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Background: In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, but new infections continue to appear. The design of effective prevention strategies requires the demographic characterisation of individuals acting as sources of infection, which is the aim of this study., Methods: Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We used these sequences to identify likely transmission pairs. After demographic weighting of the recipients in these pairs to match the overall HIV-positive population, we analysed the demographic characteristics of the sources to better understand transmission in the general population., Findings: We identified a total of 300 likely transmission pairs. 178 (59·4%) were male to female, with 130 (95% CI 110-150; 43·3%) from males aged 25-40 years. Overall, men transmitted 2·09-fold (2·06-2·29) more infections per capita than women, a ratio peaking at 5·87 (2·78-15·8) in the 35-39 years source age group. 40 (26-57; 13·2%) transmissions linked individuals from different communities in the trial. Of 288 sources with recorded information on drug resistance mutations, 52 (38-69; 18·1%) carried viruses resistant to first-line ART., Interpretation: HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups, and there is no outsized contribution to new infections from importation or drug resistance mutations. Men aged 25-39 years, underserved by current treatment and prevention services, should be prioritised for HIV testing and ART., Funding: National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health., Competing Interests: Declaration of interests DJD, SHE, CF, EP-M, and OR report grant funding from NIH for this work. MSC reports other NIH grant funding. SHE reports NIH funding for meetings and travel. CF and OR report grant funding from the Bill & Melinda Gates Foundation for this work. HA reports honoraria from the Global Fund. MSC reports payments from Medscape and UpToDate for written material. WP reports consulting fees from WHO. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs., Methods: From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered., Results: Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae., Conclusions: IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms., Competing Interests: S.R.W. has received clinical trial funding from Janssen Vaccines. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A growing number of companies have announced zero-deforestation commitments (ZDCs) to eliminate commodities produced at the expense of forests from their supply chains. Translating these aspirational goals into forest conservation requires forest mapping and monitoring (M&M) systems that are technically adequate and therefore credible, salient so that they address the needs of decision makers, legitimate in that they are fair and unbiased, and scalable over space and time. We identify 12 attributes of M&M that contribute to these goals and assess how two prominent ZDC programs, the Amazon Soy Moratorium and the High Carbon Stock Approach, integrate these attributes into their M&M systems. These programs prioritize different attributes, highlighting fundamental trade-offs in M&M design. Rather than prescribe a one-size-fits-all solution, we provide policymakers and practitioners with guidance on the design of ZDC M&M systems that fit their specific use case and that may contribute to more effective implementation of ZDCs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

Background: People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention., Methods: Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention., Results: The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%)., Conclusions: Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear., Methods: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC 80 ) of acquired isolates was measured with the TZM-bl assay., Results: Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC 80 <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates., Conclusions: VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent., Methods: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months., Results: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B., Conclusions: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.)., (Copyright © 2019 Massachusetts Medical Society.)

Introduction: People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention., Methods: We present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two-arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV-positive index and their HIV-negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours., Results: The majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self-reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test - Alcohol Consumption Questions (AUDIT-C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions., Conclusions: While regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use., Methods: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants., Findings: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded., Interpretation: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered., Funding: US National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Many major corporations and countries have made commitments to purchase or produce only "sustainable" palm oil, a commodity responsible for substantial tropical forest loss. Sustainability certification is the tool most used to fulfill these procurement policies, and around 20% of global palm oil production was certified by the Roundtable on Sustainable Palm Oil (RSPO) in 2017. However, the effect of certification on deforestation in oil palm plantations remains unclear. Here, we use a comprehensive dataset of RSPO-certified and noncertified oil palm plantations (∼188,000 km 2 ) in Indonesia, the leading producer of palm oil, as well as annual remotely sensed metrics of tree cover loss and fire occurrence, to evaluate the impact of certification on deforestation and fire from 2001 to 2015. While forest loss and fire continued after RSPO certification, certified palm oil was associated with reduced deforestation. Certification lowered deforestation by 33% from a counterfactual of 9.8 to 6.6% y -1 Nevertheless, most plantations contained little residual forest when they received certification. As a result, by 2015, certified areas held less than 1% of forests remaining within Indonesian oil palm plantations. Moreover, certification had no causal impact on forest loss in peatlands or active fire detection rates. Broader adoption of certification in forested regions, strict requirements to avoid all peat, and routine monitoring of clearly defined forest cover loss in certified and RSPO member-held plantations appear necessary if the RSPO is to yield conservation and climate benefits from reductions in tropical deforestation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2017 the Author(s). Published by PNAS.)

