As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic.
Using the Internet to meet sexual partners is associated with increased HIV risk behavior, including substance use, sex with multiple or anonymous partners, and unprotected anal sex (UAS), among diverse samples of MSM, yet little is known about Internet use and HIV risk among Black MSM specifically. In 2008, a sample of 197 Black MSM completed an interviewer-administered assessment and voluntary HIV counseling and testing. One fifth of the sample (20 %) reported meeting a sexual partner via the Internet in the past 12 months. Men who met sexual partners over the Internet had significantly more male sex partners (M = 13.44, SD = 20.01) than men who did not meet partners in this manner (M = 4.11, SD = 4.14, p < 0.001) and reported significantly higher rates of UAS (p < 0.05). Adjusting for sociodemographic and other HIV-related covariates, factors significantly associated with the increased odds of engaging in at least one episode of UAS with a male partner in the past 12 months included: meeting sexual partners on the Internet, identifying as gay, and lower knowledge about HIV transmission. These findings highlight the unique HIV risk behaviors among Black MSM meeting sexual partners via the Internet and warrant tailoring of prevention activities to address the specific behaviors and social influences that may contribute to increased HIV spread among this population.
MSM; Internet; African American/Black; HIV; Sexual risk
Depression is highly comorbid with HIV and may contribute to increased sexual transmission risk behavior (TRB) amongst HIV-infected MSM, the largest risk group for HIV in the U.S. However, examinations of this effect are inconsistent. The present longitudinal analyses of 746 HIV-infected MSM is from a multi-site “prevention for positives” study. A non-linear association between depression and TRB emerged. Moderate levels of depression (compared to either low or high levels) were associated with a more modest decline in the odds of sexual risk behavior over 12-month follow-up. Assessing depression in HIV primary care settings may help to identify those at risk and integrating the treatment of depression in to secondary prevention and treatment initiatives may decrease the likelihood of sexual risk and help to contain the epidemic among MSM.
HIV prevention with positives; men who have sex with men; sexual risk; depression
This study found a high incidence of hepatitis C virus infection among a sample of human immunodeficiency virus–infected men who have sex with men engaged in primary care in Boston, Massachusetts, in the absence of traditional risk factors such as injection drug use.
Background. Sexually transmitted hepatitis C virus (HCV) infection is an emerging epidemic among human immunodeficiency virus (HIV)–infected men who have sex with men (MSM). HCV may be underrecognized in this population, historically thought to be at low risk.
Methods. We determined the prevalence and incidence of HCV among HIV-infected men at Fenway Health between 1997 and 2009. We describe characteristics associated with HCV.
Results. Of 1171 HIV-infected men, of whom 96% identify as MSM, 1068 (91%) were screened for HCV and 64 (6%) had a positive HCV antibody (Ab) result at initial screening. Among the 995 men whose initial HCV Ab result was negative, 62% received no further HCV Ab testing. Among the 377 men who had ≥1 additional HCV Ab test, 23 (6%) seroconverted over 1408 person-years, for an annualized incidence of 1.63 per 100 person-years (95% confidence interval, .97–2.30). Among the 87 HIV-infected MSM diagnosed with prevalent or incident HCV, 33% reported history of injection drug use, 46% noninjection drug use (NIDU), and 70% sexually transmitted infections (STIs). Sixty-four (74%) of HCV-infected MSM developed chronic HCV; 22 (34%) initiated HCV treatment and 13 (59%) of treated persons achieved a sustained virologic response (SVR).
Conclusions. Prevalent and incident HCV, primarily acquired through nonparenteral means, was common in this HIV-infected population despite engagement in care. STIs and NIDU were common among HIV/HCV-coinfected MSM. SVR rates were high among those who underwent HCV treatment. All sexually active and/or substance-using HIV-infected MSM should receive routine and repeated HCV screening to allow for early diagnosis and treatment of HCV.
