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.     

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda

BACKGROUND: The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. OBJECTIVE: To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. DESIGN AND METHODS: A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants' HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. RESULTS: Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2-0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. CONCLUSIONS: Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.     

Fertility desires and preferences for safer conception strategies among people receiving care for HIV at a publicly-funded clinic in Seattle,WA

Understanding fertility desires and preferences for HIV prevention among individuals living with HIV, including the potential use of pre-exposure prophylaxis (PrEP) by HIV uninfected partners, can inform the delivery of safer conception counseling to reduce the risk of HIV transmission during pregnancy attempts. Men and women, predominantly heterosexual, engaged in HIV care in Seattle, WA, self-administered a questionnaire and we abstracted antiretroviral therapy (ART) status and HIV viral levels from medical records. We summarized participants’ sexual behavior, fertility desires, and preferences for safer conception strategies and used log-binomial regression to identify demographic, sexual, and behavioral factors associated with perceived acceptability of PrEP for HIV uninfected partners during pregnancy attempts. 52% of the 150 participants were female and the mean age was 48 years (range 23–74). 94.7% of participants were using ART and 79.3% had HIV viral load < 40 copies/mL. 22.2% of men and 34.6% of women reported that a healthcare provider had initiated discussion about fertility desires. 28.7% of participants were reproductive-age and desired children. Among sexually active reproductive-age participants with fertility desires, 56.3% reported inconsistent condom use and 62.5% did not report using effective birth control. 74.4% of reproductive age participants with fertility desires perceived that PrEP would be acceptable to an HIV uninfected partner and there were no significant predictors of PrEP acceptability. Nearly one third of reproductive-aged individuals living with HIV expressed fertility desires, highlighting a need for safer conception counseling in this setting. PrEP and ART were favored safer conception strategies.     

Engagement in HIV care and sexual transmission risk behavior among men who have sex with men using online social/sexual networking in Latin America

HIV/AIDS in Latin America is concentrated among men who have sex with men (MSM). However, accurate estimates of engagement in HIV care in this population can be difficult to ascertain because many do not self-identify as MSM. Given evidence of decreased HIV transmissibility in the context of antiretroviral therapy (ART) adherence, identifying individuals not in care who are engaging in HIV transmission risk behavior is crucial for secondary prevention. Primary aims of this study were to examine engagement in care from testing to ART adherence among MSM using online social/sexual networking across Latin America, and whether individuals not in care at each step reported greater sexual transmission risk behavior than those in care. In the overall sample (n = 28,779), approximately 75% reported ever being tested for HIV, and 9% reported having received an HIV diagnosis. Among known HIV-infected individuals, 20% reported not being in care, 30% reported not taking ART, and 55% reported less than 100% ART adherence. Over one-third of HIV-infected individuals reported sexual HIV transmission risk behavior, defined as unprotected anal intercourse (UAI) with a male partner of different/unknown HIV serostatus in the past three months. HIV-infected individuals not engaged in care more often reported UAI compared to those in care (OR = 1.29; 95% CI = 1.01–1.66). Although not statistically significant, HIV-infected individuals not on ART more often reported UAI compared to those on ART (OR = 1.18; 95% CI = 0.94–1.47). Individuals who reported less than 100% ART adherence more often reported UAI compared to individuals with 100% adherence (OR = 1.55; 95% CI = 1.26–1.90). Findings demonstrate that a substantial portion of HIV-infected MSM in Latin America who are likely not virologically suppressed from lack of ART use or adherence report sexual HIV transmission risk. Tailoring secondary HIV prevention for MSM in Latin America who are not in HIV care or adherent to ART may be warranted.     

Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation

OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose (FDG). Various patterns of FDG accumulation in HIV-positive subjects have been described previously and hypothesized to potentially represent regions of active HIV replication and or nodal activation. We evaluated the utility of FDG scanning as a tool to study HIV pathogenesis. DESIGN: We evaluated FDG biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected subjects to determine the impact on pattern of nodal activation of: HIV infection; stage of HIV infection and degree of viremia; and HAART. In addition, we attempted to image anatomical site(s) of on-going HIV replication in subjects with suppressed HIV viremia on ART, but who subsequently discontinued ART. METHOD: We performed FDG imaging on five groups: HIV-negative, HIV-positive with early infection, HIV-positive with advanced disease, HIV-positive with suppressed viral loads, and HIV-positive who stopped ART. RESULTS: Healthy HIV subjects with suppressed viral loads and HIV-negative individuals had no or little FDG nodal accumulation or any other hypermetabolic areas, whereas viremic subjects with early and advanced HIV had increased FDG in peripheral nodes, indicating that FDG potentially identifies areas of HIV replication. FDG biodistribution was similar between early and advanced-stage. Four of five subjects taken off ART had negative baseline scans but developed nodal uptake and increases in viral load. CONCLUSIONS: Abnormal FDG accumulation occurs in nodes of subjects with detectable viral loads. Interruption of effective ART results in activation of previously quiescent nodal areas.     

High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis

OBJECTIVES: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.     

Factors associated with unprotected sexual intercourse with steady male, casual male, and female partners among men who have sex with men in Barcelona, Spain.

To increase understanding of the HIV epidemic among MSM in Barcelona, anonymous questionnaires were completed by 640 MSM recruited in the city in 2002. The prevalence of unprotected anal intercourse (UAI) with casual male partners in the prior 12 months was higher among self-reported HIV-positive men (confirmed through saliva testing) than among men who were HIV-negative or of unknown serostatus (35% vs. 20%, p < .01). The prevalence of UAI with steady male partners was substantially lower among HIV-positive men than other men (28% vs. 60%, p < .01). In multivariate analyses, UAI with casual partners was more likely among HIV-positive individuals; those who used drugs before sex; perceived less acceptance of their sexual orientation by family, friends, or coworkers; and were less concerned about HIV prevention because of antiretroviral therapy (ART). UAI with steady partners was more likely among HIV-negative men with seroconcordant partners, those living with a partner, and men less concerned about HIV prevention because of ART. Findings indicate a need for prevention programs targeting HIV-positive MSM in Barcelona. Attention to substance use and attitudes about HIV prevention are needed for MSM in general.     

Breastmilk erythropoietin and mother-to-child HIV transmission through breastmilk

A third to a half the 1.5 million HIV-positive children in the world today acquired their infection via breastfeeding. However, what protects the 85% of breastfed babies of HIV-infected mothers who do not become infected? We postulate that erythropoietin (EPO), a hormone in human milk, has a role in the prevention of HIV transmission during breastfeeding. EPO might maintain mammary epithelium integrity, thereby reducing viral loads in milk, or maintain intestinal epithelial integrity in the breastfed neonate, and thus preventing ingested milk-borne virus being infective. This hypothesis could be tested by administration of recombinant human EPO parenterally to HIV-infected mothers or enterally to breastfed babies, or both, and assessment of the effect on mammary permeability, viral load in milk, and intestinal permeability in babies. If our hypothesis is correct, EPO treatment for mother or baby, or both might help prevent transmission of HIV.     

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.     

抗病毒治疗对于艾滋病疫情影响的研究

抗病毒治疗（ART）可降低艾滋病病毒（HIV）感染者／艾滋病（AIDS）病人（HIV／AIDS病人）的病毒载量,从而对AIDS的流行和发展产生影响。文章针对国内外ART对AIDS疫情影响的相关研究进行综述。从传染源的影响来看,ART能抑制HIV／AIDs病人血液、生殖道、直肠壁的病毒复制,但仍存在感染的风险。从传播途径的影响来看,ART是否会增加危险性行为尚存争议。从高危人群的影响来看,ART应用于高危人群的预防具有一定的效果,但还存在药物不良反应、耐药性等诸多负面效应。因而亟须更多研究对ART所带来的AIDS疫情趋势影响进行预测、评估和验证。     