Background: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans., Methods: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection., Results: Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions., Conclusions: The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention., Competing Interests: Conflict of interest statement: All authors have no potential conflicts of interest to declare.

Background: Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited., Methods: HIV Prevention Trials Network 058 (HPTN 058) was a randomized controlled trial designed to compare the impact of 2 medication-assisted treatment (MAT) strategies on HIV incidence or death among opioid-dependent people who inject drugs (PWID). HIV-negative opioid-dependent PWID were recruited from 4 communities in Thailand and China with historically high prevalence of HIV among PWID. A total of 1251 participants were randomly assigned to either (1) a 1-year intervention consisting of 2 opportunities for a 15-day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling [short-term medication-assisted treatment (ST-MAT)] or (2) thrice-weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions [long-term medication-assisted treatment (LT-MAT)] followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact., Results: Although the study was stopped early due to lower than expected occurrence of the primary end points, sufficient data were available to assess the impact of the interventions on drug use and injection-related risk behavior. At week 26, 22% of ST-MAT participants had negative urinalyses for opioids compared with 57% in the LT-MAT (P < 0.001). Differences disappeared in the year after treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection-related risk behaviors were significantly reduced in both groups after randomization., Conclusions: Participants receiving BUP/NX 3 times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection-related risk behavior. These data support the use of thrice-weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use.

Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (Truvada®) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research.

Background: The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. We aimed to assess these factors in a cohort of HIV-negative people at risk of infection., Methods: In our cohort study, men and transgender women who have sex with men previously enrolled in PrEP trials (ATN 082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension. We measured drug concentrations in plasma and dried blood spots in seroconverters and a random sample of seronegative participants. We assessed PrEP uptake, adherence, sexual practices, and HIV incidence. Statistical methods included Poisson models, comparison of proportions, and generalised estimating equations., Findings: We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP. Uptake was higher among those reporting condomless receptive anal intercourse (416/519 [81%] vs 809/1084 [75%], p=0·003) and having serological evidence of herpes (612/791 [77%] vs 613/812 [75%] p=0·03). Of those receiving PrEP, HIV incidence was 1·8 infections per 100 person-years, compared with 2·6 infections per 100 person-years in those who concurrently did not choose PrEP (HR 0·51, 95% CI 0·26-1·01, adjusted for sexual behaviours), and 3·9 infections per 100 person-years in the placebo group of the previous randomised phase (HR 0·49, 95% CI 0·31-0·77). Among those receiving PrEP, HIV incidence was 4·7 infections per 100 person-years if drug was not detected in dried blood spots, 2·3 infections per 100 person-years if drug concentrations suggested use of fewer than two tablets per week, 0·6 per 100 person-years for use of two to three tablets per week, and 0·0 per 100 person-years for use of four or more tablets per week (p<0·0001). PrEP drug concentrations were higher among people of older age, with more schooling, who reported non-condom receptive anal intercourse, who had more sexual partners, and who had a history of syphilis or herpes., Interpretation: PrEP uptake was high when made available free of charge by experienced providers. The effect of PrEP is increased by greater uptake and adherence during periods of higher risk. Drug concentrations in dried blood spots are strongly correlated with protective benefit., Funding: US National Institutes of Health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons., Design and Methods: The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy., Results: There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy., Conclusions: In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

Epidemic modeling suggests that a major scale-up in HIV treatment could have a dramatic impact on HIV incidence. This has led both researchers and policymakers to set a goal of an "AIDS-Free Generation." One of the greatest obstacles to achieving this objective is the number of people with undiagnosed HIV infection. Despite recent innovations, new research strategies are needed to identify, engage, and successfully treat people who are unaware of their infection.

