A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.

BACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. METHODS: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). RESULTS: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). CONCLUSIONS: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania.

BACKGROUND: few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. METHODS: we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4(+) T lymphocyte count (CD4 cell count). RESULTS: of 403 patients enrolled, the median age was 38 years (range, 14-96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/µL (range, 1-1,105 cells/ µL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). CONCLUSIONS: while Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania.

OBJECTIVE: To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. METHODS: During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined. RESULTS: A total of 467 patients were enrolled whose median age was 2 years (range 2 months-13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. CONCLUSION: Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.

Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection.

BACKGROUND: An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. METHODS: Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. RESULTS: The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-gamma response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-gamma production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. CONCLUSIONS: The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.

Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey.

BACKGROUND: Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria. METHODS: Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures. RESULTS: The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI). Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144%) in uninfected donors. All donors showed a response towards IL-1beta production, drawing special attention for its possible protective role in early innate immune responses to malaria. CONCLUSIONS: In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries.

Total lymphocyte count and World Health Organization pediatric clinical stage as markers to assess need to initiate antiretroviral therapy among human immunodeficiency virus-infected children in Moshi, Northern Tanzania.

BACKGROUND: The World Health Organization (WHO) has recommended the use of clinical staging alone and with total lymphocyte count to identify HIV infected children in need of antiretroviral therapy (ART) in resource-limited settings, when CD4 cell count is not available. METHODS: We prospectively enrolled children obtaining care for HIV infection at the Kilimanjaro Christian Medical Centre Pediatric Infectious Diseases Clinic in Moshi, Tanzania between March 2004 and May 2006 for this cohort study. RESULTS: One hundred ninety two (89.7%) of 214 children met WHO ART initiation criteria based on clinical staging or CD4 cell count. Several low-cost measures identified individuals who met WHO ART initiation criteria to the following degree: WHO stages 3 or 4 had 87.5% (95% CI, 82.8-92.1) sensitivity and, by definition, 100% (CI, 100-100) specificity; WHO recommended advance disease TLC cutoffs: sensitivity = 23.9% (95% CI, 17.3-30.5) specificity = 78.2% (95% CI, 67.3-89.1). Low TLC was a common finding, (50 of 214; 23%); however, it did not improve the sensitivity or specificity of clinical staging in identifying the severely immunosuppressed stage 2 children. Growth failure or use of total lymphocyte counts in isolation were not reliable indicators of severe immunosuppression or need to initiate ART. CONCLUSION: The use of total lymphocyte count does not improve the ability to identify children in need of ART compared with clinical staging alone. Low absolute lymphocyte count did not correlate with severe immunosuppression based on CD4 cell count in this cohort.

Validation, performance under field conditions, and cost-effectiveness of Capillus HIV-1/HIV-2 and determine HIV-1/2 rapid human immunodeficiency virus antibody assays using sequential and parallel testing algorithms in Tanzania.

Rapid human immunodeficiency virus (HIV) antibody tests support the effort to expand access to HIV testing and counseling services in remote, rural, and poor parts of the world. We validated the Capillus HIV-1/HIV-2 (Trinity Biotech PLC, Bray, County Wicklow, Ireland) and Determine HIV-1/2 (Abbott Laboratories, Abbott Park, IL) rapid tests in a reference laboratory using patient samples from Tanzania and evaluated the performance of the tests under field conditions in northern Tanzania. We used the resulting data to study sequential and parallel testing algorithms. In the validation study, sensitivity, specificity, the predictive value of a positive test (PV(+)), and the predictive value of a negative test (PV(-)) were all 100% for Capillus and Determine. In the field evaluation among 12,737 clients, sensitivity, specificity, PV(+), and PV(-) were 99.7%, 99.8%, 98.7%, and 99.9%, respectively, for Capillus and 99.6%, 99.9%, 99.5%, and 99.9%, respectively, for Determine. A sequential testing algorithm that did not confirm a negative initial Capillus result with a Determine result cost $7.77 per HIV diagnosis but missed 0.3% of HIV infections. A sequential testing algorithm that did not confirm a negative initial Determine result with a Capillus result cost $7.64 per HIV diagnosis but missed 0.4% of HIV infections. A parallel testing algorithm cost $13.46 per HIV diagnosis but detected more HIV-infected clients.

Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania.

BACKGROUND: Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence, virologic failure, and antiviral drug resistance is essential to achieving long-term success. METHODS: A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment, and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level >400 copies/mL; for patients with an HIV RNA level >1000 copies/mL, genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. RESULTS: A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR], 19.8; P<.01) and the proportion of months receiving self-funded treatment (AOR, 23.5; P=.04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR, 3.6; P=.03) and the proportion of months receiving self-funded antiretroviral therapy (AOR, 13.0; P=.02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR, 0.10; P=.04). CONCLUSIONS: Self-funded treatment was associated with incomplete adherence and virologic failure, and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure.

Mass treatment with single-dose azithromycin for trachoma.

BACKGROUND: Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness. Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model. METHODS: We collected conjunctival swabs for quantitative polymerase-chain-reaction assay of C. trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic. For ethical reasons, at 6, 12, and 18 months, we gave tetracycline eye ointment to residents who had clinically active trachoma. RESULTS: At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment. The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at 2 months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pretreatment level at 2 months and 0.8 percent at 24 months. At each time point after baseline, over 90 percent of the total community burden of C. trachomatis infection was found among subjects who had been positive the previous time they were tested. CONCLUSIONS: The prevalence and intensity of infection fell dramatically and remained low for two years after treatment. One round of very-high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C. trachomatis infection.

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.

Antiretroviral treatment literacy among HIV voluntary counseling and testing clients in Moshi, Tanzania, 2003 to 2005.

Antiretroviral treatment literacy leads to greater HIV testing and treatment and antiretroviral treatment adherence. Among northern Tanzanian subjects, antiretroviral treatment awareness was only 17%. Factors associated with low antiretroviral treatment literacy included having exchanged money or gifts for sex, living in rural areas, having more than 2 children, and having a primary education only. Previous HIV testing was protective against low antiretroviral treatment literacy. These results support refocusing HIV education efforts and increasing synergy between HIV prevention and treatment programs.

Capacity of health-care facilities to deliver HIV treatment and care services, Northern Tanzania, 2004.

Few data exist on the current capacity of Tanzanian health-care facilities to deliver antiretroviral therapy (ART). We evaluated this capacity among Northern Zone facilities in 2004 using a questionnaire that addressed human resources, clinical facilities and services, and laboratory capacity. Of 19 facilities surveyed, nine (47%) had staff trained to manage ART and three (16%) prescribed ART. Two (11%) offered CD4 counts, five (26%) offered liver function tests, 16 (84%) offered chest radiography, and 18 (95%) offered acid-fast sputum staining. Of 12 (67%) facilities offering outpatient HIV/AIDS services, 12 (100%) provided co-trimoxazole to outpatients and six (50%) provided isoniazid (INH). All 19 (100%) facilities offered rapid HIV tests and full blood pictures. Overall in 2004, facilities needed strengthening to increase staff training in ART management and to implement INH for treatment of latent tuberculosis. Laboratory facilities for ART monitoring were inadequate, and outpatient ART was limited.

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.

Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries.

As a result of the scale-up of antiretroviral treatment (ART) programmes and substantial financial support worldwide, an increasing number of HIV-infected individuals in low-income and middle-income countries (LIMCs) now have access to ART. Despite this progress, important questions remain on the best use of ART and how patients should be maintained on a successful regimen. This Review addresses some of the issues faced by those managing the epidemic in LMICs, including when to start treatment, choice of first-line ART, and when to switch regimens. Although the first priority must be continued expansion of access to ART, there should be a move towards starting ART earlier to treat individuals before they reach advanced stages of disease, to reduce early mortality, and to build support for improved monitoring of treatment failure. There is also a need for more randomised controlled studies to identify the long-term outcomes, cost-effectiveness of ART, and use of virological monitoring in LMICs.

Evaluation of the Abbott m2000rt RealTime HIV-1 assay with manual sample preparation compared with the ROCHE COBAS AmpliPrep/AMPLICOR HIV-1 MONITOR v1.5 using specimens from East Africa.

