Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs.
Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (p = 0.0511 and p = 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (p = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for 1 woman, while statistical methods were consistent with PBMC compartmentalization for 6 women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence.
doi:10.1002/jmv.22269
PMCID: PMC3243959
PMID: 22170544
NS5B; HVR1; diversity; quasispecies; extrahepatic replication
Saravanan, Shanmugam | Madhavan, Vidya | Solomon, Sunil S. | Kantor, Rami | Katzenstein, David | Sivamalar, Sathasivam | Kumarasamy, Nagalingeswaran | Smith, Davey M. | Mayer, Kenneth H. | Solomon, Suniti | Balakrishnan, Pachamuthu
Summary
In HIV-1 subtype C infected populations in south India, we searched for novel mutations associated with failing antiretroviral therapy that included nucleoside reverse transcriptase (RT) inhibitors. HIV-1 RT sequences were generated from treated and untreated groups and each nucleotide position was analysed with appropriate corrections for multiple testing. We found that nonsynonymous mutations at positions 208 and 228 were strongly associated with the presence of thymidine analogue mutations in the treated group, and were not present at all in the naïve group. The role of these substitutions on treatment outcomes and the evolution of drug resistance in HIV-1 subtype-C infected populations warrant further investigation.
doi:10.1097/QAI.0b013e31823e2d2b
PMCID: PMC3259528
PMID: 22245718
HIV-1 Drug Resistance Mutation; HIV-1 Subtype C; HIV in India; Thymidine Analogue Mutation (TAMs); HIV-1 RT mutation at codon 208; 228; HIV Drug Resistance in India
American men who have sex with men (MSM) continue to have increased rates of HIV and STD. Between 2004 and 2010, 1155 MSM were screened for HIV and/or STD at a Providence, RI, bathhouse. The prevalence of HIV was 2.3%; syphilis, 2.0%; urethral gonorrhea, 0.1%; urethral Chlamydia, 1.3%; 2.2% of the men had hepatitis C antibodies. Although 43.2% of the men engaged in unprotected anal intercourse in the prior two months, the majority of the men thought that their behaviors did not put them at increased risk for HIV or STDs. Multivariate analyses found that men who engaged in unprotected anal intercourse were more likely to have had sex with unknown status or HIV-infected partners; have sex while under the influence of drugs; tended to find partners on the internet; and were more likely to have a primary male partner. Men who were newly diagnosed with HIV or syphilis tended to be over 30 years old; had sex with an HIV-infected partner; had a prior STD diagnosis; and met partners on the internet. For 10.5% of the men, their HIV testing in the bathhouse was the first time that they had ever been screened for HIV. Of 24 men who were newly diagnosed with HIV infection, only one was not successfully linked to care. These data suggest that offering HIV and STD screening in a bathhouse setting is successful in attracting MSM who were at increased risk for HIV and/or STD acquisition or transmission, and may help decrease spread.
doi:10.1097/QAI.0b013e31823bbecf
PMCID: PMC3261361
PMID: 22027871
Sexually transmitted infections; HIV; sexual risk; men having sex with men (MSM); bathhouse
Eshleman, Susan H. | Hudelson, Sarah E. | Redd, Andrew D. | Wang, Lei | Debes, Rachel | Chen, Ying Q. | Martens, Craig A. | Ricklefs, Stacy M. | Selig, Ethan J. | Porcella, Stephen F. | Munshaw, Supriya | Ray, Stuart C. | Piwowar-Manning, Estelle | McCauley, Marybeth | Hosseinipour, Mina C. | Kumwenda, Johnstone | Hakim, James G. | Chariyalertsak, Suwat | de Bruyn, Guy | Grinsztejn, Beatriz | Kumarasamy, Nagalingeswaran | Makhema, Joseph | Mayer, Kenneth H. | Pilotto, Jose | Santos, Breno R. | Quinn, Thomas C. | Cohen, Myron S. | Hughes, James P.
Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events.
Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region).
Results. In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner’s HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established.
Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.
doi:10.1093/infdis/jir651
PMCID: PMC3209811
PMID: 21990420
Thirty years into the global HIV epidemic, the need for effective prevention strategies remains critical. In July 2010, the CAPRISA-004 study demonstrated that topical administration of a gel containing the antiretroviral agent tenofovir decreased the risk of HIV acquisition among at-risk heterosexual women. Subsequently, the iPrEx study reported that prophylactic use of a daily oral tablet containing tenofovir and emtricitabine reduced the risk of HIV acquisition among high-risk men who have sex with men. These studies illustrate the promise of antiretroviral pre-exposure chemoprophylaxis (PrEP) as an innovative prevention approach. This review discusses the rationale for chemoprophylaxis, compares the advantages of topical and oral delivery, outlines recommended safety monitoring, offers principles to guide selection of antiretroviral agents, and highlights potential unintended consequences of PrEP use. If future studies confirm the safety and efficacy of tenofovir gel and oral PrEP, successful implementation of these strategies could significantly impact the HIV epidemic.
doi:10.1007/s11904-011-0094-4
PMCID: PMC3240840
PMID: 22002729
HIV; Primary Prevention; Chemoprevention; Anti-HIV Agents; Reverse Transcriptase Inhibitors; Gels; HIV infections/prevention & control; Clinical Trial; Unsafe Sex
Abstract
A divide exists between categories of men who have sex with men (MSM) in India based on their sex position, which has consequences for the design of novel HIV prevention interventions. We examine the interaction between sex position and other attributes on existing HIV risk including previous HIV testing, unprotected anal intercourse (UAI), and HIV serostatus among MSM recruited from drop-in centers and public cruising areas in the twin cities of Hyderabad and Secunderabad, India. A survey was administered by trained research assistants and minimally invasive HIV testing was performed by finger-stick or oral testing. HIV seropositive MSM underwent CD4+ lymphocyte count measurement. In our sample (n=676), 32.6% of men were married to women, 22.2% of receptive only participants were married, and 21.9% of men were HIV seropositive. In bivariate analysis, sex position was associated with previous HIV testing, UAI, HIV serostatus, and CD4+ lymphocyte count at diagnosis. In multivariate analysis with interaction terms, dual unmarried men were more likely to have undergone an HIV test than insertive unmarried men (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.2–6.5), a relationship that did not hold among married men. Conversely, dual married men were less likely than insertive married men to engage in UAI (OR 0.3; 95% CI 0.1–0.6), a relationship that did not hold among unmarried men. Further implementation research is warranted in order to best direct novel biologic and behavioral prevention interventions towards specific risk behaviors in this and other similar contexts.
doi:10.1089/apc.2011.0079
PMCID: PMC3263302
PMID: 21682588
Goodreau, Steven M. | Carnegie, Nicole B. | Vittinghoff, Eric | Lama, Javier R. | Sanchez, Jorge | Grinsztejn, Beatriz | Koblin, Beryl A. | Mayer, Kenneth H. | Buchbinder, Susan P. | Sullivan, Patrick S.
In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru.
doi:10.1371/journal.pone.0050522
PMCID: PMC3510067
PMID: 23209768
African Americans face disproportionately higher risks of HIV infection. Concurrent sexual relationships, or sexual partnerships that overlap in time, are more common among African Americans than individuals of other races and may contribute to racial disparities in HIV infection. However, little is known about attitudes, norms and practices among individuals engaged in concurrent partnerships. Little is also known about the processes through which structural, behavioral and social factors influence concurrent sexual relationships. We recruited 24 heterosexual African American men involved in concurrent sexual relationships from a public health clinic in Philadelphia. We conducted in-depth interviews exploring these men's sexual practices; social norms and individual attitudes about concurrency; perceived sexual health risks with main and non-main partners; and the social, structural and behavioral factors contributing to concurrent sexual relationships. Twenty-two men reported having one main and one or more non-main partners; two reported having no main partners. Respondents generally perceived sexual relationships with non-main partners as riskier than relationships with main partners and used condoms far less frequently with main than non-main partners. Most participants commented that it is acceptable and often expected for men and women to engage in concurrent sexual relationships. Social factors influencing participants’ concurrent partnerships included being unmarried and trusting neither main nor non-main partners. Structural factors influencing concurrent partnerships included economic dependence on one or more women, incarceration, unstable housing, and unemployment. Several men commented that individual behavioral factors such as alcohol and cocaine use contributed to their concurrent sexual partnerships. Future research and interventions related to sexual concurrency should address social and structural factors in addition to conventional HIV risk-taking behaviors.
