Leigh Anne Shafer

HIV prevalence and incidence are no longer falling in southwest Uganda: evidence from a rural population cohort 1989-2005.

Background:Throughout the 1990s, HIV-1 prevalence and incidence were falling in Uganda. Recently, some researchers have noticed that HIV-1 prevalence is levelling off. We examine prevalence, incidence, and sexual behaviour trends in a rural population cohort in Uganda over 16 years. Methods:We report prevalence by survey round and incidence by calendar year from a prospective general population cohort study. Using logistic regression Wald tests, we examined casual partners, condom use, and pregnancies. We examined age at sexual debut by means of life tables. Results:HIV-1 prevalence declined from 8.5% in 1990/1991 to 6.2% in 1999/2000, and thereafter rose to 7.7% in 2004/2005. Incidence (per 1000 person-years at risk) fell from 7.5 in 1990 to 4.1 in 1998, and thereafter increased to 5.0 by 2004. The 2005 incidence estimate reached an all-time low of 2.5, but the preliminary 2006 estimate shows a rise again. Incidence trends varied by age and sex. Some sexual behaviour indicators showed more risky behaviour in recent years compared with the 1990s, whereas others indicated that the reduction in risky behaviour that began in the 1990s continues. Conclusion:HIV-1 prevalence is rising in this cohort. Incidence is stabilizing, and shows signs of increasing among some subgroups. The extent to which changing sexual behaviour has played a role in these epidemiological trends is unclear, but it is likely to have contributed. To solidify the success that Uganda had throughout the 1990s in controlling the HIV epidemic, the efforts in HIV prevention need to be re-strengthened, using all strategies known.

Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort.

Objectives:To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort. Methods:HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4+ cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings. Results:Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count >200 cells/μL (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). A V3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006). Conclusions:These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population.

Is sexual risk taking behaviour changing in rural south-west Uganda? Behaviour trends in a rural population cohort 1993–2006

Objective: To describe sexual behaviour trends in a rural Ugandan cohort in the context of an evolving HIV epidemic, 1993–2006. Methods: Sexual behaviour data were collected annually from a population cohort in which HIV serological surveys were also conducted. Behaviour trends were determined using survival analysis and logistic regression. Trends are reported based on the years in which the respective indicators were collected. Results: Between 1993 and 2006, median age at first sex increased from 16.7 years to 18.2 years among 17–20-year-old girls and from 18.5 years to 19.9 years among boys. Both sexes reported a dip in age at sexual debut between 1998 and 2001. One or more casual partners in the past 12 months among men rose from 11.6% in 1997 to 12.7% in 2004 and then declined to 10.2% in 2006. Among women it increased from 1.4% in 1997 to 3.7% in 2004 and then reduced to 1.4% in 2006. The rise in casual partners between 1997 and 2004 was driven mainly by older age groups. Trends in condom use with casual partners varied by age, increasing among those aged 35+ years, declining in the middle age groups and presenting a dip and then a rise in the youngest aged group (13–19 years). Conclusion: Among youth, risky behaviour declined but increased in the late 1990s/early 2000s. Among those aged 35+ years, condom use rose but casual partners also rose. Several indicators portrayed a temporary increase in risk taking behaviour from 1998 to 2002.

Effect of pregnancy on HIV disease progression and survival among women in rural Uganda

Objective  To investigate the effect of pregnancy on HIV disease progression and survival among HIV‐infected women in rural Uganda, prior to the introduction of anti‐retroviral therapy (ART).

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models

Summary Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Funding Canadian Institutes of Health Research.

Anaemia in a rural Ugandan HIV cohort: prevalence at enrolment, incidence, diagnosis and associated factors

Objectives  To determine the prevalence and incidence of anaemia in HIV‐positive and negative individuals; to identify risk factors for anaemia, prior to the introduction of HAART; and to determine the validity of the clinical diagnosis of anaemia.

HIV-1 disease progression and mortality before the introduction of highly active antiretroviral therapy in rural Uganda.

