Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study.

BACKGROUND: Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants' consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2-6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3-1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9-4.6] log10 copies/mL versus 3.7 [3.2-4.3], p = 0.017. CONCLUSIONS/SIGNIFICANCE: We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.

Health & Demographic Surveillance System Profile: The Magu Health and Demographic Surveillance System (Magu HDSS).

The Magu Health and Demographic Surveillance System (Magu HDSS) is part of Kisesa OpenCohort HIV Study located in a rural area of North-Western Tanzania. Since its establishment in 1994, information on pregnancies, births, marriages, migrations and deaths have been monitored and updated between one and three times a year by trained fieldworkers. Other research activities implemented in the cohort include: sero surveys which have been conducted every 2-3 years to collect socioeconomic data, HIV sero status and health knowledge attitude and behaviour in adults aged 15 years or more living in the area; verbal autopsy (VA) interviews conducted to establish cause of death in all deaths encountered in the area; Llnking data collected at health facilities to community-based data; monitoring voluntary counselling and testing (VCT); and assessing uptake of antiretroviral treatment (ART). In addition, within the community, qualitative studies have been conducted to address issues linked to HIV stigma, the perception of ART access and adherence.In 2014, the population was over 35 000 individuals. Magu HDSS has contributed to Tanzanian estimates of fertility and mortality, and is a member of the INDEPTH network. Demographic data for Magu HDSS are available via the INDEPTH Network's Sharing and Accessing Repository (iSHARE) and applications to access HDSS data for collaborative analysis are encouraged.

Correlation of serum and dried blood spot results for quantitation of Schistosoma circulating anodic antigen: a proof of principle.

Circulating anodic antigen (CAA) testing is a powerful, increasingly-used tool for diagnosis of active schistosome infection. We sought to determine the feasibility and reliability of measuring CAA in blood spots collected on Whatman 903 protein saver cards, which are the predominant filter papers used worldwide for dried blood spot (DBS) research and clinical care. CAA was eluted from blood spots collected from 19 individuals onto Whatman 903 cards in Mwanza, Tanzania, and the assay was optimized to achieve CAA ratios comparable to those obtained from the spots' corresponding serum samples. The optimized assay was then used to determine the correlation of serum samples (n=16) with DBS from cards that had been stored for 8 years at ambient temperature. Using a DBS volume equivalent to approximately four times the quantity of serum, CAA testing in DBS had a sensitivity of 76% and a specificity of 79% compared to CAA testing in serum. CAA testing was reliable in samples eluted from Whatman 903 cards that had been stored for 8 years at ambient temperature. The overall kappa coefficient was 0.53 (standard error 0.17, p<0.001). We conclude that CAA can be reliably and accurately measured in DBS collected onto the filter paper that is most commonly used for clinical care and research, and that can be stored from prolonged periods of time. This finding opens new avenues for future work among more than 700million individuals living in areas worldwide in which schistosomes are endemic.

Using HIV-attributable mortality to assess the impact of antiretroviral therapy on adult mortality in rural Tanzania.

BACKGROUND: The Tanzanian national HIV care and treatment programme has provided free antiretroviral therapy (ART) to HIV-positive persons since 2004. ART has been available to participants of the Kisesa open cohort study since 2005, but data to 2007 showed a slow uptake of ART and a modest impact on mortality. Additional data from the 2010 HIV serological survey provide an opportunity to update the estimated impact of ART in this setting. METHODS: The Kisesa Health and Demographic Surveillance Site (HDSS) has collected HIV serological data and demographic data, including verbal autopsy (VA) interviews since 1994. Serological data to the end of 2010 were used to make two estimates of HIV-attributable mortality, the first among HIV positives using the difference in mortality between HIV positives and HIV negatives, and the second in the population using the difference between the observed mortality rate in the whole population and the mortality rate among the HIV negatives. Four time periods (1994-1999, 2000-2004, 2005-2007, and 2008-2010) were used and HIV-attributable mortality estimates were analysed in detail for trends over time. A computer algorithm, InterVA-4, was applied to VA data to estimate the HIV-attributable mortality for the population, and this was compared to the estimates from the serological survey data. RESULTS: Among HIV-positive adults aged 45-59 years, high mortality rates were observed across all time periods in both males and females. In HIV-positive men, the HIV-attributable mortality was 91.6% (95% confidence interval (CI): 84.6%-95.3%) in 2000-2004 and 86.3% (95% CI: 71.1%-93.3%) in 2008-2010, while among women, the HIV-attributable mortality was 87.8% (95% CI: 71.1%-94.3%) in 2000-2004 and 85.8% (95% CI: 59.6%-94.4%) in 2008-2010. In the whole population, using the serological data, the HIV-attributable mortality among men aged 30-44 years decreased from 57.2% (95% CI: 46.9%-65.3%) in 2000-2004 to 36.5% (95% CI: 18.8%-50.1%) in 2008-2010, while among women the corresponding decrease was from 57.3% (95% CI: 49.7%-63.6%) to 38.7% (95% CI: 27.4%-48.2%). The HIV-attributable mortality in the population using estimates from the InterVA model was lower than that from HIV sero-status data in the period prior to ART, but slightly higher once ART became available. DISCUSSION: In the Kisesa HDSS, ART availability corresponds with a decline in adult overall mortality, although not as large as expected. Using InterVA to estimate HIV-attributable mortality showed smaller changes in HIV-related mortality following ART availability than the serological results.