Objective: To review the evidence for antiretroviral 'treatment as prevention' for HIV transmission among MSM., Methods: We reviewed studies that assess the biological plausibility that virally suppressive antiretroviral therapy (ART) reduces HIV infectiousness via anal intercourse and the epidemiologic evidence of whether ART has played a role in attenuating HIV incidence among MSM., Results: Although ART treatment among MSM is likely to provide some preventive benefit, it is unknown whether it will reduce HIV infectiousness via anal intercourse to the same extent as via penile-vaginal intercourse. Additional research is needed on the pharmacokinetic properties of specific antiretroviral agents in the gastrointestinal tract. Estimates of risk behaviors and the incidence of HIV among MSM before and after the introduction and expansion of ART suggest that the population-level protective benefits of ART may be attenuated by a number of factors, most notably, continuing or increasing frequency of condomless anal intercourse and incidence of other sexually transmitted infections (STIs). Additional studies are needed on the impact of ART on HIV sexual risk behaviors and transmission among MSM outside of developed countries in North America, western Europe, and Australia., Conclusion: The benefits of treatment as prevention for MSM are highly plausible, but not certain. In the face of these unknowns, treatment guidelines for earlier ART initiation should be considered within a combination prevention strategy that includes earlier diagnosis, expanded STI treatment, and structural and behavioral interventions.

Reliable methods for measuring human immunodeficiency virus (HIV) incidence are a high priority for HIV prevention. They are particularly important to assess the population-level effectiveness of new prevention strategies, to evaluate the community-wide impact of ongoing prevention programs, and to assess whether a proposed prevention trial can be performed in a timely and cost-efficient manner in a particular population and setting. New incidence assays and algorithms that are accurate, rapid, cost-efficient, and can be performed on easily-obtained specimens are urgently needed. On May 4, 2011, the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), sponsored a 1-day workshop to examine strategies for developing new assays to distinguish recent from chronic HIV infections. Participants included leading investigators, clinicians, public health experts, industry, regulatory specialists, and other stakeholders. Immune-based parameters, markers of viral sequence diversity, and other biomarkers such as telomere length were evaluated. Emerging nanotechnology and chip-based diagnostics, including algorithms for performing diverse assays on a single platform, were also reviewed. This report summarizes the presentations, panel discussions, and the consensus reached for pursuing the development of a new generation of HIV incidence assays.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition., Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections., Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57)., Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).

Research on the prevention of human immunodeficiency virus (HIV)-1 infection is at a critical juncture. Major methodological challenges to performing prevention trials have emerged, and one after another promising biomedical interventions have failed to reduce the incidence of HIV-1 infection. Nevertheless, there is growing optimism that progress can be achieved in the near term. Mathematical modeling indicates that 2 new strategies, "test and treat" and preexposure prophylaxis, could have a major impact on the incidence of HIV-1 infection. Will our hopes be justified? We review the potential strengths and limitations of these antiretroviral "treatment as prevention" strategies and outline other new options for reducing the incidence of HIV-1 infection in the near term. By maximizing the potential of existing interventions, developing other effective strategies, and combining them in an optimal manner, we have the opportunity to bring the HIV-1 epidemic under control.

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.

Objective: To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus., Design: A prospective analysis of 55 HIV-1-infected women., Methods: Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load., Results: Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03)., Conclusion: HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

Background: The level of serum albumin is associated with mortality in a wide variety of chronic diseases. However, few studies have examined the relationship between serum albumin and survival in HIV-1 infection., Objectives: To determine whether the serum albumin level is associated with survival in HIV-1 infected women., Design: Prospective cohort study. Patients were interviewed and examined at 6 month intervals., Setting: A North American multi-institutional cohort of HIV-infected women from five geographical areas., Participants: A total of 2056 HIV-infected women at various stages of disease., Measurements: Mortality during the first 3 years of follow-up. The relative risk of death by serum albumin level was estimated using a proportional hazards ratio adjusted for CD4 cell count, HIV-1-RNA level and other relevant covariates., Result: Three year mortality for women in the lowest serum albumin category (< 35 g/l) was 48% compared with 11% in the highest category (> or = 42 g/l; P < 0.001). The adjusted relative hazard (RH) of death was 3.1 times greater for those in the lowest albumin category (P < 0.01). The excess risk associated with lower serum albumin levels remained when subjects with moderate to severe immunosuppression and abnormal kidney and liver function were excluded (P < 0.01)., Conclusion: The baseline serum albumin level is an independent predictor of mortality in HIV-1-infected women. The serum albumin level may be a useful additional marker of HIV-1 disease progression, particularly among asymptomatic women with little or no evidence of immunosuppression.