HIV; hepatitis C virus; men who have sex with men; screening; incidence
Despite known benefits, only 19–28% of HIV-infected Americans are virologically suppressed (defined as ≤200 copies/mL). Engagement in HIV care represents a continuum from patients unaware they are infected to virological suppression. The electronic medical record of all newly diagnosed HIV-infected MSM seen at Fenway Health between 2000 and 2010 were reviewed. Patients were “engaged” if they had one negative HIV test and/or one physical exam within 24 months prior to their HIV diagnosis (n=291). All others were considered “new” (n=463). MSM engaged in care prior to HIV diagnosis were more often identified in acute retroviral syndrome or on routine screening, more rapidly linked to care, and less often diagnosed with a concomitant STI than those who were not engaged in care. Nearly 19% of all patients were diagnosed with AIDS the same time they were diagnosed with HIV. Blacks and those with higher CD4 counts at diagnosis were less likely to be virologically suppressed at 1 year. Between 2000 and 2010, patients retained in care were more likely to initiate ART and be virologically suppressed within 1 year independent of initial HIV viral load and CD4 count. Engagement in care prior to seroconversion influences important HIV outcomes. Programs that care for at risk populations should institute routine opt-out HIV testing and test-and-treat programs to optimize HIV care and prevention.
The cost-effectiveness of early antiretroviral therapy (ART) in persons infected with human immunodeficiency virus (HIV) in serodiscordant couples is not known. Using a computer simulation of the progression of HIV infection and data from the HIV Prevention Trials Network 052 study, we projected the cost-effectiveness of early ART for such persons.
For HIV-infected partners in serodiscordant couples in South Africa and India, we compared the early initiation of ART with delayed ART. Five-year and lifetime outcomes included cumulative HIV transmissions, life-years, costs, and cost-effectiveness. We classified early ART as very cost-effective if its incremental cost-effectiveness ratio was less than the annual per capita gross domestic product (GDP; $8,100 in South Africa and $1,500 in India), as cost-effective if the ratio was less than three times the GDP, and as cost-saving if it resulted in a decrease in total costs and an increase in life-years, as compared with delayed ART.
In South Africa, early ART prevented opportunistic diseases and was cost-saving over a 5-year period; over a lifetime, it was very cost-effective ($590 per life-year saved). In India, early ART was cost-effective ($1,800 per life-year saved) over a 5-year period and very cost-effective ($530 per life-year saved) over a lifetime. In both countries, early ART prevented HIV transmission over short periods, but longer survival attenuated this effect; the main driver of life-years saved was a clinical benefit for treated patients. Early ART remained very cost-effective over a lifetime under most modeled assumptions in the two countries.
In South Africa, early ART was cost-saving over a 5-year period. In both South Africa and India, early ART was projected to be very cost-effective over a lifetime. With individual, public health, and economic benefits, there is a compelling case for early ART for serodiscordant couples in resource-limited settings. (Funded by the National Institute of Allergy and Infectious Diseases and others.)
Purpose of review
Recent randomized controlled trials have demonstrated that HIV Pre-Exposure Prophylaxis (PrEP) can decrease HIV incidence among several at-risk populations, including men who have sex with men, serodiscordant couples, and heterosexual men and women. As PrEP is a biomedical intervention that requires clinical monitoring and a high level of medication adherence, maximizing the public health effectiveness of PrEP in real-world settings will require the training of a cadre of healthcare providers to prescribe PrEP. Therefore it is critical to understand provider knowledge, practices and attitudes towards PrEP prescribing, and to develop strategies for engaging and training providers to provide PrEP.
A limited number of studies have focused on PrEP implementation by healthcare providers. These studies suggest that some providers are knowledgeable about PrEP, but many are not, or express misgivings. Although many clinicians report willingness to provide PrEP, few have prescribed PrEP in clinical practice. Provider comfort and skills in HIV risk assessment are suboptimal, which could limit identification of individuals who are most likely to benefit from PrEP use.
Further studies to understand facilitators and barriers to HIV risk assessment and PrEP prescribing by practicing clinicians are needed. Innovative training strategies and decision-support interventions for providers could optimize PrEP implementation and therefore merit additional research.
HIV; Prevention; Pre-Exposure Prophylaxis; Provider; Implementation
HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ∼2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.
