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Background: Black and Hispanic men have the highest rates of HIV diagnoses. To decrease the number of U.S. men who are unaware of their HIV status, they should be tested at least once. Our objective was to estimate the increases needed in HIV testing rates at ambulatory health care visits to achieve universal coverage., Methods: We analyzed nationally representative medical record abstraction data to estimate the number of visits per person to physician offices, emergency departments, and outpatient clinics among men aged 18-39 years during 2009-2016, and the percentage of visits with an HIV test. We calculated the increase in the percentage of visits with an HIV test needed to achieve universal testing coverage of men by age 39 years., Results: Men had a mean of 75.3 million ambulatory visits per year and 1.67 visits per person. An HIV test was performed at 0.9% of the ambulatory visits made by white men, 2.5% by black men, and 2.4% by Hispanic men. A 3-fold increase in the percentage of visits with an HIV test would result in coverage of 46.2% of white, 100% of black, and 100% of Hispanic men; an 11-fold increase would be needed to result in coverage of 100% of white men., Conclusions: HIV testing rates of men at ambulatory health care visits were too low to provide HIV testing coverage of all men by aged 39 years. A 3-fold increase in the percentage of visits with an HIV test would result in universal testing coverage of black and Hispanic men by age 39 years., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Female genital schistosomiasis (FGS) affects up to 56 million women in sub-Saharan Africa and may increase risk of HIV infection., Methods: To assess the association of schistosomiasis with HIV infection, peer-reviewed literature published until 31 December 2018 was examined and a pooled estimate for the odds ratio was generated using Bayesian random effects models., Results: Of the 364 abstracts that were identified, 26 were included in the summary. Eight reported odds ratios of the association between schistosomiasis and HIV; one reported a transmission hazard ratio of 1.8 (95% CI, 1.2-2.6) among women and 1.4 (95% CI, 1.0-1.9) among men; 11 described the prevalence of schistosomiasis among HIV-positive people (range, 1.5-36.6%); and six reported the prevalence of HIV among people with schistosomiasis (range, 5.8-57.3%). Six studies were selected for quantitative analysis. The pooled estimate for the odds ratio of HIV among people with schistosomiasis was 2.3 (95% CI, 1.2-4.3)., Conclusions: A significant association of schistosomiasis with HIV was found. However, a specific summary estimate for FGS could not be generated. A research agenda was provided to determine the effect of FGS on HIV infection. The WHO's policy on mass drug administration for schistosomiasis may prevent HIV., (Published by Elsevier Ltd.)

We sought to integrate a brief computer and counseling support intervention into the routine practices of HIV clinics and evaluate effects on patients' viral loads. The project targeted HIV patients in care whose viral loads exceeded 1000 copies/ml at the time of recruitment. Three HIV clinics initiated the intervention immediately, and three other HIV clinics delayed onset for 16 months and served as concurrent controls for evaluating outcomes. The intervention components included a brief computer-based intervention (CBI) focused on antiretroviral therapy adherence; health coaching from project counselors for participants whose viral loads did not improve after doing the CBI; and behavioral screening and palm cards with empowering messages available to all patients at intervention clinics regardless of viral load level. The analytic cohort included 982 patients at intervention clinics and 946 patients at control clinics. Viral loads were assessed at 270 days before recruitment, at time of recruitment, and +270 days later. Results indicated that both the control and intervention groups had significant reductions in viral load, ending with approximately the same viral level at +270 days. There was no evidence that the CBI or the targeted health coaching was responsible for the viral reduction in the intervention group. Results may stem partially from statistical regression to the mean in both groups. Also, clinical providers at control and intervention clinics may have taken action (e.g., conversations with patients, referrals to case managers, adherence counselors, mental health, substance use specialists) to help their patients reduce their viral loads. In conclusion, neither a brief computer-based nor targeted health coaching intervention reduced patients' viral loads beyond levels achieved with standard of care services available to patients at well-resourced HIV clinics.

Objective: Sexual HIV transmission is more likely to occur when plasma HIV RNA level (viral load) exceeds 1500 copies/ml. We assessed the percentage of person-time spent with viral load above 1500 copies/ml (pPT >1500) among adults with HIV in care., Design: Observational cohort in eight United States HIV clinics., Methods: Participants had at least one HIV Outpatient Study (HOPS) clinic visit and at least two viral loads during 2000-2014. We assessed pPT above 1500 in time intervals between consecutive viral load pairs, overall and by ART status. Trends in pPT above 1500 and associations between pPT above 1500 and chosen baseline demographics and clinical characteristics were analyzed using generalized estimating equations., Results: There were 5873 patients contributing 37 794 person-years; 86.0% person-years had prescribed ART, with increasing coverage over time. Over 2000-2014 pPT above 1500 was 24.2%, decreasing from 38.3% in 2000-2002 to 11.3% in 2012-2014. During observation time with ART prescribed, pPT above 1500 was 16.4% overall, decreasing from 29.9% in 2000-2002 to 8.0% in 2012-2014. pPT above 1500 was higher in patients less than 35 vs. at least 50 years old (31.5 vs. 15.6%), women vs. men (30.8 vs. 22.3%), and black vs. white and Latino/Hispanic patients (32.7 vs. 19.9 and 23.7%, respectively). Multivariable correlates of higher pPT above 1500 included no prescribed ART, being younger, non-Hispanic black vs. white, baseline viral load above 1500 copies/ml or lower CD4 count, and baseline public vs. private insurance., Conclusion: pPT above 1500 declined during 2000-2014. Results support decreasing HIV transmission risk from persons in HIV care over the last decade, and the need to focus interventions on patient groups more consistently viremic.

