LAM-R HBV on pre-transplant survival and post-transplant outcomes in 35 consecutive HIV-HBV coinfected patients referred for LT between July 2000 and September 2002. At the time of referral, the median CD4 count was 273/mm, MELD was 14, and LAM-R HBV infection was present in 67%. Among these referred patients, 26% were listed, 29% not listed due to relative/absolute contraindications; 26% not listed as too early for LT; 9% not listed as too sick for LT; and 11% died during transplant evaluation. Of the 9 listed patients, 4 remained listed, 1 died 18 months post-referral, and 4 were transplanted (11% of total) 3 to 40 months after listing. Of 17 evaluated but not listed patients, 5 died (p=0.38 compared to listed group) and all deaths were liver-related. All the HBV-HIV coinfected patients, who were transplanted, are HBsAg negative and have undetectable HBV DNA levels on prophylactic therapy using hepatitis B immune globulin (HBIG) plus lamivudine, with and without tenofovir or adefovir, with median 33.1 months follow-up. Late referral and the presence of LAM-R HBV pre-transplantation are common in referred HIV-HBV patients. In HIV-HBV coinfected patients undergoing LT, HBV recurrence is successfully prevented with combination prophylaxis using HBIG and antivirals.

Solid organ transplantation: referral, management, and outcomes in HIV-infected patients.

Advances in HIV management make it difficult to deny solid organ transplantation to HIV-infected patients based on futility arguments. Preliminary studies suggest that both patient and graft survival are similar in HIV-negative and HIV-positive transplant recipients. While there has been no significant HIV disease progression, substantial interactions between immunosuppressants and antiretroviral drugs necessitate careful monitoring. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team, the primary HIV care provider, and the patient. Timely referral for transplant evaluation will prevent unnecessary mortality during the pre-transplant evaluation process.

Seroconversion following nonoccupational postexposure prophylaxis against HIV.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients.

BACKGROUND: With advances in antiretroviral therapy, many human immunodeficiency virus (HIV)-infected individuals are living longer and developing end-stage renal or hepatic disease requiring transplantation. Maintaining the viability of the transplant and suppressing HIV replication requires concomitant use of immunosuppressants (e.g., cyclosporine) and antiretrovirals (e.g., protease inhibitors or nonnucleoside reverse transcriptase inhibitors), which leads to drug interactions. To assist in appropriate clinical management of HIV-infected transplant recipients, the authors describe the pharmacokinetic interactions between cyclosporine and the antiretroviral medications, and required modifications of cyclosporine dosing. METHODS: Eighteen HIV-infected subjects with end-stage kidney or liver disease underwent transplantation. Subjects had pharmacokinetic studies before transplantation and for up to 2 years posttransplantation (at weeks 2-4, 12, 28, 52, and 104). Protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and cyclosporine concentrations were measured by liquid chromatography-mass spectrometry in plasma and whole blood, respectively. RESULTS: Subjects using protease inhibitors and cyclosporine had a threefold increase in cyclosporine area under the curve (4,190+/-2,180-11,900+/-1,600 ng*hr/mL, P<0.01), necessitating an 85% reduction in cyclosporine dose over a 2-year period (1.3+/-1.5-0.2+/-0.0 mg/kg/dose), leading to a progressive increase in oral cyclosporine bioavailability (R=0.92, P<0.02). Subjects on nonnucleoside reverse-transcriptase inhibitors showed minimal interactions with cyclosporine, and subjects on both HIV treatments had intermediate responses. CONCLUSIONS: HIV-infected transplant recipients on protease inhibitors require markedly lower doses of cyclosporine, with continued lowering of the cyclosporine dose over time and ongoing cyclosporine trough monitoring because of progressively increasing cyclosporine bioavailability. Medication changes must be carefully managed to avoid insufficient immunosuppression or toxicity resulting from drug interactions.

Comprehensive guidelines translate research findings into clinical policy for HIV-infected transplant candidates and recipients

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