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We evaluated the accuracy of heat-denatured, amplification-boosted ultrasensitive p24 assay (Up24) compared with reverse transcriptase polymerase chain reaction (RT-PCR). We tested 394 samples from Ugandans infected with HIV-1 non-B subtypes. We compared Up24 levels (HIV-1 p24 Core Profile enzyme-linked immunosorbent assay (ELISA), NEN Life Science Products) to RNA viral loads (Amplicor HIV-1 Monitor 1.5, Roche) by linear regression, and calculated sensitivity, specificity, positive and negative predictive values. Median viral load was 4.9 log10 copies/mL (interquartile range [IQR], 2.6-5.5); 114 samples (29%) were undetectable (<400 copies/mL). Sensitivity of the Up24 assay to detect viral load ⩾400 copies/mL was 69%, specificity was 67%, and positive and negative predictive values were 84% and 47%, respectively. Sensitivity of Up24 was 90%, 80%, 68%, 62% and 45% to detect viral loads of >500,000, 250,000-500,000, 100,000-250,000, 50,000-100,000 and 400-50,000 copies/mL, respectively. In conclusion, when compared with RT-PCR for patients infected with non-B subtypes, the Up24 demonstrated limited sensitivity especially at low viral loads. Moreover, the Up24 was positive in 33% of samples deemed undetectable by RT-PCR, which may limit the use of the Up24 to detect viral suppression. [ABSTRACT FROM AUTHOR]

Unlabelled: In Rakai, Uganda, human immunodeficiency virus (HIV)-positive men were randomized to undergo either immediate circumcision (intervention arm) or delayed circumcision (control arm). Penile swab samples were assayed for high-risk human papillomavirus (HR-HPV) by Roche HPV Linear Array at enrollment and at 24 months (intervention arm, 103 subjects; control arm, 107 subjects). Rate ratios (RRs) of HR-HPV were estimated by Poisson regression. At 24 months, HR-HPV prevalence was found in 57 (55.3%) of 103 subjects in the intervention arm and in 77 (71.7%) of 107 subjects in the control arm (RR, 0.77; 95% confidence interval [CI], 0.62-0.97). Multiple HR-HPV infections were found in 19 (22.4%) of 85 subjects in the intervention arm and in 45 (42.5%) of 106 subjects in the control arm (RR, 0.53; 95% CI, 0.33-0.83). New HR-HPV genotypes were acquired by 34 (42.0%) of 81 subjects in the intervention arm and by 53 (57.0%) 85 subjects in the control arm (RR, 0.74; 95% CI, 0.54-1.01; P = .06). Multiple new HR-HPV genotypes were acquired by 8 (9.9%) of 81 subjects in the intervention arm and by 23 (24.7%) of 93 subjects in the control arm (RR, 0.40; 95% CI, 0.19-0.84; P = .01). Circumcision did not affect the acquisition of single HR-HPV infections (RR, 1.00; 95% CI 0.65-1.53) or clearance of HR-HPV infections (RR, 1.09; 95% CI 0.94-1.27). Circumcision of HIV-positive men reduced the prevalence and incidence of multiple HR-HPV infections.Trial Registration: ClinicalTrials.gov identifier: NCT00124878 . [ABSTRACT FROM AUTHOR]

Background: Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+) T cells, potentially complicating future treatment.Methods: Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4(+) T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance.Results: Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women.Conclusions: A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. [ABSTRACT FROM AUTHOR]

Objective: To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site.Methods: Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology.Results: Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85).Conclusions: STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting. [ABSTRACT FROM AUTHOR]

A cross-sectional survey was conducted to determine the sociodemographic correlates of herpes simplex virus type 2 (HSV-2) infection among male and female commercial sex workers in Kunming, Yunnan Province of China. HSV-2 prevalence was 33.0%, human immunodeficiency virus (HIV) infection was 2.4% and hepatitis C virus (HCV) infection was 6.8%. Subjects who were positive for HSV-2 had a significantly higher prevalence of HIV infection (5.5% versus 0.9%, P = 0.002; odds ratio [OR]: 6.4, P = 0.006) and HCV infection (18.7% versus 2.4%, P < 0.001; OR: 7.6, P < 0.001) compared with HSV-2-negative individuals. Risk factors that increased the odds of HSV-2 infection were HIV infection, HCV infection, being female, and having a steady sex partner within the last six months (P ⩽ 0.01). In a multivariate analysis, being female (OR: 6.6, P < 0.001), having HCV infection (OR: 5.9, P < 0.001) and having a sex partner within the last six months (OR: 2.2, P < 0.05) showed greater odds of being infected with HSV-2. A strong relationship was found between HSV-2, HIV and HCV infections. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. METHODS: We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4(+) cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4(+) cell count of < or =250 cells/mm(3)) and to AIDS-associated death. RESULTS: A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years; P = .022). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71-11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. CONCLUSIONS: HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Context: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood.Objective: To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use.Design and Setting: Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years.Subjects: A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up.Main Outcome Measures: Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death.Results: Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis.Conclusions: Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456 [ABSTRACT FROM AUTHOR]