Trends in the vertical transmission rate of HIV and evolving antiretroviral usage between 1990 and 1998 within the Women and Infants Transmission Study were evaluated. A decline in mother-infant transmission was temporally associated with advances in therapy, especially when regimens including a protease inhibitor were included in the analysis.

Hepatitis C virus infection, which is far more prevalent than human immunodeficiency virus (HIV)-1, can lead to cirrhosis, hepatocellular carcinoma, hepatic failure, and death. Like HIV-1, hepatitis C is transmitted parenterally, sexually, and from mother to infant. The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) recently recommended that all children born to women who are infected with hepatitis C virus or have risk factors for infection be screened for hepatitis C. Most infected women are asymptomatic and unaware of their infection, so routine prenatal testing is needed to fully meet that goal. We do not believe that current data justify universal testing, but we believe it is time for all obstetricians to test selectively based on risk factors.

Vitamin A levels in plasma and other nutritional indices were measured during pregnancy for 449 women enrolled in a multicenter cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). During the third trimester, 29.6% of the women had low (20 to <30 microg/dL) and 11.1% had very low (<20 microg/dL) vitamin A levels. Vitamin A and body mass index, serum albumin levels, and hemoglobin levels were weakly correlated. After adjustment for other covariates, women with low and very low vitamin A levels before the third trimester were more likely to deliver infants with low birth weight (<2500 g) than were those with higher levels (odds ratio [OR], 4.58; 95% confidence interval [CI], 1.57-13.4; and OR, 6.99; 95% CI, 1.09-45.0, respectively). However, there was no statistically significant association between vitamin A level and mother-to-infant transmission of HIV-1. Anemia and low body mass index before the third trimester were associated with an increased risk of transmission in univariate analyses but not in multivariate analyses.

Changes in CD4 + cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2Ralpha), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levels began to rise well before delivery and were in decline by 2 months postpartum. sIL-2Ralpha and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2Ralpha was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whites than non-whites and in 'hard' drug users than non-users (P < or = 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P < or = 0.001 for each) but not sIL-2Ralpha (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes.

Objective: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum., Study Design: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time., Results: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65)., Conclusion: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4+ lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1). Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-1 transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

We evaluated the relationship between immunologic status and vaginal colonization or infection with Candida albicans for 605 women enrolled in a multicenter, prospective cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). A low CD4+ lymphocyte level (< 14% vs. > or = 14%, which corresponds to an absolute count of approximately 200 x 10(6)/L) was associated with a two- to fivefold increased likelihood of vaginal colonization (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.19) and vaginal candidiasis (OR, 3.08; 95% CI, 1.21-7.71) during pregnancy and during the postpartum period (OR, 2.98; 95% CI, 1.51-5.88 and OR, 5.45; 95% CI, 1.73-16.6, respectively). These associations persisted in multivariate logistic regression analyses. No associations with CD8+ lymphocyte levels or CD8+ CD38+ or other lymphocyte subset levels were found after adjustment for CD4+ cell level and other covariates. However, postpartum (but not antepartum) antibiotic use and pregnancy were also associated with vaginal colonization and candidiasis (P < or = .001 for each). Vaginal candidiasis was not associated with an increased risk of mother-to-infant transmission of HIV-1; however, a related, more inclusive variable, clinical vaginitis or vaginosis of any etiology at the last antepartum visit, was associated with mother-to-infant transmission (OR, 1.92; 95% CI, 1.07-3.43). These findings emphasize the complex, multifactorial nature of vaginal candidiasis and highlight the need for safe and effective treatment and prevention strategies for women with advanced HIV infection.