Objective: To appropriately identify and treat noncommunicable diseases (NCDs) among persons living with HIV (PLHIV) in low-and-middle-income countries (LMICs), it is imperative to understand the burden of NCDs among PLHIV in LMICs and the current management of the diseases., Design: Systematic review and meta-analysis., Methods: We examined peer-reviewed literature published between 1 January 2010 and 31 December 2016 to assess currently available evidence regarding HIV and four selected NCDs (cardiovascular disease, cervical cancer, depression, and diabetes) in LMICs with a focus on sub-Saharan Africa. The databases, PubMed/MEDLINE, Cochrane Review, and Scopus, were searched to identify relevant literature. For conditions with adequate data available, pooled estimates for prevalence were generated using random fixed effects models., Results: Six thousand one hundred and forty-three abstracts were reviewed, 377 had potentially relevant prevalence data and 141 were included in the summary; 57 were selected for quantitative analysis. Pooled estimates for NCD prevalence were hypertension 21.2% (95% CI 16.3-27.1), hypercholesterolemia 22.2% (95% CI 14.7-32.1), elevated low-density lipoprotein 23.2% (95% CI 15.2-33.6), hypertriglyceridemia 27.2% (95% CI 20.7-34.8), low high-density lipoprotein 52.3% (95% CI 35.6-62.8), obesity 7.8% (95% CI 4.3-13.9), and depression 24.4% (95% CI 12.5-42.1). Invasive cervical cancer and diabetes prevalence were 1.3-1.7 and 1.3-18%, respectively. Few NCD-HIV integrated programs with screening and management approaches that are contextually appropriate for resource-limited settings exist., Conclusion: Improved data collection and surveillance of NCDs among PLHIV in LMICs are necessary to inform integrated HIV/NCD care models. Although efforts to integrate care exist, further research is needed to optimize the efficacy of these programs.

Background: In 2014, women represented 19% of HIV diagnoses in the United States. Of these, 78% were among black women and Latinas. Sexual risk behaviors-for example concurrent sex partnerships, nonmonogamous sex partners, and inconsistent condom use-are associated with increased HIV transmission and prevalence; these behaviors have been understudied, collectively, in women., Methods: To examine HIV-related sexual risk behaviors among sexually active women aged 18-44 years by race/ethnicity and over time, we used data from the 2006-2008, 2008-2010, and 2011-2013 cycles of the National Survey of Family Growth. We estimated weighted percentages and performed logistic regression to measure adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between selected behaviors and sociodemographic covariates., Results: Among 13,588 women, 1.1% reported concurrent sex partnerships, 10.3% reported male partners whom they perceived were nonmonogamous, and 21.1% reported using a condom at either last vaginal or anal sex. Black women (aPR = 1.52; CI = 1.36-1.71) and Latinas (aPR = 1.29; CI = 1.14-1.47) were more likely to report condom use at either last vaginal or anal sex compared with white women. However, black women were also more likely to report concurrent opposite-sex partnerships (aPR = 2.44; CI = 1.57-3.78) and perceived nonmonogamous sex partners (aPR = 1.33; CI = 1.14-1.56) compared with white women., Conclusions: Improved HIV behavioral risk-reduction strategies are needed for women. Black women could benefit from interventions that address partnership concurrency. For black women and Latinas, who are more likely to use condoms, further examination of broader social and structural factors as contributors to racial/ethnic gaps are warranted and vital for understanding and decreasing HIV-related disparities.

Background: HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT)., Methods: We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per μL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02515149., Findings: We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2·14, 95% CI 1·67-2·74; log rank p<0·0001)., Interpretation: Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care., Funding: US Centers for Disease Control and Prevention., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: CD4+ T-lymphocyte count testing at the point-of-care (POC) may improve linkage to care of persons diagnosed with HIV-1 infection, but the accuracy of POC devices when operated by lay-counselors in the era of task-shifting is unknown. We examined the accuracy of Alere's Pima™ POC device on both capillary and venous blood when performed by lay-counselors and laboratory technicians., Methods: In Phase I, we compared the perfomance of POC against FACSCalibur™ for 280 venous specimens by laboratory technicians. In Phase II we compared POC performance by lay-counselors versus laboratory technicians using 147 paired capillary and venous specimens, and compared these to FACSCalibur™. Statistical analyses included Bland-Altman analyses, concordance correlation coefficient, sensitivity, and specificity at treatment eligibility thresholds of 200, 350, and 500cells/μl., Results: Phase I: POC sensitivity and specificity were 93.0% and 84.1% at 500cells/μl, respectively. Phase II: Good agreement was observed for venous POC results from both lay-counselors (concordance correlation coefficient (CCC)=0.873, bias -86.4cells/μl) and laboratory technicians (CCC=0.920, bias -65.7cells/μl). Capillary POC had good correlation: lay-counselors (CCC=0.902, bias -71.2cells/μl), laboratory technicians (CCC=0.918, bias -63.0cells/μl). Misclassification at the 500 cells/μl threshold for venous blood was 13.6% and 10.2% for lay-counselors and laboratory technicians and 12.2% for capillary blood in both groups. POC tended to under-classify the CD4 values with increasingly negative bias at higher CD4 values., Conclusions: Pima™ results were comparable to FACSCalibur™ for both venous and capillary specimens when operated by lay-counselors. POC CD4 testing has the potential to improve linkage to HIV care without burdening laboratory technicians in resource-limited settings., (Published by Elsevier B.V.)

