Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded ß-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.

Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.

Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.

Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors.

V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B.9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies.

Prevalence of sexually transmitted infections among pregnant women with known HIV status in northern Tanzania.

OBJECTIVES: To determine the prevalence of sexually transmitted infections (STIs) and other reproductive tract infections (RTIs) among pregnant women in Moshi, Tanzania and to compare the occurrence of STIs/RTIs among human immunodeficiency virus (HIV)-infected and uninfected women. METHODS: Pregnant women in their 3rd trimester (N = 2654) were recruited from two primary health care clinics between June 2002 and March 2004. They were interviewed, examined and genital and blood samples were collected for diagnosis of STIs/RTIs and HIV. RESULTS: The prevalence of HIV, active syphilis and herpes simplex virus - type 2 (HSV-2) were 6.9%, 0.9% and 33.6%, respectively, while 0.5% were positive for N gonorrhoeae, 5.0% for T vaginalis and 20.9% for bacterial vaginosis. Genital tract infections were more prevalent in HIV-seropositive than seronegative women, statistically significant for syphilis (3.3% vs 0.7%), HSV-2 (43.2% vs 32.0%), genital ulcers (4.4% vs 1.4%) and bacterial vaginosis (37.2% vs 19.6%). In comparison with published data, a declining trend for curable STIs/RTIs (syphilis, trichomoniasis and bacterial vaginosis) was noted. CONCLUSION: Rates of STIs and RTIs are still high among pregnant women in Moshi. Where resources allow, routine screening and treatment of STIs/RTIs in the antenatal care setting should be offered. Higher STIs/RTIs in HIV-seropositive women supports the expansion of HIV-counseling and testing services to all centers offering antenatal care. After identification, STIs/RTIs need to be aggressively addressed in HIV-seropositive women, both at antenatal and antiretroviral therapy care clinics.

High prevalence of Entamoeba moshkovskii in a Tanzanian HIV population.

Entamoeba moshkovskii and Entamoeba dispar are microscopically indistinguishable from the pathogenic species Entamoeba histolytica. There are limited data on the prevalence of these commensal infections from Africa. We utilized PCR and antigen detection to evaluate the carriage rate of E. moshkovskii, E. dispar, and E. histolytica infection in stool from a cohort of HIV-suspected or confirmed inpatients from Tanzania. E. histolytica was detected by ELISA in 4% (5/118) while E. moshkovskii and E. dispar were detected by PCR in 13% (18/136) and 5% (7/136) of individuals, respectively (P<0.05). Supporting their commensal nature, neither E. moshkovskii nor E. dispar infection was statistically associated with HIV status, CD4 count, or the presence of diarrhea. These data suggest E. moshkovskii is a common infection in HIV-infected individuals in northern Tanzania and supports the concept that the microscopic detection of Entamoeba should be interpreted cautiously.

The role of in-migrants in the increasing rural HIV-1 epidemic: results from a village population survey in the Kilimanjaro region of Tanzania.

OBJECTIVE: To investigate the magnitude of rural in-migration and the role of in-migrants in the observed increase in HIV-1 prevalence in rural Kilimanjaro, Tanzania. METHODS: A cross-sectional study involving the adult population aged 15-44 years residing in a rural village was conducted from March to May of 2005. Participants were interviewed regarding their risk behaviors and gave blood for HIV-1 and syphilis testing. RESULTS: Overall, the response rate was 73.0% (1528/2093). A total of 699 (48.1%) participants reported having in-migrated to the village at some point during their life. The prevalences of HIV-1 infection were 1.8%, 2.3%, and 3.7% among non-in-migrant, long-term in-migrant, and recent in-migrant men, respectively (p(trend)<0.001). The corresponding prevalences among women were 9.2%, 11.5%, and 14.5%, respectively (p(trend)=0.048). The odds of HIV-1 infection were higher among recent in-migrants as compared to non-in-migrants (men: adjusted odds ratio (AOR) 2.4, 95% CI 1.8-6.6; women: AOR 2.3, 95% CI 1.1-5.0). Risk behaviors were inversely related to years since in-migration for both sexes. CONCLUSIONS: The results suggest that rural in-migration is common for both men and women. In-migrants were at higher risk for HIV-1 infection and contributed significantly to increased rural HIV-1 prevalence. More studies to examine the rate and broader causes of rural in-migration in similar communities are called for. These may help in the design of intervention strategies for curbing the rising rural HIV epidemic.