Cigarette smoking has been associated with impaired immune defenses and an increased risk of certain infectious and neoplastic diseases in HIV-1 seronegative populations. We examined the relationship between cigarette smoking and clinical outcome in a prospective cohort of 3221 HIV-1-seropositive men and women enrolled in the Terry Beirn Community Programs for Clinical Research on AIDS. Differences in clinical outcomes between never, former, and current cigarette smokers were assessed using proportional hazards regression analysis. After adjustment for CD4+ cell count, prior disease progression, use of antiretroviral therapy, and other covariates, there was no difference between current smokers and never smokers in the overall risk of opportunistic diseases [relative hazard (RH) = 1.05; 95% confidence interval (CI) 0.90-1.23; p = 0.52] or death (RH = 1.00; 95% CI 0.86-1.18; p = 0.97). However, current smokers were more likely than never smokers to develop bacterial pneumonia (RH = 1.57; 95% CI 1.14-2.15; p = 0.006), oral candidiasis (RH = 1.37; 95% CI 1.16-1.62; p = 0.0002), and AIDS dementia complex (RH = 1.80; 95% CI 1.11-2.90; p = 0.02). In addition, current smokers were less likely to develop Kaposi's sarcoma (RH = 0.58; 95% CI 0.39-0.88; p = 0.01) and several other non-respiratory tract diseases. If confirmed by other studies, these findings have important clinical implications.

Objective: Our objective was to examine changes in CD4+ and CD8+ cell levels during pregnancy and post partum and to determine whether they differ for human immunodeficiency virus-1-seropositive and seronegative women., Study Design: A total of 192 human immunodeficiency virus-1-seropositive and 148 seronegative women enrolled in a study of mother-to-child transmission of human immunodeficiency virus-1 who had at least two lymphocyte subset measurements performed during pregnancy or post partum were included in this analysis. Mixed effects repeated-measures models were developed to examine changes in CD4+ and CD8+ cell levels during this period., Results: Consistent with prior reports that CD4+ cell levels decline during pregnancy and return to normal post partum, percent levels increased between the third trimester and 12 months post partum among human immunodeficiency virus-seronegative women (1.98%, p = 0.04). However, CD4+ levels declined steadily during pregnancy and post partum among seropositive women (-1.57%, p = 0.02 between the third trimester and 12 months post partum; =2.65%, p = 0.0004 between 2 and 24 months post partum). The percent CD8+ cell levels increased at or near delivery and declined to baseline between 2 and 6 months post partum in both seronegative and seropositive women, although only the declines were statistically significant in both groups (-2.66%, p = 0.004; and -2.02%, p = 0.02, respectively)., Conclusions: The percent CD4+ cell levels declined steadily during pregnancy and post partum among human immunodeficiency virus-seropositive women, indicating that human immunodeficiency virus disease continues to progress during this period. The percent CD8+ cell levels increased at or near delivery and declined to baseline post partum in both seronegative and seropositive women. These findings may have important clinical implications for both human immunodeficiency virus-infected and uninfected pregnant women.

Objective: Intrapartum events may play a role in determining the likelihood of vertical transmission of human immunodeficiency virus-1. Timing and duration of rupture of membranes have been shown to modify transmission risk of other organisms but have not been examined for human immunodeficiency virus. This study was undertaken to assess the relationship between duration of rupture of membranes, maternal immune status, and transmission of human immunodeficiency virus., Methods: The Mothers' and Infants' Cohort Study enrolled 207 human immunodeficiency virus-positive women and their infants at five study sites in Brooklyn and the Bronx, New York between January 1986 and January 1991. One hundred twenty-seven woman-infant sets for whom antepartum CD4+ levels were available, the infant's human immunodeficiency virus infection outcome was known, and the duration of ruptured membranes could be determined were included in this analysis., Results: Thirty of the 127 evaluable infants (24%) were infected. Women with low CD4+ levels (< 20%) were significantly more likely to transmit the virus if rupture of membranes was > or = 4 hours (relative risk 4.53, 95% confidence interval 1.14 to 1.81, p = 0.02). The same association was not observed among women with higher CD4+ levels (relative risk 1.11, 95% confidence interval 0.52 to 2.69, p = 0.69). No association with the duration of labor or mode of delivery was seen., Conclusions: In this urban North American cohort women with low CD4+ levels were significantly more likely to transmit human immunodeficiency virus to their offspring if the duration of rupture of membranes was > or = 4 hours.