Background: Women who inject drugs and who also exchange sex are at increased risk for HIV infection, but data on this population in the United States remain sparse., Methods: This study assessed the prevalence of exchanging sex for money or drugs among women who inject drugs using data from the 2009 US National HIV Behavioral Surveillance (NHBS) system. Prevalence of being HIV-positive (testing positive in NHBS), HIV-positive-unaware (reporting being HIV-negative or unknown status but testing positive in NHBS), and risk behaviors and use of services were compared between women who did and did not exchange sex. The association between exchange sex and being HIV-positive-unaware of the infection was examined using multivariate Poisson models with robust standard errors., Results: Among 2305 women who inject drugs, 39% reported receiving things like money or drugs from ≥1 male partners in exchange for oral, vaginal, or anal sex in the previous 12 months. Women who exchanged sex were more likely to be unemployed, homeless, lack health insurance, have multiple condomless vaginal or anal sex partners, and receptively share syringes. In multivariate analysis, exchange sex was associated with being HIV-positive-unaware (adjusted prevalence ratio 1.97, 95% confidence intervals: 1.31 to 2.97)., Conclusions: Prevalence of exchange sex was high in this population. Women who exchange sex were more likely to be socially disadvantaged, report sexual and injection risk, and be HIV-positive-unaware. They represent an important group to reach with HIV prevention, testing, and care services.

Objective: A recent HIV outbreak in a rural network of persons who inject drugs (PWID) underscored the intersection of the expanding epidemics of opioid abuse, unsterile injection drug use (IDU), and associated increases in hepatitis C virus (HCV) infections. We sought to identify US communities potentially vulnerable to rapid spread of HIV, if introduced, and new or continuing high rates of HCV infections among PWID., Design: We conducted a multistep analysis to identify indicator variables highly associated with IDU. We then used these indicator values to calculate vulnerability scores for each county to identify which were most vulnerable., Methods: We used confirmed cases of acute HCV infection reported to the National Notifiable Disease Surveillance System, 2012-2013, as a proxy outcome for IDU, and 15 county-level indicators available nationally in Poisson regression models to identify indicators associated with higher county acute HCV infection rates. Using these indicators, we calculated composite index scores to rank each county's vulnerability., Results: A parsimonious set of 6 indicators were associated with acute HCV infection rates (proxy for IDU): drug-overdose deaths, prescription opioid sales, per capita income, white, non-Hispanic race/ethnicity, unemployment, and buprenorphine prescribing potential by waiver. Based on these indicators, we identified 220 counties in 26 states within the 95th percentile of most vulnerable., Conclusions: Our analysis highlights US counties potentially vulnerable to HIV and HCV infections among PWID in the context of the national opioid epidemic. State and local health departments will need to further explore vulnerability and target interventions to prevent transmission.

Background: The HIV continuum of care paradigm uses a single viral load test per patient to estimate the prevalence of viral suppression. We compared this single-value approach with approaches that used multiple viral load tests to examine the stability of suppression., Methods: The retrospective analysis included HIV patients who had at least 2 viral load tests during a 12-month observation period. We assessed the (1) percent with suppressed viral load (<200 copies/mL) based on a single test during observation, (2) percent with suppressed viral loads on all tests during observation, (3) percent who maintained viral suppression among patients whose first observed viral load was suppressed, and (4) change in viral suppression status comparing first with last measurement occasions. Prevalence ratios compared demographic and clinical subgroups., Results: Of 10,942 patients, 78.5% had a suppressed viral load based on a single test, whereas 65.9% were virally suppressed on all tests during observation. Of patients whose first observed viral load was suppressed, 87.5% were suppressed on all subsequent tests in the next 12 months. More patients exhibited improving status (13.3% went from unsuppressed to suppressed) than worsening status (5.6% went from suppressed to unsuppressed). Stable suppression was less likely among women, younger patients, black patients, those recently diagnosed with HIV, and those who missed ≥1 scheduled clinic visits., Conclusions: Using single viral load measurements overestimated the percent of HIV patients with stable suppressed viral load by 16% (relative difference). Targeted clinical interventions are needed to increase the percent of patients with stable suppression.

Objectives: As trials were assessing the safety and efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for the prevention of HIV infection, there was a clear need to understand the evolution of knowledge of, and attitudes toward, PrEP among primary care clinicians., Methods: Physicians and nurse practitioners were surveyed in 2009 (n = 1500), 2010 (n = 1504), 2012 (n = 1503), 2013 (n = 1507), 2014 (n = 1508) and 2015 (n = 1501) to assess their awareness of PrEP, willingness to prescribe PrEP, and whether they support use of public funds to pay for PrEP. Pharmacists (n = 251) were surveyed about PrEP in 2012 only. Descriptive statistics were computed for physician demographics and PrEP-related questions. Prevalence ratios for willingness to prescribe PrEP were computed using Poisson regression analysis., Results: Awareness of PrEP was low among clinicians (2009: 24%, 2010: 29%) but increased after trials reported effectiveness (2012: 49%, 2013: 51%, 2014: 61%, 2015: 66%). Following a description of PrEP with an estimated effectiveness of 75%, across 6 of the study years 91% of clinicians indicated a willingness to prescribe PrEP to at least one group at high risk of HIV acquisition. A smaller majority of clinicians indicated support for public funding of PrEP in 2009: 59%, 2010: 53%, and 2013: 63%., Conclusions: In surveys conducted before and after the release of PrEP trial results, primary care clinicians were largely unaware of PrEP. They indicated high levels of willingness to prescribe it for patients at high risk of HIV acquisition and expressed interest in education about how to deliver this new clinical HIV prevention method. It will be important to continue monitoring clinician knowledge, attitudes, and practices as the use of PrEP increases in the US.