Predicting CD4 lymphocyte count <200 cells/mm(3) in an HIV type 1-infected African population.

Clinical criteria are recommended to select HIV-infected patients for initiation of antiretroviral therapy when CD4 lymphocyte testing is unavailable. We evaluated the performance characteristics of WHO staging criteria, anthropometrics, and simple laboratory measurements for predicting CD4 lymphocyte count (CD4 count) <200 cells/mm(3) among HIV-infected patients in Tanzania. A total of 202 adults, diagnosed with HIV infection through community-based testing, underwent a detailed evaluation including staging history and examination, anthropometry, complete blood count, erythrocyte sedimentation rate (ESR), and CD4 count. Univariable analysis and recursive partitioning were used to identify characteristics associated with CD4 count 200 cells/mm(3). Of 202 participants 109 (54%) had a CD4 count <200 cells/mm(3). Characteristics most strongly associated with CD4 count <200 cells/mm(3) (p-value <0.0001) were the presence of mucocutaneous manifestations (72% vs. 28%), lower total lymphocyte count (TLC) (median 1,450 vs. 2,200 cells/mm(3)), lower total white blood cell count (median 4,200 vs. 5,500 cells/mm(3)), and higher ESR (median 95 vs. 53 mm/h). In a partition tree model, TLC <1,200 cells/mm(3), ESR >or=120 mm/h, or the presence of mucocutaneous manifestations yielded a sensitivity of 0.85 and specificity of 0.63 for predicting CD4 count <200 cells/mm(3). The sensitivity of the 2006 WHO Staging system improved from 0.75 to 0.93 with inclusion of these parameters, at the expense of specificity (0.36 to 0.26). The presence of mucocutaneous manifestations, TLC <1,200 cells/mm(3), or ESR >or=120 mm/h was a strong predictor of CD4 count <200 cells/mm(3) and enhanced the sensitivity of the 2006 WHO staging criteria for identifying patients likely to benefit from antiretrovirals.

Trends in HIV-1 prevalence and risk behaviours over 15 years in a rural population in Kilimanjaro region of Tanzania.

BACKGROUND: Monitoring dynamics in HIV-1 infection and risk behaviours is important in evaluating, adjusting and scaling up prevention programmes. The objective of this study was to estimate trends in the prevalence of HIV-1 infection and risk behaviours over 15 years in a rural village population in Kilimanjaro region of Tanzania using repeated population-based cross-sectional surveys. METHODS: Four rounds of HIV-1 sero-epidemiological and behavioural surveys were completed during 1991 to 2005 in the study village. House-to-house registrations of people aged 15-44 years with an address in the village were conducted before each survey. All consenting individuals were then interviewed for pertinent risk behaviours and tested for HIV-1 seropositivity. RESULTS: Participation proportions ranged from 73.0% to 79.1%. Overall, age and sex-adjusted HIV-1 prevalence increased from 3.2% in 1991 to 5.6 % in 2005 (relative increase 75.0%; ptrend < 0.001). The increase was significant for both men and women (ptrends < 0.001) and more evident among women aged 35-44 years (2.0% to 13.0%, ptrend < 0.001). Among participants aged 15-24 years a decrease in number of sexual partners was observed with a corresponding stable HIV-1 prevalence. Participants aged 25-44 years continued to report multiple sexual partners, and this was corroborated with increased HIV-1 prevalence trend (4.0% to 9.0%, ptrends < 0.001). Among men aged 25-44 years and women aged 15-24 years significant increases in condom use were observed (ptrend < 0.01). CONCLUSION: The HIV-1 prevalence seems to have increased among older participants but remained stable among younger participants. Encouraging trends toward safer sex practices were observed among young participants, while only modest behavioural changes were seen among the older participants. Prevention efforts in rural areas need to be intensified and to address people of all ages.

Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of Tanzania: implications for prevention and treatment.