Upon HIV transmission, many – though not all – immune escape mutations selected in the previous host will revert to the consensus residue. The persistence of certain escape mutations following transmission has led to concerns that these could gradually accumulate in circulating HIV sequences over time, thereby undermining host antiviral immune potential as the epidemic progresses. As certain immune-driven mutations reduce viral fitness, their spread through the population could also have consequences for the average replication capacity and/or protein function of circulating HIV sequences. Here, we characterized HIV sequences, linked to host immunogenetic information, from patients enrolled in historic (1979–1989) and modern (2000–2011) HIV cohorts from four key cities in the North American epidemic. We reconstructed the epidemic's ancestral (founder) HIV sequence and assessed the subsequent extent to which known HIV immune escape mutations have spread in the population. Our data support the gradual spread of many - though not all - immune escape mutations in HIV sequences over time, but to an extent that is unlikely to have major immediate immunologic consequences for the North American epidemic. Notably, in vitro assessments of ancestral and patient-derived HIV sequences suggested functional implications of ongoing HIV evolution for certain viral proteins.
A study of HIV-infected persons in primary care in four U.S. found that 13% had a prevalent STD at enrollment and 7% an incident STD six months later.
To better understand the factors associated with HIV and STD transmitting behavior among HIV-infected persons, we estimated STD prevalence and incidence and associated risk factors among a diverse sample of HIV-infected patients in primary care.
We analyzed data from 557 participants in the SUN study, a prospective observational cohort of HIV-infected persons in primary care in four U.S. cities. At enrollment and six months thereafter, participants completed an audio computer-assisted self interview about their sexual behavior, and were screened for genitourinary, rectal and pharyngeal N. gonorrhoeae and C. trachomatis infections by nucleic acid amplification testing, and for serologic evidence of syphilis. Women provided cervicovaginal samples and men provided urine to screen for T. vaginalis by polymerase chain reaction.
Thirteen percent of participants had a prevalent STD at enrollment and 7% an incident STD six months later. The most commonly diagnosed infections were rectal chlamydia, oropharyngeal gonorrhea, and chlamydial urethritis among the men, and trichomoniasis among the women. Other than trichomoniasis, 94% of incident STDs were identified in MSM. Polysubstance abuse other than marijuana, and having ≥ 4 sex partners in the six months prior to testing were associated with diagnosis of an incident STD.
STDs were commonly diagnosed among contemporary HIV-infected patients receiving routine outpatient care, particularly among sexually active MSM who used recreational drugs. These findings underscore the need for frequent STD screening, prevention counseling, and substance abuse treatment for HIV-infected persons in care.
HIV infection; sexual risk; sexually transmitted infections
The AIDS epidemic has been fueled by global inequities. Ranging from gender inequality and underdevelopment to homophobia impeding health care access for men who have sex with men (MSM), imbalanced resource allocations and social biases have potentiated the epidemic’s spread. However, recognition of culturally specific aspects of each microepidemic has yielded development of community-based organizations, which have resulted in locally effective responses to AIDS. This effective approach to HIV prevention, care and treatment is illustrated through examples of community-based responses in Haiti, the United States, Africa, and other impoverished settings.
Disparities; Inequity; Health Care Access; Homophobia; Gender Inequality
In addition to protecting against HIV acquisition, antiretroviral preexposure prophylaxis (PrEP) using topical 1% tenofovir gel reduced Herpes simplex virus type 2 (HSV-2) acquisition by 51% among women in the CAPRISA 004 study. We examined the effect of daily oral emtricitabine/tenofovir (FTC/TDF) PrEP on HSV-2 seroincidence and ulcer occurrence among men who have sex with men (MSM) in the iPrEx trial.
HSV-2 serum testing was performed at screening and every six months. Among HSV-2-seronegative individuals, we used Cox regression models to estimate hazard ratios (HRs) of HSV-2 seroincidence associated with randomization to FTC/TDF. We used multiple imputation and Cox regression to estimate HRs for HSV-2 seroincidence accounting for drug exposure. We assessed ulcer occurrence among participants with prevalent or incident HSV-2 infection.
Of the 2,499 participants, 1383 (55.3%) tested HSV-2-seronegative at baseline, 892 (35.7%) tested positive, 223 (8.9%) had indeterminate tests, and one test was not done. Of the 1,347 HSV-2-seronegative participants with follow-up, 125 (9.3%) had incident HSV-2 infection (5.9 per 100 person-years). Compared with participants receiving placebo, there was no difference in HSV-2 seroincidence among participants receiving FTC/TDF (HR 1.1, 95% CI: 0.8–1.5; P = 0.64) or among participants receiving FTC/TDF with a concentration of tenofovir diphosphate >16 per million viable cells (HR 1.0, 95% CI: 0.3–3.5; P = 0.95). Among participants with HSV-2 infection, the proportion with ≥1 moderate or severe ulcer adverse event was twice as high in the placebo vs. active arm (5.9% vs. 2.9%, P = 0.02), but there were no differences in the proportions with ≥1 clinical examination during which perianal or groin ulcers were identified.