doi:10.1080/09540121.2011.565030
PMCID: PMC3202040
PMID: 21981345
A significant proportion of men engage in sexual relationships with other men which has direct health implications, but the unique health care needs of these patients are often ignored or overlooked. Moreover, due to a fear of stigmatization by the medical community, one of the more significant health risks for men who have sex with men (MSM) may be that they avoid routine or appropriate health care. Physicians and other providers can help overcome this barrier and improve the health care of MSM by keeping a non-judgmental attitude toward these patients, differentiating sexual behaviour from sexual identity, communicating with gender neutral terms, and maintaining awareness of how their own attitudes affect clinical judgment. The purpose of this article is to help contextualize health issues affecting MSM and provide a framework for physicians and other providers to deliver optimum and appropriate health care for men who have sex with men in India.
PMCID: PMC3516023
PMID: 23168696
HIV-1; MSM; primary care; sex behaviour; sexually transmitted infections
Objectives
To estimate the incidence of first-responder visits to emergency departments (EDs) for blood or body fluid exposures, elucidate any temporal patterns of these visits, and quantify human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) utilization for these exposures.
Methods
This was a retrospective study of first responders presenting to Rhode Island EDs for blood or body fluid exposures from 1995 to 2001. Incidence rates for exposures with 95% confidence intervals (CIs) were estimated. Temporal trends for visits were modeled. Factors associated with HIV PEP utilization were identified using logistic regression. Odds ratios (ORs) with 95% CIs were estimated.
Results
The average incidence rate of ED visits for blood or body fluid exposures was 23.29 (20.07--26.52) ED visits per 100,000 ambulance runs. The incidence rose between 1995 and 1999 and then decreased. First-responder ED visits were lowest in October and highest in April and were lowest at 7 AM and highest at 7 PM. First responders presenting with a percutaneous or blood-to-mucous membrane exposure had a 4.13 (1.82--8.89) greater odds and those exposed to a known HIV-infected source had a 9.03 (1.59--51.26) greater odds of being offered HIV PEP. First responders presenting to a teaching hospital had a 2.21 (1.02--4.77) greater odds of being offered prophylaxis and a 4.20 (1.08--16.32) greater odds of accepting prophylaxis when it was offered.
Conclusions
First responders face a risk of blood or body fluid exposure that varies over the course of the day and the year. HIV PEP is more likely to be used if the exposures are percutaneous, or blood-to-mucous membrane, or if the source is known to be HIV-infected. Standardization of protocols across EDs for administering HIV prophylaxis appears to be needed.
doi:10.1080/10903120802471931
PMCID: PMC3440874
PMID: 19145518
emergency medical technicians; needlestick injuries; occupational exposures; blood; blood-borne pathogens; disease transmission
Objectives
We assessed the extent to which Centers for Disease Control and Prevention (CDC) recommendations have influenced routine HIV testing among Massachusetts community health center (CHC) personnel, and identified specific barriers and facilitators to routine testing.
Methods
Thirty-one CHCs were enrolled in the study. We compared those that did and did not receive funding support from the federal Ryan White HIV/AIDS Program. An anonymous survey was administered to a maximum five personnel from each CHC, including a senior administrator, the medical director, and three medical providers. Overall, 137 participants completed the survey.
Results
Among all CHCs, 53% of administrators reported having implemented routine HIV testing at their CHCs; however, only 33% of medical directors/providers reported having implemented routine HIV testing in their practices (p<0.05). Among administrators, 60% of those from Ryan White-supported CHCs indicated that both they and their CHCs were aware of CDC's recommendations, compared with 27% of administrators from non-Ryan White-supported CHCs. The five most frequently reported barriers to the implementation of routine HIV testing were (1) constraints on providers' time (68%), (2) time required to administer counseling (65%), (3) time required to administer informed consent (52%), (4) lack of funding (35%), and (5) need for additional training (34%). In a multivariable logistic regression model, the provision of on-site HIV testing by nonmedical staff resulted in increased odds of conducting routine HIV testing (odds ratio [OR] = 9.84, 95% confidence interval [CI] 1.77, 54.70). However, the amount of time needed to administer informed consent was associated with decreased odds of providing routine testing (OR=0.21, 95% CI 0.05, 0.92).