BACKGROUND: Variability in stages of the HIV-1 epidemic and hence HIV-1 prevalence exists in different areas in sub-Saharan Africa. The purpose of this study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk factors that may help to develop preventive strategies in rural Kilimanjaro, Tanzania. METHODS: A cross-sectional study was conducted between March and May of 2005 involving all individuals aged between 15-44 years having an address in Oria Village. All eligible individuals were registered and invited to participate. Participants were interviewed regarding their demographic characteristics, sexual behaviors, and medical history. Following a pre-test counseling, participants were offered an HIV test. RESULTS: Of the 2 093 eligible individuals, 1 528 (73.0%) participated. The overall age and sex adjusted HIV-1 prevalence was 5.6%. Women had 2.5 times higher prevalence (8.0% vs. 3.2%) as compared to men. The age group 25-44 years, marriage, separation and low education were associated with higher risk of HIV-1 infection for both sexes. HIV-1 infection was significantly associated with >2 sexual partners in the past 12 months (women: Adjusted odds ratio [AOR], 2.5 (95%CI: 1.3-4.7), and past 5 years, [(men: AOR, 2.2 (95%CI:1.2-5.6); women: AOR, 2.5 (95%CI: 1.4-4.0)], unprotected casual sex (men: AOR,1.8 95%CI: 1.2-5.8), bottled alcohol (Men: AOR, 5.9 (95%CI:1.7-20.1) and local brew (men: AOR, 3.7 (95%CI: 1.5-9.2). Other factors included treatment for genital ulcers and genital discharge in the past 1 month. Health-related complaints were more common among HIV-1 seropositive as compared to seronegative participants and predicted the presence of HIV-1 infection. CONCLUSION: HIV-1 infection was highly prevalent in this population. As compared to our previous findings, a shift of the epidemic from a younger to an older age group and from educated to uneducated individuals was observed. Women and married or separated individuals remained at higher risk of infection. To prevent further escalation of the HIV epidemic, efforts to scale up HIV prevention programmes addressing females, people with low education, lower age at marriage, alcohol consumption, condom use and multiple sexual partners for all age groups remains a top priority. Care and treatment are urgently needed for those infected in rural areas.

HIV among pregnant women in Moshi Tanzania: the role of sexual behavior, male partner characteristics and sexually transmitted infections.

BACKGROUND: Women continue to be disproportionately affected by HIV in Tanzania, and factors contributing to this situation need to be identified. The objective of this study was to determine social, behavioral and biological risk factors of HIV infection among pregnant women in Moshi urban, Tanzania. In 2002-2004, consenting women (N = 2654), attending primary health clinics for routine antenatal care were interviewed, examined and biological samples collected for diagnosis of HIV and other sexually transmitted/reproductive tract infections. RESULTS: The prevalence of HIV was 6.9%. The risk for HIV was greater among women whose male partner; had other sexual partners (adjusted odds ratio [AOR], 15.11; 95% confidence interval [CI], 8.39-27.20), traveled frequently (AOR, 1.79; 95% CI, 1.22-2.65) or consumed alcohol daily (AOR, 1.68; 95% CI, 1.06-2.67). Other independent predictors of HIV were age, number of sex partners, recent migration, and presence of bacterial vaginosis, genital ulcer, active syphilis and herpes simplex virus type 2. CONCLUSION: Development of programs that actively involve men in HIV prevention is important in reducing transmission of HIV in this population. Further, interventions that focus on STI control, the mobile population, sexual risk behavior and responsible alcohol use are required.

Short report: asymptomatic Cryptosporidium hominis infection among human immunodeficiency virus-infected patients in Tanzania.

Few data exist on the relative importance of individual Cryptosporidium species in acquired immunodeficiency syndrome cryptosporidiosis. We characterized 127 inpatients infected with human immunodeficiency virus (HIV) in Tanzania for their CD4 cell count and by stool analysis, including Cryptosporidium immunofluorescence and polymerase chain reaction-restriction fragment length polymorphism. Cryptosporidium was detected in patients both with and without diarrheal symptoms (defined as > or = 3 liquid stools/day, 11 of 61 versus 11 of 66; P = not significant) and was a marker for low CD4 cell count (median = 124/microL versus 212/microL in Cryptosporidium-negative patients; P < 0.04). Cryptosporidium hominis was the predominant species in this region and was associated with a longer duration of symptoms, a higher rate of asymptomatic infection, and a lower CD4 cell count versus C. parvum-infected patients (P < 0.05). This study suggests there may be important differences in the natural history of Cryptosporidium infection in HIV-infected persons depending on parasite species.