The performance of the Abbott m2000rt RealTime HIV-1 assay (RealTime HIV-1) with manual sample preparation was compared against the ROCHE COBAS AmpliPrep/AMPLICOR HIV-1 MONITOR Test v1.5 (CAP/CA HIV-1) using samples collected from 100 donors infected with HIV and 20 donors not infected with HIV in northern Tanzania where HIV-1 subtypes A, C, D, and their recombinant forms predominate. The RealTime HIV-1 appeared to have more within-run variability at high HIV-1 RNA concentrations, but total assay variability over the dynamic range tested was within the manufacturer's claim of <0.3 SD copies/mL. Accuracy studies showed 100% concordance for positive and negative values. When continuous values were examined, CAP/CA HIV-1 yielded higher values than the RealTime HIV-1 at higher nominal HIV-1 RNA concentrations. The RealTime HIV-1 assay showed excellent linearity between 2.5 and 7.0 log copies/mL. Of negative samples, 100% showed negative results, and >95% of samples with nominal concentrations of 40 copies/mL were detected at > or = 40 copies/mL by RealTime HIV-1. Manual sample preparation may contribute to higher total assay variability. This study suggests that the Abbott m2000rt RealTime HIV-1 assay with manual sample preparation is an acceptable and feasible alternative to the conventional ROCHE COBAS AmpliPrep/AMLICOR HIV-1 Monitor v1.5 assay and that the RealTime HIV-1 assay performs well on samples from East Africa.

Characteristics of HIV voluntary counseling and testing clients before and during care and treatment scale-up in Moshi, Tanzania.

OBJECTIVES: We evaluated changes in characteristics of clients presenting for voluntary counseling and testing (VCT) before and during care and treatment center (CTC) scale-up activities in Moshi, Tanzania, between November 2003 and December 2007. METHODS: Consecutive clients were surveyed after pretest counseling, and rapid HIV antibody testing was performed. Trend tests were used to assess changes in seroprevalence and client characteristics over time. Multivariable logistic regression models were used to estimate the contribution of changes in sociodemographic and behavioral risk characteristics, and symptoms, to changes in seroprevalence before and during CTC scale-up. RESULTS: Data from 4391 first-time VCT clients were analyzed. HIV seroprevalence decreased from 26.2% to 18.9% after the availability of free antiretroviral therapy and expansion of CTCs beyond regional and referral hospitals. Seroprevalence decreased by 27 % for females (P = 0.0002) and 34% for males (P = 0.0125). Declines in seropositivity coincided with decreases in symptoms among males and females (P < 0.0001) and a more favorable distribution of sociodemographic risks among females (P = 0.002). No changes in behavioral risk characteristics were observed. CONCLUSIONS: Concurrent with the scale-up of CTCs, HIV seroprevalence and rates of symptoms declined sharply at an established freestanding VCT site in Moshi, Tanzania. If more HIV-infected persons access VCT at sites where antiretrovirals are offered, freestanding VCT sites may become a less cost-effective means for HIV case finding.

Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

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

Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania.

BACKGROUND: Monogamy, together with abstinence, partner reduction, and condom use, is widely advocated as a key behavioral strategy to prevent HIV infection in sub-Saharan Africa. We examined the association between the number of sexual partners and the risk of HIV seropositivity among men and women presenting for HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/ PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS service organization in Moshi, Tanzania were surveyed between November 2003 and December 2007. Data on sociodemographic characteristics, reasons for testing, sexual behaviors, and symptoms were collected. Men and women were categorized by number of lifetime sexual partners, and rates of seropositivity were reported by category. Factors associated with HIV seropositivity among monogamous males and females were identified by a multivariate logistic regression model. Of 6,549 clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40). 939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among 1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV infection was 19% and 4%, respectively (p<0.0001). The risk increased monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for women and men, respectively with 5 or more partners. In multivariate analysis, HIV seropositivity among monogamous women was most strongly associated with age (p<0.0001), lower education (p<0.004), and reporting a partner with other partners (p = 0.015). Only age was a significant risk factor for monogamous men (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of partners is strongly associated with rates of seropositivity; however, even women reporting lifetime monogamy have a high risk for HIV infection. Partner reduction should be coupled with efforts to place tools in the hands of sexually active women to reduce their risk of contracting HIV.