Low uptake of HIV testing and no HIV positivity in stable serodiscordant heterosexual partners of long-term treated HIV-infected Thais

The objective of this study was to characterize HIV-serodiscordant heterosexual couples and to evaluate acceptance for HIV testing and HIV prevalence in nonindex partners. We conducted a cross-sectional study with quantitative and qualitative components. Two cohorts of 1767 HIV-positive people were screened to identify heterosexual HIV-serodiscordant couples. HIV-positive partners (index) were administered a questionnaire; CD4, viral load (VL), and antiretroviral therapy (ART) history were gathered from clinical records. HIV-negative/unknown status partners (nonindex) were invited for a similar questionnaire and HIV testing. In-depth interviews with three HIV-serodiscordant couples were conducted. Two hundred and ninety-seven index partners agreed to enroll in this study. The median duration of the relationship was 10 years, and 81% were sexually active. All but two index partners were on ART, and 98% had VL < 1000 copies/mL. Only 111 (37%) nonindex partners came for HIV testing, and all of them tested HIV-negative. In addition, only 41% of nonindex partners had HIV testing in the last one year. The main reasons for the nonindex partners not to come for HIV testing were “no interest” (n = 117, 63%) and “nondisclosure of HIV status” (n = 46, 25%). The latter was substantiated and explained by the qualitative outcome of this study, suggesting relation to stigma against HIV-positive people. Our results support the WHO recommendation for starting ART for treatment and prevention in HIV-serodiscordant couples at any CD4 count. Furthermore, we recommend the dissemination of data showing that no HIV transmission in heterosexual couples through sex practice has been observed provided VL is suppressed. This could be a powerful tool for effective fight against stigma and self-stigma in people living with HIV.     

Effects of HIV-related stigma among an early sample of patients receiving antiretroviral therapy in Botswana

Botswana, with its estimated HIV prevalence of 37%, instituted a policy of universal access to antiretroviral therapy (ART) in 2002. Initial enrolment lagged behind expectations, with a shortfall in voluntary testing that observers have attributed to HIV-related stigma - although there are no published data on stigma among HIV-positive individuals in Botswana. We interviewed 112 patients receiving ART in 2000, finding evidence of pervasive stigma in patterns of disclosure, social sequelae, and delays in HIV testing. Ninety-four percent of patients reported keeping their HIV status secret from their community, while 69% withheld this information even from their family. Twenty-seven percent of patients said that they feared loss of employment as a result of their HIV status. Forty percent of patients reported that they delayed getting tested for HIV; of these, 51% cited fear of a positive test result as the primary reason for delay in seeking treatment, which was often due to HIV-related stigma. These findings suggest that success of large-scale national ART programmes will require initiatives targeting stigma and its social, economic and political correlates.     

Antiviral agents and HIV prevention: controversies, conflicts, and consensus

Antiviral agents can be used to prevent HIV transmission before exposure as preexposure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups - including intravenous drug users and MSM - has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation.     

How Might We Cure HIV?

Antiretroviral therapy (ART) does not eliminate HIV-1 from latently infected reservoirs, and this remains the critical obstacle to the eradication of infection. Although ART is effective in suppressing viral load, life-long ART is burdensome in many respects. Given expanding numbers of HIV-infected individuals on ART worldwide, there is an urgent need to examine the possibility that innovative therapies might eradicate infection, and obviate the need for life-long medical therapy for HIV-positive people around the world. Several approaches to eradicating the latent HIV reservoir and curing infection have been proposed and are under study. An initial strategy seeks to induce the expression of the latent integrated proviral genomes within resting CD4+ T cells, so that viral proteins or particles may be revealed and allow these cellular reservoirs to be cleared. The inducing agents that have been studied recently are inhibitors of histone deacetylase (HDAC) such as suberoylanilide hydroxamic acid (SAHA). Such induction of viral expression seems unlikely in itself to efficiently clear all latently infected cells. Therefore, it seems likely that parallel efforts to augment the HIV-specific immune response with specific immunotherapies or vaccination may be required. Recently, efforts to achieve immune augmentation by ex vivo expansion of viral specific cytotoxic T-cell lymphocytes derived from HIV-infected patients have yielded an augmented HIV-specific immune response in vivo, as have cellular vaccinations delivered by administration of dendritic cells. As HIV latency and the persistence of infection despite effective ART is multifactorial, the eradication of HIV infection may require multiple approaches.     