To test the hypothesis that person-to-person variability in blood levels of hepatitis C virus (HCV) RNA can be explained, the quantity of HCV RNA was assessed in 969 persons who acquired HCV infection in the context of injection drug use. Serum HCV RNA levels ranged from 200,000 to >120 million equivalents/mL (the linear range of the assay). The median log10 HCV RNA level was 0.46 higher in 468 human immunodeficiency virus (HIV)-positive persons than in 501 HIV-negative persons (P<.001). In addition, among HIV-negative persons, lower HCV RNA levels were independently associated with younger age (P<.001), ongoing hepatitis B infection (P=.005), and the absence of needle sharing (P=.02). However, >90% of the person-to-person HCV RNA level variability was not explained by these sociodemographic, environmental, and virologic factors. Additional research is necessary to ascertain what determines the level of HCV RNA in blood. [ABSTRACT FROM AUTHOR]

The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ⩾ six months and 147 from ART-naïve patients. The Roche assay detected ⩾400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ⩾400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ⩾400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ⩾400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ⩾400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P< 0.0001; mean difference, 0.05). The limits of agreement were 20.97 and 1.07 log10 copies/mL (mean±2 SD). The Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 2 (HSV-2) infection is one of the most common sexually transmitted infections (STIs) worldwide. While glycoprotein G-2 enzyme-linked immunosorbent assays are commonly used for the serological detection of HSV-2 antibodies, they have low specificity in developing countries. The Euroline Western blot (WB) is a commercially available assay that is easy to perform; however, little is known about its performance characteristics. This study evaluated Euroline WB for the detection of HSV-2 antibodies compared with University of Washington Western blot in three geographically different regions: Baltimore, MD, USA; Rakai, Uganda; and Kunming, China. Among the 135 American men attending a STI clinic in Baltimore, MD, 72% (n = 97) were HSV-2-positive by Euroline WB, showing a sensitivity of 97.8% and a specificity of 81.8%. Among the 273 commercial sex workers in Kunming, 62.3% were HSV-2-positive by Euroline WB (sensitivity 96.9%, specificity 89.1%). Among the 437 Ugandans in Rakai, 67.3% were HSV-2-positive by Euroline WB (sensitivity 98.7%, specificity 65.4%). The Euroline WB has a consistently high sensitivity, but specificity varied significantly among the different locations. [ABSTRACT FROM AUTHOR]

HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and selfreported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection. Methods V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing. Results Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR. Conclusion CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.

Abstract Background Project Accept is a community randomized, controlled trial to evaluate the efficacy of community mobilization, mobile testing, same-day results, and post-test support for the prevention of HIV infection in Thailand, Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV rapid testing and determined HIV prevalence in the Project Accept pilot study. Methods Two HIV rapid tests were performed in parallel in local laboratories. If the first two rapid tests were discordant (one reactive, one non-reactive), a third HIV rapid test or enzyme immunoassay was performed. Samples were designated HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests were discordant, and HIV POS if the first two tests were reactive. Samples were re-analyzed in the United States using a panel of laboratory tests. Results HIV infection status was correctly determined based on-in country testing for 2,236 (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV-positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV DISC samples were incorrectly identified as HIV-positive based on the in-country tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe 14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall prevalence: 14.4%). Conclusions In-country testing based on two HIV rapid tests correctly identified the HIV infection status for 99.5% of study participants; most participants with discordant HIV rapid tests were not infected. HIV prevalence varied considerably across the study sites (range: 0.6% to 24.4%). Trial Registration ClinicalTrials.gov registry number NCT00203749.

Abstract Objective To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens. Methods Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. Results The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. Conclusion Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients.

Abstract Background The objective of this study was to estimate the effect of male circumcision (MC) on HIV acquisition estimated using HIV incidence assays and to compare it to the effect measured by survival analysis. Methods We used samples collected during the MC randomized controlled trial (ANRS-1265) conducted in Orange Farm (South Africa) among men aged 18 to 24. Among the 2946 samples collected at the last follow-up visit, 194 HIV-positive samples were tested using two incidence assays: Calypte HIV-EIA (BED) and an avidity assay based on the BioRad HIV1/2+O EIA (AI). The results of the assays were also combined (BED-AI). The samples included the 124 participants (4.2% of total) who were HIV-positive at randomization. The protective effect was calculated as one minus the intention-to-treat incidence rate ratio in an uncorrected manner and with correction for misclassifications, with simple theoretical formulae. Theoretical calculations showed that the uncorrected intention-to-treat effect was approximately independent of the value of the incidence assay window period and was the ratio of the number tested recent seroconverters divided by the number tested HIV-negative between the randomization groups. We used cut-off values ranging from 0.325 to 2.27 for BED, 31.6 to 96 for AI and 0.325-31.6 to 1.89-96 for BED-AI. Effects were corrected for long-term specificity using a previously published formula. 95% Confidence intervals (CI) were estimated by bootstrap resampling. Results With the highest cut-off values, the uncorrected protective effects evaluated by BED, AI and BED-AI were 50% (95%CI: 27% to 66%), 50% (21% to 69%) and 63% (36% to 81%). The corrections for misclassifications were lower than 50% of the number of tested recent. The corrected effects were 53% (30% to 70%), 55% (25% to 77%) and 67% (38% to 86%), slightly higher than the corresponding uncorrected values. These values were consistent with the previously reported protective effect of 60% (34% to 76%) obtained with survival analysis. Conclusions HIV incidence assays may be employed to assess the effect of interventions using cross-sectional data.

Background: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined.Methods: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors.Results: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94).Conclusions: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.). [ABSTRACT FROM AUTHOR]

Background: Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men.Methods: 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984.Findings: Baseline characteristics of the men in the intervention and control groups were much the same at enrollment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up.Interpretation: Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men. [ABSTRACT FROM AUTHOR]