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

Chlamydial infection in males and conseqences for their female sexual partners, an example from rural Kilimanjaro, Tanzania.

The aim of this paper is to examine the reproductive health status for the wives of chlamydia-infected, but largely asymptomatic men. In a cross-sectional study in rural Tanzania 447 men and 393 women, aged 15-44 years, were screened for chlamydial infection. The prevalence was 9.6% and 6.9%, respectively. Among 43 chlamydia-positive men, 17 were married. Data from both spouses, independently examined, could be matched for 12 couples. None of the 12 husbands had discharge, one had dysuria and 3 had pyuria. Three wives tested positive for chlamydial infection, two others had pelvic inflammatory disease, four others had pyuria. Men reported more sexual partners than women and were considered being the index case for the chlamydial infection. While three of 11 wives (27%) tested chlamydia-positive from a cervical sample, transmission might have occurred in 5-8 cases (transmission rate (42-67%), indicating that these 12 largely asymptomatic chlamydia-positive men were highly infectious to their sexual partners.

Anaemia among pregnant women in northern Tanzania: prevalence, risk factors and effect on perinatal outcomes.

Anaemia during pregnancy is associated with negative maternal and neonatal outcomes. However, there is limited data regarding prevalence and effects of anaemia during pregnancy in northern Tanzania. The objective of this study was to determine the prevalence and possible risk factors for anaemia and its effect on perinatal outcomes among pregnant women attending antenatal care in Moshi Municipality in northern Tanzania. A cohort of pregnant women aged 14-43 years and in their 3rd trimester, was recruited from two primary health care clinics between June 2002 and March 2004. Interviews, anthropometric measurements and haematological examinations were conducted on 2654 consenting women. Perinatal outcomes were recorded during delivery and at 1 week after delivery. Of the 2654 participants, 47.4% had anaemia (haemoglobin [Hb] <11g/dl), 35.3% had mild anaemia (Hb= 9-10.9g/dl), 9.9% had moderate anaemia (Hb =7- 8.9g/dl), and 2.1% had severe anaemia (Hb < 7 g/dl). Anaemia was significantly more prevalent in HIV-positive (56.4%) than in HIV-negative women (46.7%), (P = 0.01). In logistic regression anaemia was independently associated with maternal HIV (OR= 1.5), malaria (OR= 5.2), clinic of recruitment (OR= 1.5) and low income (OR= 1.9). Pregnant women with anaemia were more likely to have low birth weight (LBW) infants. Compared with non-anaemic women, the risk of LBW was 1.6 times and 4.8 times higher for children born to women with moderate and severe anaemia, respectively. In conclusion, anaemia in pregnancy is a severe public health problem in northern Tanzania. Control of maternal anaemia may be one important strategy to prevent LBW in this setting. Measures to prevent malaria and to control anaemia among all pregnant women irrespective of HIV status, should be strengthened. Outside of the health sector broader approaches for anaemia prevention targeting women of lower income, are required.

Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.

Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.

Patterns of alcohol use, problem drinking, and HIV infection among high-risk African women.

OBJECTIVES: To examine the relationship between patterns of alcohol use and HIV infection and to assess the association between problem drinking and the prevalence of risk factors for HIV among a sample of high-risk African women. METHODS: Baseline data were collected between 2002 and 2003 during enrollment of 1050 women in a prospective cohort study designed to assess risk factors for HIV. Information about demographic and employment characteristics, sexual behaviors, and drinking patterns were obtained by interviews. The CAGE questionnaire was used to assess problem drinking. The association between measures of alcohol use and HIV/STDs and sexual behaviors were summarized using odds ratios, adjusted odds ratios (AOR), and 95% confidence intervals (CI). RESULTS: HIV prevalence was 19.0% (95% CI, 16.6%-21.4%). Overall 73.9% of the women drank alcohol whereas 34.6% were classified as problem drinkers. After adjusting for demographic and employment variables, drinkers were at increased risk to be HIV+ when compared with nondrinkers (AOR, 2.10; 95% CI, 1.29-3.42). Greater involvement with alcohol, as indicated by recency, frequency and quantity consumed, was associated with increased risk. Problem drinkers were at greater risk to be HIV+ than nonproblem drinkers (AOR, 1.79; 95% CI, 1.06-3.04 vs. AOR, 2.43; 95% CI, 1.45-4.06). Problem drinkers were also more likely to have engaged in several types of high-risk sexual behaviors and to have other STD infections including HSV-2. CONCLUSION: Programs aiming at limiting alcohol use or promoting abstinence from alcohol might help to reduce high-risk behaviors and lower the burden of HIV/STDs in this population.