Background: Over half of human immunodeficiency virus (HIV) infections in the United States occur among men who have sex with men (MSM). Among MSM, 16% of estimated new infections in 2010 occurred among black MSM <25 years old., Methodology: We analyzed National HIV Behavioral Surveillance data on MSM from 20 cities. Poisson models were used to test racial disparities, by age, in HIV prevalence, HIV awareness, and sex behaviors among MSM in 2014. Data from 2008, 2011, and 2014 were used to examine how racial/ethnic disparities changed across time., Results: While black MSM did not report greater sexual risk than other MSM, they were most likely to be infected with HIV and least likely to know it. Among black MSM aged 18-24 years tested in 2014, 26% were HIV positive. Among white MSM aged 18-24 years tested in 2014, 3% were HIV positive. The disparity in HIV prevalence between black and white MSM increased from 2008 to 2014, especially among young MSM., Conclusions: Disparities in HIV prevalence between black and white MSM continue to increase. Black MSM may be infected with HIV at younger ages than other MSM and may benefit from prevention efforts that address the needs of younger men., (Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: Testing for human immunodeficiency virus (HIV) is the key first step in HIV treatment and prevention. In 2006, the Centers for Disease Control and Prevention (CDC) recommended annual HIV testing for people at high risk for HIV infection. We evaluated HIV testing among men with high-risk heterosexual (HRH) contact and sexually active men who have sex with men (MSM) before and after the CDC recommendations., Methods: We used data from the National Survey of Family Growth, 2002 and 2006-2010, to assess proportions of HRH respondents and MSM reporting HIV testing in the prior 12 months, compare rates of testing before and after release of the 2006 CDC HIV testing guidelines, and examine demographic variables and receipt of health-care services as correlates of HIV testing., Results: Among MSM, the proportion tested was 37.2% (95% confidence interval [CI] 28.2, 47.2) in 2002, 38.2% (95% CI 25.9, 52.2) in 2006-2008, and 41.7% (95% CI 29.2, 55.3) in 2008-2010; among HRH respondents, the proportion was 23.7% (95% CI 20.5, 27.3) in 2002, 24.5% (95% CI 20.9, 28.7) in 2006-2008, and 23.9% (95% CI 20.2, 28.1) in 2008-2010. HIV testing was more likely among MSM and HRH respondents who received testing or treatment for sexually transmitted disease in the prior 12 months, received a physical examination in the prior 12 months (MSM only), or were incarcerated in the prior 12 months., Conclusions: The rate of annual HIV testing was low for men with sexual risk for HIV infection, and little improvement took place from 2002 to 2006-2010. Interventions aimed at men at risk, especially MSM, in both nonmedical and health-care settings, likely could increase HIV testing.

Context: HIV incidence is increasing among 13-24-year-old U.S. men who have sex with men, yet limited research is available to guide HIV prevention efforts for this population., Methods: National Survey of Family Growth data collected in 2002, in 2006-2010 and in 2011-2013 from 8,068 males aged 15-24 were analyzed to describe the population of U.S. young sexual minority males (i.e., males reporting same-sex attraction, identity or behavior). Correlates of sexual minority classification were assessed in logistic regression models., Results: An estimated 10% of young males, representing a population of 2.1 million, were sexual minorities. Males had an elevated likelihood of being sexual minorities if they were aged 18-19 or 20-24, rather than 15-17 (prevalence ratio, 1.7 for each); belonged to nonblack, non-Hispanic racial or ethnic minority groups (1.6); had no religious affiliation, rather than considering religion very important (1.9); or lived below the federal poverty level (1.3). They had a reduced likelihood of being sexual minorities if they lived in metropolitan areas outside of central cities (0.7). Among young sexual minority males, 44% were 15-19 years old, 29% were poor and 59% resided outside central cities. Forty-seven percent had engaged in same-sex behavior. Of those with data on all measured dimensions of sexuality, 24% reported same-sex attraction, identity and behavior; 22% considered themselves heterosexual, yet had had a male sex partner., Conclusion: Future investigations can further explore subpopulations of young sexual minority males and assess sexual trajectories, resilience and HIV risk., (Copyright © 2016 by the Guttmacher Institute.)

Objective: In recent HIV intervention trials, intervention efficacies appear to decline over time. Researchers have attributed this to "waning," or a loss of intervention efficacy. Another possible reason is heterogeneity in infection risk or "frailty." We propose an approach to assessing the impact of frailty and waning on measures of intervention efficacy and statistical power in randomized-controlled trials., Methods: Using multiplicative risk reduction, we developed a mathematical formulation for computing disease incidence and the incidence rate ratio (IRR) as a function of frailty and waning. We designed study scenarios, which held study-related factors constant, varied waning and frailty parameters and measured the change in disease incidence, IRR, and statistical power., Results: We found that frailty alone can impact disease incidence over time. However, frailty has minimal impact on the IRR. The factor that has the greatest influence on the IRR is intervention efficacy and the degree to which it is projected to wane. We also found that even moderate waning can cause an unacceptable decrease in statistical power while the impact of frailty on statistical power is minimal., Discussion: We conclude that frailty has minimal impact on trial results relative to intervention efficacy. Study resources would, therefore, be better spent on efforts to keep the intervention efficacy constant throughout the trial (e.g., enhancing the vaccine schedule or promoting treatment adherence).

We examined differences in HIV-infected U.S.-born and foreign-born black mothers who delivered perinatally HIV-exposed and -infected children during 1995-2004 in the Pediatric Spectrum of HIV Disease Project, a longitudinal cohort study. Prevalence ratios were calculated to explain differences in perinatal HIV prevention opportunities comparing U.S.-born to foreign-born and African-born to Caribbean-born black mothers. U.S.-born compared with foreign-born HIV-infected black mothers were significantly more likely to have used cocaine or other non-intravenous illicit drugs, exchanged money or drugs for sex, known their HIV status before giving birth, received intrapartum antiretroviral (ARV) prophylaxis, and delivered a premature infant; and were significantly less likely to have received prenatal care or delivered an HIV-infected infant. African-born compared with Caribbean-born black mothers were more likely to receive intrapartum ARV prophylaxis. These differences by maternal geographical origin have important implications for perinatal HIV transmission prevention, and highlight the validity of disaggregating data by racial/ethnic subgroups.