Tenofovir in daily oral FTC/TDF PrEP may reduce the occurrence of ulcers in individuals with HSV-2 infection but does not protect against HSV-2 incidence among MSM.
Although the association of stimulant use to sexual risk taking and HIV transmission has been well documented among white gay men, stimulant use during sex continues to be under-explored among Black men who have sex with men (MSM).
Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and optional HIV counseling and testing. Bivariate logistic regression procedures were employed to examine the association of demographics, sexual risk, and other psychosocial factors with stimulant use (at least monthly during sex in the past 12 months). Variable elimination using the backward selection process was used to fit two separate final multivariable logistic regression models examining stimulant use as the outcome and HIV sexual risk in the past 12 months by gender as the primary predictor: (1) Model 1: HIV sexual risk behavior with a casual male sex partner as a primary, forced predictor; (2) Model 2: HIV sexual risk behavior with a female sex partner as primary, forced predictor.
One-third (34%) of Black MSM reported using stimulants monthly or more frequently during sex in the past 12 months. The following factors were independently associated with stimulant use during sex: (1) Model 1: unprotected anal sex with a casual male sex partner in the past 12 months (AOR = 2.61; 95% CI = 1.06–6.42; p = 0.01), older age (AOR = 1.09; 95% CI = 1.05–1.15; p < 0.001), erectile dysfunction (ED) medication use monthly or more during sex in the past 12 months (AOR = 7.81; 95% CI = 1.46–41.68; p = 0.02), problematic alcohol use (AOR = 3.31; 95% CI = 1.312–8.38; p = 0.005), and higher HIV treatment optimism (AOR = 0.86; 95% CI = 0.76–0.97; p = 0.01). (2) Model 2: unprotected vaginal or anal sex with a female partner in the past 12 months (AOR = 3.54; 95% CI = 1.66–7.56; p = 0.001), older age (AOR = 1.10; 95% CI = 1.05–1.14; p < 0.001), ED use monthly or more during sex in the past 12 months (AOR = 3.70; 95% CI = 1.13–12.13; p = 0.03), clinically significant depressive symptoms (CES-D) at the time of study enrollment (AOR = 3.11; 95% CI = 1.45–6.66; p = 0.004), and supportive condom use norms (AOR = 0.69; 95% CI = 0.49–0.97; p = 0.03).
Frequent stimulant use is an important factor in HIV and STD sexual risk among Black MSM, particularly for older men and those with co-occurring psychosocial morbidities. HIV and STD prevention interventions in this population may benefit from addressing the precipitants of stimulant use and sexual risk taking.
Stimulant use; Black; MSM; HIV; Sexual risk behavior
High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score ≥ 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16–26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches.
MSM; Depression; African American; HIV; STD
The Center for the AIDS Programme of Research in South Africa (CAPRISA) 004 and Pre-exposure Prophylaxis Initiative (iPrEx) studies demonstrated that topical or oral chemoprophylaxis could decrease HIV transmission. Yet to have an appreciable public health impact, physicians will need to be educated about these new HIV prevention modalities. Massachusetts physicians were recruited via e-mail to complete an online survey of their knowledge and use of HIV prevention interventions. Data were collected before (July–December, 2010) (n=178) and after (December, 2010–April, 2011) (n=115) the release of iPrEx data. Over the two time intervals, knowledge of oral PrEP significantly increased (79% to 92%, p<0.01), whereas knowledge about topical microbicides was already high (89% pre-iPrEx). Post-iPrEx, specialists were more knowledgeable about oral PrEP (p<0.01) and topical microbicides (p<0.001) than generalists. The majority of the respondents would prefer to prescribe topical microbicides (75%) than oral PrEP (25%; p<0.001), primarily because they perceived fewer side effects (95%). Respondents indicated that PrEP should be available if it were a highly effective, daily pill; however, ongoing concerns included: potential drug resistance (93%), decreased funds for other forms of HIV prevention (88%), medication side effects (83%), and limited data regarding PrEP's clinical efficacy (75%). Participants indicated that formal CDC guidelines would have the greatest impact on their willingness to prescribe PrEP (96%). Among Massachusetts physicians sampled, chemoprophylaxis knowledge was high, but current experience was limited. Although topical gel was preferred, responses suggest a willingness to adapt practices pending additional efficacy data and further guidance from normative bodies. Educational programs aimed at incorporating antiretroviral chemoprophylaxis into physicians' HIV prevention practices are warranted.