Conclusions
Routine HIV testing is not currently being implemented uniformly among Massachusetts CHCs. Future efforts to increase implementation should address personnel concerns regarding time and staff availability.
PMCID: PMC3151181
PMID: 21886324
Kelley, Colleen F. | Haaland, Richard E. | Patel, Pragna | Evans-Strickfaden, Tammy | Farshy, Carol | Hanson, Debra | Mayer, Kenneth | Lennox, Jeffrey L. | Brooks, John T. | Hart, Clyde E.
Background. Among human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) taking combination antiretroviral therapy (cART), the impact of rectal sexually transmitted infections (STIs) on rectal HIV-1 shedding is unknown.
Methods. Human immunodeficiency virus type 1 (HIV-1) RNA was quantified from rectal swabs collected for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) screening of HIV-1-infected MSM. Correlations of STIs with rectal viral load were explored using multinomial regression modeling. HIV-1 coreceptor tropism was predicted from sequencing in a subset of men.
Results. Thirty-one (39%) of 80 men (59 prescribed combination antiretroviral therapy [cART]) had HIV detected in 38 (42%) of 91 rectal swabs. Rectal HIV detection was associated with plasma virus loads above 3.15 log10 copies/mL (95% confidence limit [CL] 2.73, 3.55) and paired rectal viral loads and plasma viral loads were correlated (Kendall’s tau [τ] 0.68, Spearman rho [P] = .77). Rectal STIs and abnormal anal cytology were not associated with rectal viral load. HIV coreceptor distribution was very similar between the plasma and rectum in 3 of 4 men.
Conclusions. Plasma and rectal viral load were correlated, and rectal STIs did not increase the likelihood of detecting HIV in the rectal secretions in MSM, including those with low or undetectable plasma viral load. Suppressing plasma viral load is likely to reduce risk of HIV transmission to insertive partners.
doi:10.1093/infdis/jir400
PMCID: PMC3156109
PMID: 21844302
In the United States, 10 million inmates are released every year, and human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) prevalence is several-fold greater in criminal justice populations than in the community. Few effective linkage-to-the-community programs are currently available for prisoners infected with HIV. As a result, combination antiretroviral therapy (cART) is seldom continued after release, and virological and immunological outcomes worsen. Poor HIV treatment outcomes result from a myriad of obstacles that released prisoners face upon reentering the community, including homelessness, lack of medical insurance, relapse to drug and alcohol use, and mental illness. This article will focus on 5 distinct factors that contribute significantly to treatment outcomes for released prisoners infected with HIV and have profound individual and public health implications: (1) adaptation of case management services to facilitate linkage to care; (2) continuity of cART; (3) treatment of substance use disorders; (4) continuity of mental illness treatment; and (5) reducing HIV-associated risk-taking behaviors as part of secondary prevention.
doi:10.1093/cid/cir446
PMCID: PMC3156144
PMID: 21844030
In India men who have sex with men (MSM) are a stigmatized and hidden population, vulnerable to a variety of psychosocial and societal stressors. This population is also much more likely to be HIV-infected compared to the general population. However, little research exists about how psychosocial and societal stressors result in mental health problems. A confidential, quantitative mental-health interview was conducted among 150 MSM in Mumbai, India at The Humsafar Trust, the largest non-governmental organization serving MSM in India. The interview collected information on sociodemographics and assessed self-esteem, social support and DSM-IV psychiatric disorders using the Mini International Neuropsychiatric Interview (MINI). Participants' mean age was 25.1 years (SD=5.1); 21% were married to women. Forty-five percent reported current suicidal ideation, with 66% low risk, 19% moderate risk, and 15% high risk for suicide per MINI guidelines. Twenty-nine percent screened in for current major depression and 24% for any anxiety disorder. None of the respondents reported current treatment for any psychiatric disorder. In multivariable models controlling for age, education, income and sexual identity, participants reporting higher levels of self-esteem and greater levels of satisfaction with the social support they receive from family and friends were at lower risk of suicidality (self-esteem AOR=0.85, 95% CI: 0.78-0.93; social support AOR=0.76, 95% CI: 0.62-0.93) and major depression (self-esteem AOR=0.79, 95% CI: 0.71-0.89; social support AOR=0.68, 95% CI: 0.54-0.85). Those who reported greater social support satisfaction were also at lower risk of a clinical diagnosis of an anxiety disorder (AOR=0.80; 95% CI: 0.65-0.99). MSM in Mumbai have high rates of suicidal ideation, depression and anxiety. Programs to improve self-esteem and perceived social support may improve these mental health outcomes. Because they are also a high-risk group for HIV, MSM HIV prevention and treatment services may benefit from incorporating mental health services and referrals into their programs.