HIV RNA viral load (VL) is a pivotal outcome variable in studies of HIV infected persons. We propose and investigate two frameworks for analyzing VL: (1) a single-measure VL (SMVL) per participant and (2) repeated measures of VL (RMVL) per participant. We compared these frameworks using a cohort of 720 HIV patients in care (4,679 post-enrollment VL measurements). The SMVL framework analyzes a single VL per participant, generally captured within a "window" of time. We analyzed three SMVL methods where the VL binary outcome is defined as suppressed or not suppressed. The omit-participant method uses a 8-month "window" (-6/+2 months) around month 24 to select the participant's VL closest to month 24 and removes participants from the analysis without a VL in the "window". The set-to-failure method expands on the omit-participant method by including participants without a VL within the "window" and analyzes them as not suppressed. The closest-VL method analyzes each participant's VL measurement closest to month 24. We investigated two RMVL methods: (1) repeat-binary classifies each VL measurement as suppressed or not suppressed and estimates the proportion of participants suppressed at month 24, and (2) repeat-continuous analyzes VL as a continuous variable to estimate the change in VL across time, and geometric mean (GM) VL and proportion of participants virally suppressed at month 24. Results indicated the RMVL methods have more precision than the SMVL methods, as evidenced by narrower confidence intervals for estimates of proportion suppressed and risk ratios (RR) comparing demographic strata. The repeat-continuous method had the most precision and provides more information than other considered methods. We generally recommend using the RMVL framework when there are repeated VL measurements per participant because it utilizes all available VL data, provides additional information, has more statistical power, and avoids the subjectivity of defining a "window."

Objective: We examined HIV transmission potential of patients in care by analyzing the amount of person-time spent above a viral load threshold that increases risk for transmission., Design: Observational cohort and supplemental data., Methods: The cohort included HIV patients who received care at six HIV clinics in the United States, from 1 April 2009 to 31 March 2013, and had two or more viral load tests during this interval. Person-time (in days) above a viral load of 1500 copies/ml out of the total observation time was determined by inspecting consecutive pairs of viral load results and the time intervals between those pairs. The person-time rate ratios comparing demographic and clinical subgroups were estimated with Poisson regression., Results: The cohort included 14 532 patients observed for a median of 1073 days with a median of nine viral load records. Ninety percent of the patients had been prescribed antiretroviral therapy. On average, viral load exceeded 1500 copies/ml during 23% of the patients' observation time (average of 84 days per year, per patient). Percentage of person-time above the threshold was higher among patients who had more than a fourth of their viral load pairs exceeding a 6-month interval (34% of observation time), patients not on antiretroviral therapy (58% of time), new/re-engaging patients (34% of time), patients 16-39 years of age (32% of time), and patients of black race (26% of time)., Conclusion: HIV patients in care spent an average of nearly a quarter of their time with viral loads above 1500 copies/ml, higher among some subgroups, placing them at risk for potentially transmitting HIV to others.

This study examined study product adherence and its determinants in the Botswana oral pre-exposure prophylaxis efficacy trial. Among the 1,219 participants, the mean adherence by pill count and 3-day self-report was 94 % for each. In multivariable models, pill count adherence was significantly associated with adverse events (nausea, dizziness, vomiting) (RR 0.98 95 % CI 0.98-1.00; p = 0.03) and side effect concerns (RR 0.98 95 % CI 0.96-0.99; p = 0.01). Self-reported adherence was significantly associated with having an HIV-positive partner (RR 1.02 95 % CI 1.00-1.04; p = 0.02) and Francistown residence (RR 0.98 95 % CI 0.96, 0.99; p = 0.0001). Detectable drug concentrations showed modest associations with self-report and pill count adherence, and drug levels were higher among those self-reporting 100 % adherence than those reporting <100 %. Most common adherence barriers involved refill delays and other logistic challenges; cellphone alarm reminder use was the most common facilitator.

Objective: To incorporate preexposure prophylaxis and other biomedical or intensive behavioral interventions into the care of injection drug users (IDUs), health care providers need validated, rapid, risk screening tools for identifying persons at highest risk of incident HIV infection., Methods: To develop and validate a brief screening tool for assessing the risk of contracting HIV (ARCH), we included behavioral and HIV test data from 1904 initially HIV-uninfected men and women enrolled and followed in the AIDS Linked to the Intravenous Experience prospective cohort study between 1988 and 2008. Using logistic regression analyses with generalized estimating equations, we identified significant predictors of incident HIV infection, then rescaled and summed their regression coefficients to create a risk score., Results: The final logistic regression model included age, engagement in a methadone maintenance program, and a composite injection risk score obtained by counting the number of the following 5 behaviors reported during the past 6 months: injection of heroin, injection of cocaine, sharing a cooker, sharing needles, or visiting a shooting gallery. The area under the receiver operating characteristic curve was 0.720; possible scores on the index ranged from 0 to 100 and a score 46 or greater had a sensitivity of 86.2% and a specificity of 42.5%, appropriate for a screening tool., Discussion: We developed an easy to administer 7-question screening tool with a cutoff that is predictive of incident HIV infection in a large prospective cohort of IDUs in Baltimore. The ARCH-IDUs screening tool can be used to prioritize persons who are injecting illicit drugs for consideration of preexposure prophylaxis and other intensive HIV prevention efforts.