Effect of trimethoprim-sulfamethoxazole prophylaxis on antimicrobial resistance of fecal Escherichia coli in HIV-infected patients in Tanzania.

BACKGROUND: Trimethoprim-sulfamethoxazole (SXT) reduces morbidity and mortality among HIV-infected persons in Africa, but its impact on antimicrobial resistance is of concern. METHODS: HIV-uninfected (group A), HIV-infected but not requiring SXT (group B), and HIV-infected and eligible for SXT (group C) adults were recruited into a prospective observational cohort study in Moshi, Tanzania. Stool was examined for Escherichia coli nonsusceptible to SXT at baseline and at weeks 1, 2, 4, and 24. General estimating equation models were used to assess differences in susceptibility over time and cross-resistance to other antimicrobials. RESULTS: Of 181 subjects, 118 (65.1%) were female and the median (range) age was 36 (20 to 72) years. At baseline, E. coli nonsusceptible to SXT was isolated from 23 (53.5%) of 43 patients in group A, 25 (67.6%) of 37 patients in group B, and 37 (64.9%) of 57 patients in group C. The odds ratios (P value) for SXT nonsusceptibility in group C at weeks 1, 2, 4, and 24 compared with baseline were 3.4 (0.013), 3.0 (0.019), 2.9 (0.030), and 1.5 (0.515), respectively. SXT nonsusceptibility was associated with nonsusceptibility to ampicillin, chloramphenicol, ciprofloxacin, and nalidixic acid (P

Design of a community-based study of sexually transmitted infections/HIV and infertility in an urban area of northern Tanzania.

OBJECTIVE: The objective of this study was to describe the design of a community-based study of sexually transmitted infections (STIs)/HIV and infertility in northern Tanzania. STUDY DESIGN: Households were selected using a 2-stage sampling design. Eligible women and their partners were interviewed before samples were collected for STIs/HIV detection. Posttest counseling and treatment for STIs and infertility were provided. RESULTS: A total of 2019 women and 794 male partners were interviewed. Over 70% of interviewed women and men provided blood and urine samples. Individuals providing blood and urine samples had high-risk profiles for STIs/HIV when compared with others who did not provide these samples. Although the study results may be affected by selection bias, risk factors for STIs/HIV were similar to those in other studies supporting the generalizability of the findings. CONCLUSIONS: It is feasible to conduct a community-based survey, including collection of biomarkers and measurement of infertility, in this urban setting.

The role of herpes simplex virus type 2 and other genital infections in the acquisition of HIV-1 among high-risk women in northern Tanzania.

BACKGROUND: We examined the role of herpes simplex virus type 2 (HSV-2) and other genital infections on human immunodeficiency virus type 1 (HIV-1) incidence in a cohort study conducted between 2002 and 2005 among female bar/hotel workers in Moshi, Tanzania. METHODS: At baseline and every 3 months thereafter, participants were interviewed, and blood and genital samples were collected. Predictors of HIV-1 incidence were evaluated using a Cox proportional hazards regression model. RESULTS: Of 845 women who were HIV-1 seronegative at baseline, 689 (81.5%) were monitored in the study for a total of 698.6 person-years at risk (PYARs). The overall HIV-1 incidence was 4.6/100 PYARs (95% confidence interval [CI], 3.0-6.2/100 PYARs), and condom use was very low. After adjustment for other risk factors, the risk of HIV-1 was increased among women with HSV-2 at baseline (hazard ratio [HR], 4.3 [95% CI, 1.5-12.4]) and in those who acquired HSV-2 during the study period (HR, 5.5 [95% CI, 1.2-25.4]). Other independent predictors of HIV-1 were baseline chlamydial infection (HR, 5.2), bacterial vaginosis (HR, 2.1), and the occurrence of genital ulcers (HR, 2.7). CONCLUSION: HSV-2 and other genital infections were the most important risk factors for HIV-1. Control of these infections could help to reduce HIV-1 incidence in this population.