doi:10.1080/13548506.2011.554645
PMCID: PMC3136931
PMID: 21749242
Men who have sex with men (MSM); Mumbai; India; mental health; suicide; depression; anxiety
Detels, Roger | Green, Annette M. | Klausner, Jeffrey D. | Katzenstein, David | Gaydos, Charlotte | Handsfield, H. Hunter | Pequegnat, Willo | Mayer, Kenneth | Hartwell, Tyler D. | Quinn, Thomas C.
Background
Asymptomatic Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infections pose diagnostic and control problems in developing countries.
Methods
Participants in China, India, Peru, Russia, and Zimbabwe were screened for C. trachomatis and N. gonorrhoeae infections and symptoms.
Results
A total of 18,014 participants were evaluated at baseline, 15,054 at 12 months, and 14,243 at 24 months. The incidence of chlamydia in men was 2.0 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 4.6 from baseline to 12 months and 3.6 from 12 to 24 months; a range of 31.2% to 100% reported no symptoms across the 5 countries. The incidence of gonorrhea in men was 0.3 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 1.4 from baseline to 12 months and 1.1 from 12 to 24 months; a range of 66.7% to 100% reported no symptoms. Being female, aged 18 to 24 years, and having more than 1 partner were associated with both the infections. In addition, being divorced, separated, or widowed was associated with gonorrhea. Being male, having 6+ years of education, and reporting only 1 partner were associated with having no symptoms among those infected with chlamydia. No variables correlated with asymptomatic gonorrhea among those infected.
Conclusion
A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings. More effective programs are needed to identify and treat chlamydia and gonorrhea infections, especially among women, young adults, those with multiple partners, those repeatedly infected, and particularly those at risk without symptoms. The risk of transmission from persons with no symptoms requires further study.
PMCID: PMC3408314
PMID: 22256336
Objective
We determine whether (1) an audiocomputer-delivered tailored feedback intervention increases emergency department (ED) patient uptake of opt-in, nontargeted rapid HIV screening; and (2) uptake is greater among patients who report more HIV risk and among those whose self-perceived HIV risk increases from baseline after completion of an HIV risk assessment.
Methods
ED patients aged 18 to 64 years were randomly assigned to receive either an assessment about reported and self-perceived HIV risk or an identical assessment plus feedback about their risk for having or acquiring an HIV infection, tailored according to their reported risk. All participants were offered a fingerstick rapid HIV test. Two-sample tests of binomial proportions were used to compare screening uptake by study arm. Multivariable logistic regression was used to assess the relationship of reported HIV risk and an increase in self-perceived HIV risk with uptake of HIV screening.
Results
Of the 566 participants, the median age was 29 years, 62.2% were women, and 66.9% previously had been tested for HIV. Uptake of HIV screening was similar in the intervention and no intervention arms (54.1% versus 55.5% [Δ =–0.01%; 95% confidence interval {CI} –0.09% to 0.07%]). An increase in self-perceived HIV risk predicted greater uptake of HIV screening for women (odds ratio 2.15; 95% CI 1.08 to 4.28) but not men (odds ratio 1.61; 95% CI 0.60 to 4.30). Uptake of HIV screening was not related to reported HIV risk.
Conclusion
Uptake of rapid HIV screening in the ED was not improved by this feedback intervention. Other methods need to be investigated to improve uptake of HIV screening by ED patients.
doi:10.1016/j.annemergmed.2011.03.035
PMCID: PMC3205940
PMID: 21684389
Lahey, Timothy | Ghosh, Mimi | Fahey, John V. | Shen, Zheng | Mukura, Lucy R. | Song, Yan | Cu-Uvin, Susan | Mayer, Kenneth H. | Wright, Peter F. | Kappes, John C. | Ochsenbauer, Christina | Wira, Charles R. | Kaul, Rupert
Background
We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.