Adjusting the HIV prevalence for non-respondents using mortality rates in an open cohort in northwest Tanzania.

OBJECTIVE: To estimate HIV prevalence in adults who have not tested for HIV using age-specific mortality rates and to adjust the overall population HIV prevalence to include both tested and untested adults. METHODS: An open cohort study was established since 1994 with demographic surveillance system (DSS) and five serological surveys conducted. Deaths from Kisesa DSS were used to estimate mortality rates and 95% confidence intervals by HIV status for 3- 5-year periods (1995-1999, 2000-2004, and 2005-2009). Assuming that mortality rates in individuals who did not test for HIV are similar to those in tested individuals, and dependent on age, sex and HIV status and HIV, prevalence was estimated. RESULTS: In 1995-1999, mortality rates (per 1000 person years) were 43.7 (95% CI 35.7-53.4) for HIV positive, 2.6 (95% CI 2.1-3.2) in HIV negative and 16.4 (95% CI 14.4-18.7) in untested. In 2000-2004, mortality rates were 43.3 (95% CI 36.2-51.9) in HIV positive, 3.3 (95% CI 2.8-4.0) in HIV negative and 11.9 (95% CI 10.5-13.6) in untested. In 2005-2009, mortality rates were 30.7 (95% CI 24.8-38.0) in HIV positive, 4.1 (95% CI 3.5-4.9) in HIV negative and 5.7 (95% CI 5.0-6.6) in untested residents. In the three survey periods (1995-1999, 2000-2004, 2005-2009), the adjusted period prevalences of HIV, including the untested, were 13.5%, 11.6% and 7.1%, compared with the observed prevalence in the tested of 6.0%, 6.8 and 8.0%. The estimated prevalence in the untested was 33.4%, 21.6% and 6.1% in the three survey periods. CONCLUSION: The simple model was able to estimate HIV prevalence where a DSS provided mortality data for untested residents.

Does the Spectrum model accurately predict trends in adult mortality? Evaluation of model estimates using empirical data from a rural HIV community cohort study in North-Western Tanzania.

INTRODUCTION: Spectrum epidemiological models are used by UNAIDS to provide global, regional and national HIV estimates and projections, which are then used for evidence-based health planning for HIV services. However, there are no validations of the Spectrum model against empirical serological and mortality data from populations in sub-Saharan Africa. METHODS: Serologic, demographic and verbal autopsy data have been regularly collected among over 30,000 residents in north-western Tanzania since 1994. Five-year age-specific mortality rates (ASMRs) per 1,000 person years and the probability of dying between 15 and 60 years of age (45Q15,) were calculated and compared with the Spectrum model outputs. Mortality trends by HIV status are shown for periods before the introduction of antiretroviral therapy (1994-1999, 2000-2005) and the first 5 years afterwards (2005-2009). RESULTS: Among 30-34 year olds of both sexes, observed ASMRs per 1,000 person years were 13.33 (95% CI: 10.75-16.52) in the period 1994-1999, 11.03 (95% CI: 8.84-13.77) in 2000-2004, and 6.22 (95% CI; 4.75-8.15) in 2005-2009. Among the same age group, the ASMRs estimated by the Spectrum model were 10.55, 11.13 and 8.15 for the periods 1994-1999, 2000-2004 and 2005-2009, respectively. The cohort data, for both sexes combined, showed that the 45Q15 declined from 39% (95% CI: 27-55%) in 1994 to 22% (95% CI: 17-29%) in 2009, whereas the Spectrum model predicted a decline from 43% in 1994 to 37% in 2009. CONCLUSION: From 1994 to 2009, the observed decrease in ASMRs was steeper in younger age groups than that predicted by the Spectrum model, perhaps because the Spectrum model under-estimated the ASMRs in 30-34 year olds in 1994-99. However, the Spectrum model predicted greater 45Q15 mortality than observed in the cohort,although the reasons for this over-estimate are unclear [corrected].