Importance: Human immunodeficiency virus (HIV) transmission risk is primarily dependent on behavior (sexual and injection drug use) and HIV viral load. National goals emphasize maximizing coverage along the HIV care continuum, but the effect on HIV prevention is unknown., Objectives: To estimate the rate and number of HIV transmissions attributable to persons at each of the following 5 HIV care continuum steps: HIV infected but undiagnosed, HIV diagnosed but not retained in medical care, retained in care but not prescribed antiretroviral therapy, prescribed antiretroviral therapy but not virally suppressed, and virally suppressed., Design, Setting, and Participants: A multistep, static, deterministic model that combined population denominator data from the National HIV Surveillance System with detailed clinical and behavioral data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project to estimate the rate and number of transmissions along the care continuum. This analysis was conducted January 2013 to June 2014. The findings reflect the HIV-infected population in the United States in 2009., Main Outcomes and Measures: Estimated rate and number of HIV transmissions., Results: Of the estimated 1,148,200 persons living with HIV in 2009, there were 207,600 (18.1%) who were undiagnosed, 519,414 (45.2%) were aware of their infection but not retained in care, 47,453 (4.1%) were retained in care but not prescribed ART, 82,809 (7.2%) were prescribed ART but not virally suppressed, and 290,924 (25.3%) were virally suppressed. Persons who are HIV infected but undiagnosed (18.1% of the total HIV-infected population) and persons who are HIV diagnosed but not retained in medical care (45.2% of the population) were responsible for 91.5% (30.2% and 61.3%, respectively) of the estimated 45,000 HIV transmissions in 2009. Compared with persons who are HIV infected but undiagnosed (6.6 transmissions per 100 person-years), persons who were HIV diagnosed and not retained in medical care were 19.0% (5.3 transmissions per 100 person-years) less likely to transmit HIV, and persons who were virally suppressed were 94.0% (0.4 transmissions per 100 person-years) less likely to transmit HIV. Men, those who acquired HIV via male-to-male sexual contact, and persons 35 to 44 years old were responsible for the most HIV transmissions by sex, HIV acquisition risk category, and age group, respectively., Conclusions and Relevance: Sequential steps along the HIV care continuum were associated with reduced HIV transmission rates. Improvements in HIV diagnosis and retention in care, as well as reductions in sexual and drug use risk behavior, primarily for persons undiagnosed and not receiving antiretroviral therapy, would have a substantial effect on HIV transmission in the United States.

Objective: We derived an estimate of male condom effectiveness during anal sex among men who have sex with men (MSM) because the most widely used estimate of condom effectiveness (80%) was based on studies of persons during heterosexual sex with an HIV-positive partner., Design: Assessed male condom effectiveness during anal sex between MSM in 2 prospective cohort studies of HIV incidence by self-reported consistency of use., Methods: Analyzed data combined from US participants in the EXPLORE trial (1999-2001) public use data set and in the VAX 004 trial (1998-1999) data set. Initially, HIV-uninfected MSM enrolled in these trials completed baseline and semiannual interviews about their sexual behaviors with male partners and underwent HIV testing. Using a time-to-event model, effectiveness of consistent condom use in preventing HIV infection was estimated among men reporting receptive and/or insertive anal sex with an HIV-positive partner and consistency of condom use., Results: Among MSM reporting any anal sex with an HIV-positive male partner, we found 70% effectiveness with reported consistent condom use (compared with never use) and no significant protection when comparing sometimes use to never use. This point estimate for MSM was less than the 80% effectiveness estimate reported for heterosexuals in HIV-discordant couples reporting consistent condom use. However, the point estimates in the 2 populations are not statistically different. Only 16% of MSM reported consistent condom use during anal sex with male partners of any HIV status over the entire observation period., Conclusions: These estimates are useful for counseling efforts and for modeling the impact and comparative effectiveness of condoms and other prevention methods used by MSM.

Background: Prevention of sexually acquired HIV infection now includes both consistent condom use and daily use of oral antiretroviral preexposure prophylaxis (PrEP). Persons at substantial HIV risk can now use one or both prevention methods, but a combined HIV protective effect has not been assessed., Methods: We use deterministic models to examine the impact of method adherence and rates of PrEP and male condom use on number of anticipated HIV infections. Analyses were based on hypothetical cohorts of 10,000 African American men who have sex with men (AAMSM), a population with the highest HIV incidence in the United States. Parameters used in the model (condom effectiveness, PrEP effectiveness, HIV incidence) were based on published findings., Results: Among AAMSM who never use PrEP, an estimated 323 annual HIV infections would occur among those who always use condoms, 1007 among sometimes condom users, and 1094 among never condoms users. Among AAMSM who never (or inconsistently) use condoms, 295 (272) infections would occur among those who report at least 90% PrEP adherence and 744 (684) infection occur with less than 50% adherence. Among AAMSM who are consistently (or sometimes) taking PrEP, the highest protection is seen with consistent condom use, 87 (220) HIV infections and 92.0% (79.9%) prevention effectiveness., Discussion: Among AAMSM with inconsistent or never condom use, the addition of PrEP at either modest or high adherence can increase HIV protection. For consistent condom users, any PrEP use can increase HIV protection. These analyses provide an approach for rethinking HIV risk management by calculating combined HIV protective effects of using one or more effective prevention methods.