Methods
CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200–500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.
Results
CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% showing wide variation between viral strains. Although there was broad CVL inhibition of most both laboratory-adapted and T/F virus strains, there was practically no inhibition of T/F strain RHPA.c, which was isolated from a woman newly infected via heterosexual intercourse. HIV disease progression, measured by declining CD4 T cell counts, resulted in a selective reduction in intrinsic anti-HIV activity in CVL that paralleled CVL decreases in human beta-defensin 2 and increases in Elafin and secretory leukocyte protease inhibitor. HIV disease progress predicted decreased CVL anti-HIV activity against both laboratory-adapted and T/F strains of HIV. Anti-HIV activity exhibited close associations with CVL levels of fourteen cytokines and chemokines.
Conclusions
Amid a multifaceted immune defense against HIV-1 and other sexually transmitted pathogens, HIV disease progression is associated with selective disturbances in both CVL anti-HIV activity and specific innate immune defenses in the human female reproductive tract (FRT). Overall, these studies indicate that innate immune protection in the FRT is compromised as women progress to AIDS.
doi:10.1371/journal.pone.0038100
PMCID: PMC3366961
PMID: 22675510
Venkatesh, Kartik K | Srikrishnan, AK | Safren, Steven A | Triche, Elizabeth W | Thamburaj, E | Prasad, Lakshmi | Lurie, Mark N | Kumar, M Suresh | Kumarasamy, N | Solomon, Suniti | Mayer, Kenneth H
The current study examines sexual behaviors among HIV-infected Indians in primary care, where access to highly active antiretroviral therapy (HAART) has recently increased. Between January to April 2008, we assessed the sexual behaviors of 247 HIV-infected South Indians in care. Multivariable logistic regression models were used to determine predictors of being in a HIV-seroconcordant primary relationship, being sexually active, and reporting unprotected sex. Over three-fourths (80%) of participants were HAART-experienced. Among the 58% of participants who were currently in a seroconcordant relationship, one-third were serodiscordant when first tested for HIV. Approximately two-thirds (63.2%) of participants were sexually active; 9.0% reported unprotected sex. In the multivariable analyses, participants who were in a seroconcordant primary relationship were more likely to have children, use alcohol, report unprotected sex, and have been enrolled in care for >12 months. Sexually active participants were more likely to be on HAART, have a prior tuberculosis diagnosis, test Herpes simplex type 2 antibody seropositive, and have low general health perceptions. Participants who reported unprotected sex were more likely to be in a seroconcordant relationship, be childless, want to have a child, and use alcohol. We did not document an association between HAART and unprotected sex. Among HIV-infected Indians in primary care, predictors of unprotected sex included alcohol use and desire for children. Prevention interventions for Indian couples should integrate reproductive health and alcohol use counseling at entry into care.
doi:10.1080/09540121.2010.525616
PMCID: PMC3095699
PMID: 21293990
HIV; AIDS; sexual behavior; HAART; India
Saravanan, Shanmugam | Madhavan, Vidya | Murugavel, Kailapuri G. | Balakrishnan, Pachamuthu | Solomon, Sunil Suhas | Umapathy, Shankarkumar | Kantor, Rami | Kumarasamy, Nagalingeswaran | Yepthomi, Tokugha | Smith, Davey M. | Mayer, Kenneth H | Solomon, Suniti
doi:10.1097/QAI.0b013e3182169050
PMCID: PMC3154011
PMID: 21775932
Pho, Mai T. | Swaminathan, Soumya | Kumarasamy, Nagalingeswaran | Losina, Elena | Ponnuraja, C. | Uhler, Lauren M. | Scott, Callie A. | Mayer, Kenneth H. | Freedberg, Kenneth A. | Walensky, Rochelle P. | Pai, Madhukar
Background
Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.
Methods
We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm3, and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).
Results
Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.