Objective:To provide estimates of survival and progression to different HIV disease endpoints after HIV infection among adults in a rural Ugandan setting. Design:A prospective population-based cohort study. Methods:Eligible individuals at least 15 years of age with documented HIV seroconversion were recruited from a general population cohort in rural Uganda, along with a randomly selected proportion of HIV-prevalent and HIV-negative individuals. All participants were followed up every 3 months, and CD4 cell counts taken every 6 months in HIV-positive participants. Life tables and Kaplan–Meier functions were used to estimate survival patterns for all endpoints [death, time to World Health Organization (WHO) stage 2, 3, AIDS and CD4 cell count < 200 cells/μl]. Analysis of follow-up time was truncated when antiretroviral therapy (ART) became available in the area in January 2004. Results:We recruited 240 HIV incident cases, 108 prevalent cases and 257 HIV-negative controls. Crude mortality rates were 70.0 per 1000 person-years in HIV-positive, and 12.1 per 1000 person-years in HIV-negative individuals. The median time from seroconversion to death was 9.0 years (N = 240) and 6.2 years to a CD4 cell count less than 200 cells/μl or WHO stage 4 (N = 229). The median time from ART eligibility (CD4 cell count < 200 cells/μl, < 350 cells/μl and WHO stage 3, or WHO stage 4) to death was 34.7 months. Older age at seroconversion was a risk factor for faster progression to death and ART eligibility. Conclusion:HIV progression in this African cohort is similar to that reported in industrialized countries before the widespread introduction of ART.

Do behavioural differences help to explain variations in HIV prevalence in adolescents in sub-Saharan Africa?

Objective  To compare adolescent risk factors for HIV infection in two countries with high adolescent HIV prevalence and two lower prevalence countries with the aim of identifying risk factors that may help explain differences in adolescent HIV prevalence.

Using in-depth qualitative data to enhance our understanding of quantitative results regarding the impact of HIV and AIDS on households in rural Uganda

Two significant challenges face researchers tracking HIV-related socio-economic and demographic change over time in large cohort studies. Firstly, data collected in cohort studies established to describe the dynamics of HIV infection may contain no systematic data on household consumption expenditures which is an established measure of current and long-run household welfare. The second challenge is the choice of the unit of analysis in order to recognise and record impact; this is because most cohorts use the household as that unit. This means that the influence of factors outside that unit cannot easily be tracked. In this paper we show how a detailed understanding of the impact of HIV and AIDS on wider families and social networks, obtained through in-depth longitudinal research with a small number of households, can shed light on the findings from quantitative analysis from a larger cohort in the same population in rural Uganda. The findings of large-scale survey data from more than 2000 households over a 12-year period showed a lack of a strong association between poverty, HIV status and/or death of the household head. In-depth ethnographic research with 26 households in 1991/2 and a restudy of the same households in 2006/7 provide insights into the reasons for this finding: the choice of socio-economic indicators and support from other family and community members play a part in affecting survey findings on the impact of HIV at household level. One other factor is important in explaining the findings. HIV-infected family members from outside the household may drain resources from the household, so looking at the impact of HIV and AIDS on peoples wider families provides pointers to why those who have not had an AIDS-related death in their own household may have failed to prosper. Our qualitative findings show that AIDS may well throw households into disarray and poverty, but more often reduces development and hinders families from getting out of poverty. Used strategically, small longitudinal studies can provide important information with which to explain patterns observed in large-scale quantitative datasets.

Changes in PTSD symptomatology and mental health during pregnancy and postpartum.

Changes in mental health symptoms throughout pregnancy and postpartum may impact a woman’s experience and adjustment during an important time. However, few studies have investigated these changes throughout the perinatal period, particularly changes in posttraumatic stress disorder (PTSD) symptoms. The purpose of this study was to examine longitudinal changes in PTSD, depression, and anxiety symptomatology during pregnancy and postpartum. Pregnant women of ethnically diverse backgrounds receiving services for prenatal care at an outpatient obstetric-gynecology clinic or private physicians’ office were assessed by interview on symptoms of PTSD, depression, anxiety, and general stress up to four times, including their first, second, and third trimester, and postpartum visits. Overall, during pregnancy there was a declining trend of PTSD symptoms. For anxiety, there was no overall significant change over time; however, anxiety symptoms were individually variable in the rate of change. For both depression and general stress symptoms, there was a declining trend, which was also variable in the individual rate of change among women during their pregnancy. Visual and post hoc analyses also suggest a possible peak in PTSD symptoms in the weeks prior to delivery. While most mental health symptoms may generally decrease during pregnancy, given the individual variability among women in the rate of change in symptoms, screening and monitoring of symptom fluctuations throughout the course of pregnancy may be needed. Further studies are needed to examine potential spiking of symptoms in the perinatal period.