According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: Thirty-six months of isoniazid preventive therapy (36IPT) was superior to 6 months of IPT (6IPT) in preventing tuberculosis (TB) among HIV-infected adults in Botswana. We assessed the posttrial durability of this benefit., Design: A 36-month double-blind placebo controlled trial (1 : 1 randomization) with recruitment between November 2004 and July 2006 and observation until June 2011., Methods: One thousand, nine hundred and ninety-five participants were followed in eight public health clinics. Twenty-four percent had a tuberculin skin test ≥5 mm (TST-positive). A minimum CD4 lymphocyte count was not required for enrolment. Antiretroviral therapy (ART) was provided in accordance with Botswana guidelines; 72% of participants retained by June 2011 had initiated ART. Multivariable analysis using Cox regression analysis included treatment arm, TST status, ART as a time-dependent variable and CD4 cell count at baseline and updated at 36 months., Results: In the posttrial period, 2.13 and 2.14 per 100 person-years accumulated, whereas 0.93 and 1.13% TB incidence rates were observed in the 36IPT and 6IPT arms, respectively (P = 0.52). The crude hazard ratio of TB during the trial and posttrial was 0.57 [95% confidence intervals (CI) 0.33, 0.99] and 0.82 (95% CI 0.46, 1.49), and when restricted to TST-positive participants was 0.26 (95% CI 0.08, 0.80) and 0.40 (95% CI 0.15, 1.08), respectively. Multivariable analysis showed that ART use was associated with reduced death (adjusted hazard ratio 0.36, 95% CI 0.17-0.75) but not TB (0.92, 95% CI 0.55-1.53) in the posttrial period., Conclusion: The benefit of 36IPT for TB prevention declined posttrial in this cohort. Adjunctive measures are warranted to prevent TB among HIV-infected persons receiving long-term ART in TB-endemic settings., Competing Interests: The authors have no conflicts of interest to declare.

Objectives: We estimated HIV prevalence and risk factors among persons receiving mental health treatment in Philadelphia, Pennsylvania, and Baltimore, Maryland, January 2009 to August 2011., Methods: We used a multisite, cross-sectional design stratified by clinical setting. We tested 1061 individuals for HIV in university-based inpatient psychiatric units (n = 287), intensive case-management programs (n = 273), and community mental health centers (n = 501)., Results: Fifty-one individuals (4.8%) were HIV-infected. Confirmed positive HIV tests were 5.9% (95% confidence interval [CI] = 3.7%, 9.4%) for inpatient units, 5.1% (95% CI = 3.1%, 8.5%) for intensive case-management programs, and 4.0% (95% CI = 2.6%, 6.1%) for community mental health centers. Characteristics associated with HIV included Black race, homosexual or bisexual identity, and HCV infection., Conclusions: HIV prevalence for individuals receiving mental health services was about 4 times as high as in the general population. We found a positive association between psychiatric symptom severity and HIV infection, indicating that engaging persons with mental illness in appropriate mental health treatment may be important to HIV prevention. These findings reinforce recommendations for routine HIV testing in all clinical settings to ensure that HIV-infected persons receiving mental health services are identified and referred to timely infectious disease care.

Nationally representative data from the 2007 National Health Interview Survey (NHIS) were used to compare HIV testing prevalence among US adults with mental illness (schizophrenia spectrum disorder, bipolar disorder, depression, and/or anxiety) to those without, providing an update of prior work using 1999 and 2002 NHIS data. Logistic regression modeling was used to estimate the probability of ever being tested for HIV by mental illness status, adjusting for age, sex, race/ethnicity, marital status, substance abuse, excessive alcohol or tobacco use, and HIV risk factors. Based on data from 21,785 respondents, 15% of adults had a psychiatric disorder and 37% ever had an HIV test. Persons with schizophrenia (64%), bipolar disorder (63%), and depression and/or anxiety (47%) were more likely to report ever being tested for HIV than those without mental illness (35%). In multivariable models, individuals reporting schizophrenia (adjusted prevalence ratio=1.68, 95% confidence interval=1.33-2.13), bipolar disease (1.58, 1.39-1.81), and depression and/or anxiety (1.31, 1.25-1.38) were more likely to be tested for HIV than persons without these diagnoses. Similar to previous analyses, persons with mental illness were more likely to have been tested than those without mental illness. However, the elevated prevalence of HIV in populations with mental illness suggests that high levels of testing along with other prevention efforts are needed.

In 2011, 62% of estimated new HIV diagnoses in the United States were attributed to male-to-male sexual contact (men who have sex with men, MSM); 39% of these MSM were black or African American. HIV testing, recommended at least annually by CDC for sexually active MSM, is an essential first step in HIV care and treatment for HIV-positive individuals. A variety of HIV testing initiatives, designed to reach populations disproportionately affected by HIV, have been developed at both national and local levels. We assessed changes in HIV testing behavior among MSM participating in the National HIV Behavioral Surveillance System in 2008 and 2011. We compared the percentages tested in the previous 12 months in 2008 and 2011, overall and by race/ethnicity and age group. In unadjusted analyses, recent HIV testing increased from 63% in 2008 to 67% in 2011 overall (P<0.001), from 63% to 71% among black MSM (P<0.001), and from 63% to 75% among MSM of other/multiple races (P<0.001); testing did not increase significantly for white or Hispanic/Latino MSM. Multivariable model results indicated an overall increase in recent HIV testing (adjusted prevalence ratio [aPR] = 1.07, P<0.001). Increases were largest for black MSM (aPR = 1.12, P<0.001) and MSM of other/multiple races (aPR = 1.20, P<0.001). Among MSM aged 18-19 years, recent HIV testing was shown to increase significantly among black MSM (aPR = 1.20, P = 0.007), but not among MSM of other racial/ethnic groups. Increases in recent HIV testing among populations most affected by HIV are encouraging, but despite these increases, improved testing coverage is needed to meet CDC recommendations.