Do accurate HIV and antiretroviral therapy knowledge, and previous testing experiences increase the uptake of HIV voluntary counselling and testing? Results from a cohort study in rural Tanzania.

BACKGROUND: Despite the introduction of free antiretroviral therapy (ART), the use of voluntary counselling and testing (VCT) services remains persistently low in many African countries. This study investigates how prior experience of HIV and VCT, and knowledge about HIV and ART influence VCT use in rural Tanzania. METHODS: In 2006-7, VCT was offered to study participants during the fifth survey round of an HIV community cohort study that includes HIV testing for research purposes without results disclosure, and a questionnaire covering knowledge, attitudes and practices around HIV infection and HIV services. Categorical variables were created for HIV knowledge and ART knowledge, with "good" HIV and ART knowledge defined as correctly answering at least 4/6 and 5/7 questions about HIV and ART respectively. Experience of HIV was defined as knowing people living with HIV, or having died from AIDS. Logistic regression methods were used to assess how HIV and ART knowledge, and prior experiences of HIV and VCT were associated with VCT uptake, with adjustment for HIV status and socio-demographic confounders. RESULTS: 2,695/3,886 (69%) men and 2,708/5,575 women (49%) had "good" HIV knowledge, while 613/3,886 (16%) men and 585/5575 (10%) women had "good" ART knowledge. Misconceptions about HIV transmission were common, including through kissing (55% of women, 43% of men), or mosquito bites (42% of women, 34% of men).19% of men and 16% of women used VCT during the survey. After controlling for HIV status and socio-demographic factors, the odds of VCT use were lower among those with poor HIV knowledge (aOR = 0.5; p = 0.01 for men and aOR = 0.6; p < 0.01 for women) and poor ART knowledge (aOR = 0.8; p = 0.06 for men, aOR = 0.8; p < 0.01 for women), and higher among those with HIV experience (aOR = 1.3 for men and aOR = 1.6 for women, p < 0.01) and positive prior VCT experience (aOR = 2.0 for all men and aOR = 2.0 for HIV-negative women only, p < 0.001). CONCLUSIONS: Two years after the introduction of free ART in this setting, misconceptions regarding HIV transmission remain rife and knowledge regarding treatment is worryingly poor, especially among women and HIV-positive people. Further HIV-related information, education and communication activities are urgently needed to improve VCT uptake in rural Tanzania.

Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: secondary analyses of pooled community-based data from the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA).

BACKGROUND: Model-based estimates of the global proportions of maternal deaths that are in HIV-infected women range from 7% to 21%, and the effects of HIV on the risk of maternal death is highly uncertain. We used longitudinal data from the Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA) network to estimate the excess mortality associated with HIV during pregnancy and the post-partum period in sub-Saharan Africa. METHODS: The ALPHA network pooled data gathered between June, 1989 and April, 2012 in six community-based studies in eastern and southern Africa with HIV serological surveillance and verbal-autopsy reporting. Deaths occurring during pregnancy and up to 42 days post partum were defined as pregnancy related. Pregnant or post-partum person-years were calculated for HIV-infected and HIV-uninfected women, and HIV-infected to HIV-uninfected mortality rate ratios and HIV-attributable rates were compared between pregnant or post-partum women and women who were not pregnant or post partum. FINDINGS: 138,074 women aged 15-49 years contributed 636,213 person-years of observation. 49,568 women had 86,963 pregnancies. 6760 of these women died, 235 of them during pregnancy or the post-partum period. Mean prevalence of HIV infection across all person-years in the pooled data was 17.2% (95% CI 17.0-17.3), but 60 of 118 (50.8%) of the women of known HIV status who died during pregnancy or post partum were HIV infected. The mortality rate ratio of HIV-infected to HIV-uninfected women was 20.5 (18.9-22.4) in women who were not pregnant or post partum and 8.2 (5.7-11.8) in pregnant or post-partum women. Excess mortality attributable to HIV was 51.8 (47.8-53.8) per 1000 person-years in women who were not pregnant or post partum and 11.8 (8.4-15.3) per 1000 person-years in pregnant or post-partum women. INTERPRETATION: HIV-infected pregnant or post-partum women had around eight times higher mortality than did their HIV-uninfected counterparts. On the basis of this estimate, we predict that roughly 24% of deaths in pregnant or post-partum women are attributable to HIV in sub-Saharan Africa, suggesting that safe motherhood programmes should pay special attention to the needs of HIV-infected pregnant or post-partum women. FUNDING: Wellcome Trust, Health Metrics Network (WHO).