To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Between August 1989 and January 1990, 16 patients on an alcoholism rehabilitation ward (ARW) developed positive sputum cultures for Mycobacterium fortuitum. During a 2-wk surveillance period, six of 43 ARW patients but none of 20 staff members had positive sputum cultures. In addition, none of 54 patients and staff on an adjacent ward sharing the same ice machine and water supply had positive cultures, and none of 92 acid-fast bacilli cultures performed on all sputum specimens from all other inpatient sources during the same 2-wk period were positive. The only exposure factor common to all cases was the use of one or both of the ward showers. Compared with 36 ARW control patients, cases were more likely to report clinical criteria for chronic bronchitis (odds ratio, 6.6; 95% confidence interval, 1.5 to 28.6; p = 0.02). Using phenotype analysis, plasmid profiles, and pulsed-field gel electrophoresis of large genomic DNA restriction enzyme fragments, the 16 case isolates were found to be identical. This strain of M. fortuitum was also cultured from a tap connected to the water line supplying the ARW showers, but not from the showers themselves. No further cases were identified after the showers were disconnected and decontaminated. To our knowledge, this is the first clinical use of pulsed-field gel electrophoresis for genetic comparison of mycobacterial strains. It demonstrates the important potential of this technique for studying the epidemiology of mycobacterial infections. Showers should be considered a possible source of nosocomial respiratory tract colonization with M. fortuitum.

A definitive conclusion regarding the potential for the presence of neutralizing antibody to epitopes of the V3 loop to attenuate or prevent vertical transmission of HIV infection cannot be made based on the results of these four studies. However, the studies provide an intriguing suggestion that it may be possible to identify an epitope or array of epitopes from the V3 loop of judiciously selected HIV isolates that could induce protective immunity against HIV. Future collaborative studies are needed to standardize and independently validate the various assays. A recent conference, Early Diagnosis of HIV Infection in Infants, sponsored by the National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases and the Centers for Disease Control, provided a forum to facilitate exchange of information among researchers in this field, and encourage future collaborative efforts. If one or more subpopulations of anti-gp120/V3 loop or other neutralizing antibodies are indeed associated with a decreased risk of maternal-infant transmission, it becomes important to determine whether these antibodies are protective per se or are merely surrogate markers of a different mechanism. The former conclusion seems to be supported by the finding of HIV-specific antibodies in seropositive persons' saliva and breast milk, both of which have relatively low infectivity, although the potential neutralizing activities of these antibodies have not been adequately evaluated. The development and testing of a highly specific (monoclonal antibody-derived) passive immunotherapy will probably be required to answer this question.(ABSTRACT TRUNCATED AT 250 WORDS)

Two hundred and two homosexual men enrolled in a prospective cohort study of AIDS risk were assessed for differences in the occurrence and progression of human immunodeficiency virus type 1 (HIV-1) infection with respect to cigarette smoking. Among subjects who were initially seronegative, smokers were more likely than nonsmokers to become HIV-1 seropositive (p = 0.03). After seroconversion, serum beta 2-microglobulin and CD4+ lymphocyte levels were elevated in cigarette smokers relative to nonsmokers (p = 0.02 for both comparisons), but both of these differences disappeared within 2 years. There was no detectable difference in the risk of AIDS or Pneumocystis carinii pneumonia with respect to smoking. Our data suggest that cigarette smoking may alter the immune response to HIV-1 infection, but it appears to have no marked effect on clinical outcome. They also suggest that cigarette smoking may be a surrogate marker for continued high-risk sexual behavior in homosexual men.

We report a case of disseminated Mycobacterium fortuitum in a 76-yr-old male with no identifiable predisposing factors except chronic interstitial lung disease. Recurrent, progressive pulmonary symptoms and radiographic findings were followed by the development of multiple, culture-positive peripheral lesions. The patient responded rapidly and completely to combination therapy consisting primarily of ciprofloxacin, minocycline, and surgical drainage. Our experience supports the cautious use and further study of fluorinated quinolones for M. fortuitum infections caused by susceptible isolates.