Background: The aim of the study was to determine whether enhanced personal contact with human immunodeficiency virus (HIV)-infected patients across time improves retention in care compared with existing standard of care (SOC) practices, and whether brief skills training improves retention beyond enhanced contact., Methods: The study, conducted at 6 HIV clinics in the United States, included 1838 patients with a recent history of inconsistent clinic attendance, and new patients. Each clinic randomized participants to 1 of 3 arms and continued to provide SOC practices to all enrollees: enhanced contact with interventionist (EC) (brief face-to-face meeting upon returning for care visit, interim visit call, appointment reminder calls, missed visit call); EC + skills (organization, problem solving, and communication skills); or SOC only. The intervention was delivered by project staff for 12 months following randomization. The outcomes during that 12-month period were (1) percentage of participants attending at least 1 primary care visit in 3 consecutive 4-month intervals (visit constancy), and (2) proportion of kept/scheduled primary care visits (visit adherence)., Results: Log-binomial risk ratios comparing intervention arms against the SOC arm demonstrated better outcomes in both the EC and EC + skills arms (visit constancy: risk ratio [RR], 1.22 [95% confidence interval {CI}, 1.09-1.36] and 1.22 [95% CI, 1.09-1.36], respectively; visit adherence: RR, 1.08 [95% CI, 1.05-1.11] and 1.06 [95% CI, 1.02-1.09], respectively; all Ps < .01). Intervention effects were observed in numerous patient subgroups, although they were lower in patients reporting unmet needs or illicit drug use., Conclusions: Enhanced contact with patients improved retention in HIV primary care compared with existing SOC practices. A brief patient skill-building component did not improve retention further. Additional intervention elements may be needed for patients reporting illicit drug use or who have unmet needs., Clinical Trials Registration: CDCHRSA9272007., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Accurate clinical laboratory reference values derived from a local or regional population base are required to correctly interpret laboratory results. In Botswana, most reference intervals used to date are not standardized across clinical laboratories and are based on values derived from populations in the United States or Western Europe., Methods: We measured 14 hematologic and biochemical parameters of healthy young adults screened for participation in the Botswana HIV Pre-exposure Prophylaxis Study using tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) (TDF2 Study). Reference intervals were calculated using standard methods, stratified by gender, and compared with the site-derived reference values used for the TDF2 study (BOTUSA ranges), the Division of AIDS (DAIDS) Grading Table for Adverse Events, the Botswana public health laboratories, and other regional references., Results: Out of 2533 screened participants, 1786 met eligibility criteria for participation in study and were included in the analysis. Our reference values were comparable to those of the Botswana public health system except for amylase, blood urea nitrogen (BUN), phosphate, total and direct bilirubin. Compared to our reference values, BOTUSA reference ranges would have classified participants as out of range for some analytes, with amylase (50.8%) and creatinine (32.0%) producing the highest out of range values. Applying the DAIDS toxicity grading system to the values would have resulted in 45 and 18 participants as having severe or life threatening values for amylase and hemoglobin, respectively., Conclusion: Our reference values illustrate the differences in hematological and biochemical analyte ranges between African and Western populations. Thus, the use of western-derived reference laboratory values to screen a group of Batswana adults resulted in many healthy people being classified as having out-of-range blood analytes. The need to establish accurate local or regional reference values is apparent and we hope our results can be used to that end in Botswana.

We examined CD4 cell count and plasma viral load patterns among Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2 study) participants who seroconverted, comparing participants assigned to receive tenofovir/emtricitabine with participants assigned to receive placebo. We also evaluated for antiretroviral drug resistance among the breakthrough HIV infections. Among nine seroconverters assigned to tenofovir/emtricitabine and 24 to placebo, there were no significant differences in their CD4 cell count or viral load profiles over time. Of the four participants who seroconverted on-study while receiving tenofovir/emtricitabine, none became infected as a result of drug-resistant HIV; moreover, no resistance mutations emerged following seroconversion.

Over half of HIV infections in the United States occur among men who have sex with men (MSM). Awareness of infection is a necessary precursor to antiretroviral treatment and risk reduction among HIV-infected persons. We report data on prevalence and awareness of HIV infection among MSM in 2008 and 2011, using data from 20 cities participating in the 2008 and 2011 National HIV Behavioral Surveillance System (NHBS) among MSM. Venue-based, time-space sampling was used to recruit men for interview and HIV testing. We analyzed data for men who reported ≥ 1 male sex partner in the past 12 months. Participants who tested positive were considered to be aware of their infection if they reported a prior positive HIV test. We used multivariable analysis to examine differences between results from 2011 vs. 2008. HIV prevalence was 19% in 2008 and 18% in 2011 (p = 0.14). In both years, HIV prevalence was highest among older age groups, blacks, and men with lower education and income. In multivariable analysis, HIV prevalence did not change significantly from 2008 to 2011 overall (p = 0.51) or in any age or racial/ethnic category (p>0.15 in each category). Among those testing positive, a greater proportion was aware of their infection in 2011 (66%) than in 2008 (56%) (p<0.001). In both years, HIV awareness was higher for older age groups, whites, and men with higher education and income. In multivariable analysis, HIV awareness increased from 2008 to 2011 overall (p<0.001) and for all age and racial/ethnic categories (p<0.01 in each category). In both years, black MSM had the highest HIV prevalence and the lowest awareness among racial/ethnic groups. These findings suggest that HIV-positive MSM are increasingly aware of their infections.

Objectives: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men., Design: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo)., Methods: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities., Results: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug., Conclusions: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Background: Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked., Objective: This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations., Methods: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies., Results: We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected., Conclusions: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.

Background: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain., Methods: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants., Results: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03)., Conclusions: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).