Low rates of repeat HIV testing despite increased availability of antiretroviral therapy in rural Tanzania: findings from 2003-2010.

BACKGROUND: HIV counselling and testing (HCT) services can play an important role in HIV prevention by encouraging safe sexual behaviours and linking HIV-infected clients to antiretroviral therapy (ART). However, regular repeat testing by high-risk HIV-negative individuals is important for timely initiation of ART as part of the 'treatment as prevention' approach. AIM: To investigate HCT use during a round of HIV serological surveillance in northwest Tanzania in 2010, and to explore rates of repeat testing between 2003 and 2010. METHODS: HCT services were provided during the fourth, fifth and sixth rounds of serological surveillance in 2003-2004 (Sero-4), 2006-2007 (Sero-5) and 2010 (Sero-6). HCT services have also been available at a government-run health centre and at other clinics in the study area since 2005. Questionnaires administered during sero-surveys collected information on socio-demographic characteristics, sexual behaviour and reported previous use of HCT services. RESULTS: The proportion of participants using HCT increased from 9.4% at Sero-4 to 16.6% at Sero-5 and 25.5% at Sero-6. Among participants attending all three sero-survey rounds (n = 2,010), the proportions using HCT twice or more were low, with 11.1% using the HCT service offered at sero-surveys twice or more, and 25.3% having tested twice or more if reported use of HCT outside of sero-surveys was taken into account. In multivariable analyses, individuals testing HIV-positive were less likely to repeat test than individuals testing HIV-negative (aOR 0.17, 95% CI 0.006-0.52). DISCUSSION/CONCLUSIONS: Although HCT service use increased over time, it was disappointing that the proportions ever testing and ever repeat-testing were not even larger, considering the increasing availability of HCT and ART in the study area. There was some evidence that HIV-negative people with higher risk sexual behaviours were most likely to repeat test, which was encouraging in terms of the potential to pick-up those at greatest risk of HIV-infection.

Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network.

BACKGROUND: Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population. METHODS: Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin's rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person's knowledge of their own HIV status which would become more widespread in the latter time period. RESULTS: Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89) than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03). DISCUSSION: Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner.

Trends in the uptake of voluntary counselling and testing for HIV in rural Tanzania in the context of the scale up of antiretroviral therapy.

OBJECTIVES: To describe trends in voluntary counselling and testing (VCT) use and to assess whether high-risk and infected individuals are receiving counselling and learning their HIV status in rural Tanzania. METHODS: During two rounds of linked serological surveys (2003-2004 and 2006-2007) with anonymous HIV testing among adults, VCT was offered to all participants. The crude and adjusted odds ratios for completing VCT in each survey were calculated to compare uptake by demographic, behavioural and clinical characteristics, stratified by sex. Repeat testing patterns were also investigated. RESULTS: The proportion of participants completing VCT increased from 10% in 2003-2004 to 17% in 2006-2007, and among HIV-infected persons from 14% to 25%. A higher proportion of men than women completed VCT in both rounds, but the difference declined over time. Socio-demographic and behavioural factors associated with VCT completion were similar across rounds, including higher adjusted odds of VCT with increasing numbers of sexual partners in the past 12 months. The proportion having ever-completed VCT reached 26% among 2006-2007 attendees, with repeat testing rates highest among those aged 35-44 years. Among 3923 participants attending both rounds, VCT completion in 2006-2007 was 17% among 3702 who were HIV negative in both rounds, 19% among 124 who were HIV infected in both rounds and 22% among 96 who seroconverted between rounds. CONCLUSION: VCT services are attracting HIV-infected and high-risk individuals. However, 2 years after the introduction of antiretroviral therapy, the overall uptake remains low. Intensive mobilisation efforts are needed to achieve regular and universal VCT use.