Identifying,linking, and treating people who inject drugs and were recently infected with HIV in the context of a network-based intervention

ABSTRACT

Identifying and linking people to care soon after HIV infection could limit viral transmission and protect their health. This work aims at describing the continuum of care among recently HIV-infected people who inject drugs (PWID) and participated in an intervention in the context of an HIV outbreak in Athens, Greece. The Transmission Reduction Intervention Project (TRIP) conducted risk network-based contact tracing and screened people for recent HIV infection. A comprehensive approach with a case management component that aimed to remove barriers to accessing care was adopted. Follow-up data on antiretroviral treatment (ART) and HIV-RNA levels were obtained from HIV clinics. TRIP enrolled 45 recently HIV-infected PWID (80% male) with a median viral load at recruitment of 5.43 log₁₀ copies/mL. Of the recently infected persons in TRIP, 87% were linked to care; of these, 77% started ART; and of those on ART, 89% achieved viral load <200 copies/mL. TRIP and its public health allies managed to get most of the recently HIV-infected PWID who were identified by the program into care and many of them onto ART. This resulted in very low HIV-RNA levels. Treatment as prevention can work if individuals are aided in overcoming difficulties in entry to, or attrition from care.

Trial registration: Uniform Trial Number identifier: NCT01827228.     

U.S. Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women

These recommendations were developed by the U.S. Public Health Service to address the increasing epidemic of human immunodeficiency virus (HIV) infection among women and their infants. The recommendations stress the importance of early diagnosis of HIV infection for the health of both women and their infants and are based on advances made in HIV-related treatment and prevention. The most significant advance for this population has been the results from a placebo-controlled, clinical trial that indicated that administration of zidovudine to HIV-infected pregnant women and their newborns reduced the risk for perinatal transmission of HIV by approximately two-thirds. This document recommends routine HIV counseling and voluntary testing for all pregnant women and is intended to serve as guidance for health-care providers in educating women about the importance of knowing their HIV infection status. For uninfected women, such HIV counseling and testing programs can provide information that can reduce their risk for acquiring HIV; for women who have HIV infection, these programs can enable them to receive appropriate and timely medical interventions for their own health and for reducing the risk for perinatal (i.e., mother to infant) and other modes of HIV transmission. These programs also can facilitate appropriate follow-up care and services for HIV-infected women, their infants, and other family members.     

Hepatitis B testing and vaccination in patients recently diagnosed with HIV infection

The British HIV Association currently recommends vaccination against hepatitis B virus (HBV) for all susceptible HIV-infected individuals, therefore a retrospective analysis was performed on case notes from all patients diagnosed with HIV infection in our department for a one-year period from 1st August 2005; in each case HBV serological testing and vaccination status were recorded. Fifty-one patients were diagnosed with HIV infection during the study period, however, serological testing for HBV infection had been undertaken in only 76% of susceptible patients by 12 months following their HIV diagnosis. At the time of analysis only 31% of patients were adequately vaccinated against HBV, with recorded HBV surface antibody titres of >100 IU/L. HBV remains a considerable cause of morbidity and mortality in HIV-infected individuals and this study suggests that prevention or detection of HBV infection requires increased vigilance on the part of physicians managing HIV-positive patients.