Conclusions
Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.
doi:10.1371/journal.pone.0036001
PMCID: PMC3340407
PMID: 22558301
Abstract
African Americans are disproportionately infected with HIV/AIDS. Despite Centers for Disease Control and Prevention (CDC) guidelines recommending routine opt-out testing for HIV, most HIV screening is based on self-perceived HIV risks. Philadelphia launched a rapid HIV testing program in seven public health clinics in 2007. The program provides free rapid oral HIV tests to all patients presenting for health services who provide informed consent. We analyzed demographic, risk behavior, and HIV serostatus data collected during the program between September 2007 and January 2009. We used multivariable logistic regression to estimate the association between behavioral and demographic factors and newly diagnosed HIV infection. Of the 5871 individuals testing for HIV, 47% were male, 88% were African American, and the mean age was 34.7 years. Overall HIV prevalence was 1.1%. All positive tests represented new HIV diagnoses, and 72% of individuals reported testing previously. Approximately 90% of HIV-positive individuals and 92% of individuals with more than five recent sex partners never, or only sometimes, used condoms. Two thirds of individuals testing positive and 87% of individuals testing negative assessed their own HIV risk as zero or low. Individuals reporting cocaine use and ever having a same sex partner both had 2.6 times greater odds of testing positive. Condom use in this population was low, even among high-risk individuals. Philadelphia's program successfully provided HIV testing to many underserved African Americans who underestimate their HIV risk. Our results nevertheless suggest greater efforts are needed to encourage more individuals to undergo HIV testing in Philadelphia, particularly those who have never tested.
doi:10.1089/apc.2010.0313
PMCID: PMC3068868
PMID: 21406004
Hoots, Brooke E. | Hudgens, Michael G. | Cole, Stephen R. | King, Caroline C. | Klein, Robert S. | Mayer, Kenneth H. | Rompalo, Anne M. | Sobel, Jack D. | Jamieson, Denise J. | Smith, Jennifer S.
Many studies have chronicled the “epidemiologic synergy” between human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). HIV adversely affects the natural history of HSV-2 and results in more frequent and severe HSV-2 reactivation. Few longitudinal studies, however, have examined whether HSV-2 is associated with increased HIV plasma viral loads or decreased CD4 counts. The authors estimated the effect of HSV-2 seropositivity on HIV RNA viral load and on CD4 count over time among 777 HIV-seropositive US women not receiving suppressive HSV-2 therapy in the HIV Epidemiology Research Study (1993–2000). Linear mixed models were used to assess the effect of HSV-2 on log HIV viral load and CD4 count/mm3 prior to widespread initiation of highly active antiretroviral therapy. Coinfection with HSV-2 was not associated with HIV RNA plasma viral loads during study follow-up. There was a statistically significant association between HSV-2 seropositivity and CD4 count over time, but this difference was small and counterintuitive at an increase of 8 cells/mm3 (95% confidence interval: 2, 14) per year among HSV-2-seropositive women compared with HSV-2-seronegative women. These data do not support a clinically meaningful effect of baseline HSV-2 seropositivity on the trajectories of HIV plasma viral loads or CD4 counts.
doi:10.1093/aje/kwq432
PMCID: PMC3105280
PMID: 21372062
CD4 lymphocyte count; herpes simplex; herpesvirus 2, human; HIV; viral load
Background
In 2010, the iPrEx trial demonstrated that oral antiretroviral pre-exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk men who have sex with men (MSM). The impact of iPrEx on PrEP knowledge and actual use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP awareness, interest and experience among at-risk MSM before and after iPrEx, and to determine demographic and behavioral factors associated with these measures.
Methods and Findings
Cross-sectional, national, internet-based surveys were administered to U.S. based members of the most popular American MSM social networking site 2 months before (n = 398) and 1 month after (n = 4 558) publication of iPrEx results. Comparisons were made between these samples with regards to PrEP knowledge, interest, and experience. Data were collected on demographics, sexual risk, and experience with post-exposure prophylaxis (PEP). Regression analyses were performed to identify factors associated with PrEP awareness, interest, and experience post-iPrEx. Most participants were white, educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited pre- and post-iPrEx (13% vs. 19%), whereas interest levels after being provided with a description of PrEP remained high (76% vs. 79%). PrEP use remained uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI 1.52–36.6) and PEP experience (OR 34.2; CI 13.3–88.4). PrEP interest was associated with older age (OR 1.01; CI 1.00–1.02), unprotected anal intercourse with ≥1 male partner in the prior 3 months (OR 1.40; CI 1.10–1.77), and perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13–1.27).