Using age-specific mortality of HIV infected persons to predict anti-retroviral treatment need: a comparative analysis of data from five African population-based cohort studies.

OBJECTIVES: To present a simple method for estimating population-level anti-retroviral therapy (ART) need that does not rely on knowledge of past HIV incidence. METHODS: A new approach to estimating ART need is developed based on calculating age-specific proportions of HIV-infected adults expected to die within a fixed number of years in the absence of treatment. Mortality data for HIV-infected adults in the pre-treatment era from five African HIV cohort studies were combined to construct a life table, starting at age 15, smoothed with a Weibull model. Assuming that ART should be made available to anyone expected to die within 3 years, conditional 3-year survival probabilities were computed to represent proportions needing ART. The build-up of ART need in a successful programme continuously recruiting infected adults into treatment as they age to within 3 years of expected death was represented by annually extending the conditional survival range. RESULTS: The Weibull model: survival probability in the infected state from age 15 = exp(-0.0073 × (age - 15)(1.69)) fitted the pooled age-specific mortality data very closely. Initial treatment need for infected persons increased rapidly with age, from 15% at age 20-24 to 32% at age 40-44 and 42% at age 60-64. Overall need in the treatment of naïve population was 24%, doubling within 5 years in a programme continually recruiting patients entering the high-risk period for dying. CONCLUSION: A reasonable projection of treatment need in an ART naive population can be made based on the age and gender profile of HIV-infected people.

The impact of antiretroviral therapy on adult mortality in rural Tanzania.

OBJECTIVE: To describe the impact of antiretroviral therapy (ART) on mortality rates among adults participating in an HIV community cohort study in north-west Tanzania. METHODS: Serological and demographic surveillance rounds have been undertaken in a population of approximately 30,000 people since 1994. Free HIV care including ART has been available since 2005. Event history analysis was used to compare mortality rates among HIV-negative and HIV-positive adults in the 5-year period before and after the introduction of ART. Crude and adjusted hazard ratios were calculated using exponential regression models. Interaction between time period and HIV status was assessed to investigate whether there was a non-linear relationship between these two variables. RESULTS: Male and female mortality patterns varied over the pre- and post-ART period. In women, the crude death rate fell for both HIV negatives and HIV positives hazard rate ratio (HRR = 0.71; 95%CI 0.51-0.99 and HRR = 0.68; 95%CI: 0.46-0.99, respectively). For men, the mortality among the HIV negatives increased (HRR = 1.47; 95%CI: 1.06-2.03) while the decline in mortality among the HIV positives (HRR = 0.77; 95%CI 0.52-1.13) was not statistically significant. The largest decrease in HIV-positive mortality over the two periods was among the 30- to 44-year-old age group for women and among the 45- to 59-year-old age group for men. CONCLUSION: There has been a modest effect on mortality in the study population following the introduction of free ART 5 years ago. Improving access to treatment and placing greater focus on retaining individuals on treatment are essential if the full potential of treatment for reducing HIV-related mortality is to be realised.

Trends in HIV & syphilis prevalence and correlates of HIV infection: results from cross-sectional surveys among women attending ante-natal clinics in Northern Tanzania.

BACKGROUND: Sentinel surveillance for HIV in ante-natal clinics (ANC) remains the primary method for collecting timely trend data on HIV prevalence in most of sub-Saharan Africa. We describe prevalence of HIV and syphilis infection and trends over time in HIV prevalence among women attending ante-natal clinics (ANC) in Magu district and Mwanza city, part of Mwanza region in Northern Tanzania. HIV prevalence from ANC surveys in 2000 and 2002 was 10.5% and 10.8% respectively. In previous rounds urban residence, residential mobility, the length of time sexually active before marriage, time since marriage and age of the partner were associated with HIV infection. METHODS: A third round of HIV sentinel surveillance was conducted at ante-natal clinics in Mwanza region, Tanzania during 2006. We interviewed women attending 27 ante-natal clinics. In 15 clinics we also anonymously tested women for syphilis and HIV infection and linked these results to the questionnaire data. RESULTS: HIV prevalence was 7.6% overall in 2006 and 7.4% at the 11 clinics used in previous rounds. Geographical variations in HIV prevalence, apparent in previous rounds, have largely disappeared but syphilis prevalence is still higher in rural clinics. HIV prevalence has declined in urban clinics and is stable in rural clinics. The correlates of HIV infection have changed over time. In this round older age, lower gravidity, remarriage, duration of marriage, sexual activity before marriage, long interval between last birth and pregnancy and child death were all associated with infection. CONCLUSIONS: HIV prevalence trends concur with results from a community-based cohort in the region. Correlates of HIV infection have also changed and more proximate, individual level factors are now more important, in line with the changing epidemiology of infection in this population.