Men who have sex with men (MSM) are the largest group of individuals in the U.S. living with HIV and have the greatest number of new infections. This study was designed to test a brief, culturally relevant prevention intervention for HIV-infected MSM, which could be integrated into HIV care.
HIV-infected MSM who received HIV care in a community health center (N = 201), and who reported HIV sexual transmission-risk behavior (TRB) in the prior 6 months, were randomized to receive the intervention or treatment as usual. The intervention, provided by a medical social worker, included proactive case management for psychosocial problems, counseling about living with HIV, and HIV TRB risk reduction. Participants were followed every 3 months for one year.
Participants, regardless of study condition, reported reductions in HIV TRB, with no significant differential effect by condition in primary intent-to-treat analyses. When examining moderators, the intervention was differentially effective in reducing HIV TRB for those who screened in for baseline depression, but this was not the case for those who did not screen in for depression.
The similar level of reduction in HIV TRB in the intervention and control groups, consistent with other recent secondary prevention interventions, speaks to the need for new, creative designs, or more potent interventions in secondary HIV prevention trials, as the control group seemed to benefit from risk assessment, study contact, and referrals provided by study staff. The differential finding for those with depression may suggest that those without depression could reap benefits from limited interventions, but those with a comorbid psychiatric diagnosis may require additional interventions to modify their sexual risk behaviors.
MSM; HIV prevention; AIDS/HIV; high-risk sexual behavior; depression
American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood.
Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV.
HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6th (16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p<0.001); less likely to be living with a primary partner (p<0.001); more likely to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.011) or chlamydia (p = 0.020). Compared to HIV-uninfected Black MSM, ND were more likely to report unprotected receptive anal intercourse (URAI) with a male partner in the last 6 months (p<0.001); and to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.004), and urethral (p = 0.025) or rectal chlamydia (p<0.001). They were less likely to report female (p = 0.002) or transgender partners (p = 0.018). Multivariate logistic regression analyses found that ND Black MSM were significantly more likely than HIV-uninfected peers to be unemployed; have STIs, and engage in URAI. Almost half the men in each group were poor, had depressive symptoms, and expressed internalized homophobia.
ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community.
With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition.
HIV prevention; Pre-exposure prophylaxis; Microbicide; Tenofovir; Emtricitabine
New HIV infections among younger men who have sex with men (MSM) in the United States are escalating. Data on HIV infections in college students are limited. In 2010, three MSM college students presented to our clinic with primary HIV infection (PHI) in a single month. To determine the number of college students among new HIV diagnoses, we reviewed clinical characteristics and molecular epidemiology of HIV-diagnosed individuals from January to December 2010 at the largest HIV clinic in Southern New England. PHI was defined as acute HIV infection or seroconversion within the last 6 months. Of 66 individuals diagnosed with HIV in 2010, 62% were MSM and 17% were academic students (12% college or university, 5% other). Seventy-three percent of students were MSM. Compared to nonstudents, students were more likely to be younger (24 versus 39 years), born in the United States (91% versus 56%), have another sexually transmitted disease (45% versus 11%), and present with PHI (73% versus 16%, all p-values<0.05). Thirty percent of individuals formed eight transmission clusters including four students. MSM were more likely to be part of clusters. Department of Health contact tracing of cluster participants allowed further identification of epidemiological linkages. Given these high rates of PHI in recently diagnosed students, institutions of higher education should be aware of acute HIV presentation and the need for rapid diagnosis. Prevention strategies should focus on younger MSM, specifically college-age students who may be at increased risk of HIV infection.