Conclusions
Among MSM engaged in online networking, awareness of PrEP was limited 1 month after the iPrEx data were released. Utilization was low, although some MSM who reported high-risk behaviors were interested in using PrEP. Studies are needed to understand barriers to PrEP utilization by at-risk MSM.
doi:10.1371/journal.pone.0033119
PMCID: PMC3314648
PMID: 22470438
HCV incidence from 1996-2008 among HIV-infected men in U.S. HIV therapeutic trials was 0.51 per 100 person-years. Incident HCV occurred primarily through non-parenteral means; 75% of seroconverters reported no drug injection. At-risk HIV-infected persons should have access to HCV surveillance
Background. Outbreaks of sexually transmitted hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)–infected men who have sex with men in Europe, Australia, and New York. Whether this is occurring across the United States is unknown.
Methods. We determined incidence of HCV infection during 1996–2008 among male participants of the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials cohort, a long-term study of HIV-infected persons randomized into selected US-based clinical trials. We evaluated associations with self-reported injection drug use (IDU), time-varying CD4+ cell count, and HIV RNA level with use of multivariate Poisson regression. No sexual or non-IDU risk factor data was available.
Results. A total of 1830 men had an initial negative HCV antibody test result and at least 1 subsequent HCV antibody test result, contributing >7000 person-years. At the time of the initial negative HCV antibody test result, 94% of men were receiving highly active antiretroviral therapy (HAART) and 6% reported current or prior IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100 person-years (95% confidence interval, .36–.70). Mean age at seroconversion was 46 years. Seroconversion was associated with IDU (25% of seroconverters reported IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity vs 21% at time of last negative antibody test result; P = .02) but not with CD4+ cell count.
Conclusions. Incident HCV infection occurs in HIV-infected men involved in US HIV therapeutic trials, primarily through nonparenteral means, despite engagement in care and HAART. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression. At-risk HIV-infected persons should have access to HCV surveillance.
doi:10.1093/cid/ciq201
PMCID: PMC3106260
PMID: 21282184
Mimiaga, Matthew J. | Noonan, Elizabeth | Donnell, Deborah | Safren, Steven A. | Koenen, Karestan C. | Gortmaker, Steven | O’Cleirigh, Conall | Chesney, Margaret A. | Coates, Thomas J. | Koblin, Beryl A. | Mayer, Kenneth H.
Background
Previous studies have found high rates of childhood sexual abuse (CSA) among US men who have sex with men (MSM). CSA history has been associated with a variety of negative effects later in life including behaviors that place MSM at greater risk for HIV acquisition and transmission. The present analysis is the first to examine the longitudinal association between CSA and HIV infection, unprotected anal sex, and serodiscordant unprotected anal sex, as well as mediators of these relationships among a large sample of HIV-uninfected MSM.
Methods
The EXPLORE Study was a behavioral intervention trial conducted in 6 US cities over 48 months with HIV infection as the primary efficacy outcome. Behavioral assessments were done every 6 months via confidential computerized assessments. Longitudinal regression models were constructed, adjusting for randomization arm, geographical location of study site, age at enrollment, education, and race/ethnicity.
Results
Of the 4295 participants enrolled, 39.7% had a history of CSA. Participants with a history of CSA [adjusted hazards ratio = 1.30, 95% confidence interval (CI): 1.02 to 1.69] were at increased risk for HIV infection over study follow-up. A significant association was seen between history of CSA and unprotected anal sex (adjusted odds ratio = 1.24, 95% CI: 1.12 to 1.36) and serodiscordant unprotected anal sex (adjusted odds ratio = 1.30, 95% CI: 1.18 to 1.43). Among participants reporting CSA, the EXPLORE intervention had no effect in reducing HIV infection rates. Participants reporting CSA were significantly more likely to have symptoms of depression and use nonprescription drugs.
Conclusions
A predictive relationship between a history of CSA and subsequent HIV infection was observed among this large sample of HIV-uninfected MSM. Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs. Future HIV prevention interventions should address the specific mental health concerns of MSM with a history of CSA.
doi:10.1097/QAI.0b013e3181a24b38
PMCID: PMC3292283
PMID: 19367173
child sexual abuse; EXPLORE; HIV; MSM; sexual risk taking