Separation of spouses due to travel and living apart raises HIV risk in Tanzanian couples.

BACKGROUND: Persons with absent partners may be more vulnerable to risky sexual behavior and therefore HIV. Partner absence can be due to traveling (e.g., family visits or funerals) or to living apart (e.g., work-related or in polygamous marriages). We investigated to what extent partner absence leads to more risky sexual behavior in Tanzanian couples. METHODS: We compared 95 men and 85 women living apart with 283 men and 331 women living together. Only persons who were still married were included, either living apart or cohabiting at the time of the interview. Subjects were classified into 4 groups: coresidents being either nonmobile or mobile, and people living apart either frequently or infrequently seeing each other. RESULTS: Most people living apart were polygamously married. Men living apart did not report more extramarital sex than coresident men. However, among coresident men, extramarital sex was reported by 35% of those being mobile compared with 15% of those nonmobile. Among women, those living apart reported extramarital sex more often than coresidents (14% vs. 7%), and this was mainly due to women living apart who infrequently saw their husbands. CONCLUSIONS: Risky sexual behavior occurs more often in mobile coresident men, and in women living apart infrequently seeing their spouses. These groups are relatively easy to identify and need extra attention in HIV prevention campaigns.

Uptake of HIV voluntary counselling and testing services in rural Tanzania: implications for effective HIV prevention and equitable access to treatment.

OBJECTIVE: To describe the associations between socio-demographic, behavioural and clinical characteristics and the use of HIV voluntary counselling and testing (VCT) services among residents in a rural ward in Tanzania. METHODS: Eight thousand nine hundred and seventy participants from a community-based cohort were interviewed, provided blood for research HIV testing, and were offered VCT. Univariate and multivariate logistic regression was used to identify socio-demographic, clinical and behavioural factors associated with VCT use. RESULTS: Although 31% (1246/3980) of men and 24% (1195/4990) of women expressed an interest in the service, only 12% of men and 7% of women subsequently completed VCT. Socio-demographic factors, such as marital status, area of residence, religion and ethnicity influenced VCT completion among males and females in different ways, while self-perceived risk of HIV, prior knowledge of VCT, and sex with a high-risk partner emerged as important predictors of VCT completion among both sexes. Among males only, those infected with HIV for 5 years or less tended to self-select for VCT compared to HIV-negatives (adjusted odds ratio = 1.43; 95% CI: 0.99-2.14). This contributed to a higher proportion of HIV-positive males knowing their status compared to HIV-positive females. CONCLUSIONS: In this setting, a disproportionate number of HIV-positive women are failing to learn their status, which has implications for equitable access to onward referral for care and treatment services. Evidence that some high-risk behaviours may prompt VCT use is encouraging, although further interventions are required to improve knowledge about HIV risk and the benefits of VCT. Targeted interventions are also needed to promote VCT uptake among married women and rural residents.

Survival after HIV infection in the pre-antiretroviral therapy era in a rural Tanzanian cohort.

BACKGROUND: Survival patterns after HIV infection in African populations in the era before antiretroviral therapy (ART) form an important baseline for measuring future successes of treatment programmes. Few studies have followed seroconverters for 10 or more years to describe such patterns. METHODS: The Kisesa open cohort study conducted four rounds of village-based HIV testing and 20 rounds of household-based demographic surveillance between 1994 and 2006. Approximate infection dates were established for individual seroconverters by allocating a date between the last negative and first positive test. Person-years lived post-infection were computed, allowing for left truncation and right censoring, and Kaplan-Meier survival functions were constructed, truncating the analysis at the start of 2005 when ART first became available in the community. Weibull models were fitted to estimate median survival time, and parametric regression methods were used to investigate the influence of sex and age at infection. RESULTS: A total of 369 seroconverters were identified, providing 890 person-years of follow-up during which 44 deaths were observed. The Kaplan-Meier function showed 67% surviving 9 years post-infection, and the overall predicted median survival was 11.5 years. Survival was strongly related to age at infection (hazard ratio 1.06 for each additional year of age, and weakly to sex. A strong effect of age was evident even after allowing for mortality from non-HIV-related causes using cause deletion methods to estimate net mortality. CONCLUSION: The survival of HIV-infected individuals was comparable to that reported in developed country studies before the introduction of HAART. Survival patterns in Kisesa are marginally more favourable than those reported in cohort studies in Uganda.