This study evaluated whether specific anxiety disorders increased the likelihood of sexual transmission risk behavior (TRB) in younger (ages 20–29) versus older (ages 30+) HIV positive gay and bisexual men. Participants completed screening measures for Posttraumatic Stress Disorder (PTSD), Social Phobia, and Panic Disorder, and an assessment of recent TRB Moderated regression analyses indicated that PTSD was associated with greater risk of TRB in younger but not older men, independent of HIV disease stage or treatment status. Efficacy of secondary HIV prevention efforts for younger men may be augmented by addressing the context of trauma history and consequent mental health issues.
HIV; age; post-traumatic stress disorder; sexual transmission risk behavior
A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers.
Methods and Findings
Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA.
The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.
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.
Sexually transmitted infections; HIV; sexual risk; men having sex with men (MSM); bathhouse
Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.
Design and methods
Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy.
Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12).
There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.
Malnutrition is associated with morbidity and mortality in HIV infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression.
Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m2 less than that of patients who did not use any drugs, after adjusting for other covariates (p= 0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m2 less than that of patients under the age of 35, and BMI increased by 0.3 kg/m2 with each 100 cells/mm3 increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model.
In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.
drug users; cocaine users; BMI; HIV; CD4 count
HIV type-1 (HIV-1) monitoring in resource limited settings relies on clinical and immunological assessment. The objective of this study was to study the frequency and pattern of reverse transcriptase (RT) drug resistance among patients with immunological failure (IF) to first-line therapy.
A cross-sectional study of 228 patients with IF was done, of which 126 were drug-naive (group A) when starting highly active antiretroviral therapy (HAART) and 102 were exposed to mono/dual therapy prior to HAART initiation (group B). A validated in-house genotyping method and Stanford interpretaion was used. Means, sd, median and frequencies (as percentages) were used to indicate the patient characteristics in each group. The χ2 test and Fisher's exact test were used to compare categorical variables as appropriate. All analyses were performed using SPSS software, version 13.0. P-values <0.05 were considered to be statistically significant.
RT drug resistance mutations were found in 92% and 96% of patients in groups A and B, respectively. Median (interquartile range) CD4+ T–cell count at failure was 181cells/ml (18–999) and time to failure was 40 months (2–100). M184V (80% versus 75%), thymidine analogue mutations (63% versus 74%), Y181C (39% versus 39%) and K103N (29% versus 39%) were predominant RT mutations in both groups. Extensive nucleoside reverse transcriptase inhibitor cross-resistance mutations were observed in 51% and 26%of patients in group B and A, respectively.
Alternative strategies for initial therapy and affordable viral load monitoring could reduce resistance accumulations and preserve available drugs for future options in resource-limited settings.
Crystal methamphetamine use is a major driver behind high-risk sexual behavior among men who have sex with men (MSM). Prior work suggests a cycle of continued crystal methamphetamine use and high-risk sex due to loss of the ability to enjoy other activities, which appears to be a side effect of this drug. Behavioral activation (BA) is a treatment for depression that involves learning to reengage in life's activities. We evaluated a novel intervention for crystal methamphetamine abuse and high-risk sex in MSM, incorporating 10 sessions of BA with integrated HIV risk reduction counseling (RR). Forty-four subjects were screened, of whom 21 met initial entry criteria. A total of 19 participants enrolled; 16 completed an open-phase study of the intervention. Behavioral assessments were conducted at baseline, 3 months postbaseline, and 6 months postbaseline. Linear mixed effects regression models were fit to assess change over time. Mean unprotected anal intercourse (UAI) episodes decreased significantly from baseline to acute postintervention (β=−4.86; 95% confidence interval [CI]=−7.48, −2.24; p=0.0015) and from baseline to 6 months postbaseline (β=−5.07; 95% CI=−7.85, −2.29; p=0.0017; test of fixed effects χ2=16.59; df=2,13; p=0.0002). On average, there was a significant decrease over time in the number of crystal methamphetamine episodes in the past 3 months (χ2=22.43; df=2,15; p<0.0001), and the number of days of crystal methamphetamine use in the past 30 days (χ2=9.21; df=2,15; p=0.010). Statistically significant reductions in depressive symptoms and poly-substance use were also maintained. Adding behavioral activation to risk reduction counseling for MSM with problematic crystal methamphetamine use may augment the potency of a risk reduction intervention for this population. Due to the small sample size and time intensive intervention, future testing in a randomized design is necessary to determine efficacy, with subsequent effectiveness testing.