HIV prevalence and incidence in rural Tanzania: results from 10 years of follow-up in an open-cohort study.

BACKGROUND: Tanzanian antenatal clinic surveillance data suggest stabilizing HIV levels. Data from an open cohort in northern Tanzania provide robust estimates of prevalence and incidence. METHODS: Between 1994 and 2004, 19 rounds of household-based demographic surveillance and 4 rounds of individually linked HIV serologic surveys were conducted. Longitudinal knowledge of individuals' testing histories is used to allow for effects of selective participation on prevalence estimates; multiple imputation procedures allow for interval censoring effects on incidence. RESULTS: A total of 16,820 adults donated blood for HIV testing in at least 1 of 4 serologic surveys. HIV prevalence increased steadily from 6.0% in 1994/1995 to 8.3% in 2000/2001, leveling out thereafter. HIV incidence increased sharply from 0.8% in 1994 to 1997 to 1.2% per thousand in 1997 to 2000, remaining high (1.1%) in 2000 to 2003. In roadside areas, incidence fell in the last interval, especially among women, but in remote rural areas, incidence rose slightly. CONCLUSIONS: HIV spread is continuing in rural areas, suggesting a need for more intensive HIV prevention efforts and antiretroviral interventions. The leveling off in prevalence is attributable to a combination of high mortality among HIV-infected persons and a slight decrease in incidence in roadside villages.

The effects of high HIV prevalence on orphanhood and living arrangements of children in Malawi, Tanzania, and South Africa.

Using longitudinal data from three demographic surveillance systems (DSS) and a retrospective cohort study, we estimate levels and trends in the prevalence and incidence of orphanhood in South Africa, Tanzania, and Malawi in the period 1988-2004. The prevalence of maternal, paternal, and double orphans rose in all three populations. In South Africa - where the HIV epidemic started later, has been very severe, and has not yet stabilized - the incidence of orphanhood among children is double that of the other populations. The living arrangements of children vary considerably between the populations, particularly in relation to fathers. Patterns of marriage, migration, and adult mortality influence the living and care arrangements of orphans and non-orphans. DSS data provide new insights into the impact of adult mortality on children, challenging several widely held assumptions. For example, we find no evidence that the prevalence of child-headed households is significant or has increased in the three study areas.

Age-specific mortality patterns in HIV-infected individuals: a comparative analysis of African community study data.

OBJECTIVES: Describe age-specific mortality patterns of HIV-infected adults in African communities before introduction of HAART. METHODS: Mortality data (deaths and person-years observed) for HIV-positive subjects aged 15-65 from six African community studies in five different countries were pooled, combining information from 1793 seroconverters and 8534 HIV positive when first tested. Age-specific mortality hazards were modelled using parametric regression based on the Weibull distribution, to investigate effects of sex, and site-specific measures of mean age at incidence, crude mortality rate of uninfected, and measures of epidemic maturity. RESULTS: The combined studies yielded a total of 31 777 person-years of observation for HIV-positive subjects, during which time 2602 deaths were recorded. Mortality rates rose almost linearly with age, from below 50/1000 at ages < 20 years, up to 150/1000 at 50 years +. There was no significant difference between men and women in level or age pattern of mortality. Weibull regression analysis suggested that intersite variation could be explained by HIV prevalence trend, and by the ratio of HIV proportional mortality to current HIV prevalence. A model representation was constructed with a common age pattern of mortality, but allowing the level to be adjusted by specifying HIV prevalence indicators. CONCLUSION: The linear age trend of mortality in HIV-infected populations was satisfactorily represented by a Weibull function providing a parametric model adaptable for representing different levels of HIV-related mortality. This model might be simpler to use in demographic projections of HIV-affected populations than models based on survival post-infection.