Amato Ojwiya

Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study.

BACKGROUND An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria. METHODS HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements. FINDINGS 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052). INTERPRETATION HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.

Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial

BACKGROUND Treatment of sexually-transmitted infections (STIs) and behavioural interventions are the main methods to prevent HIV in developing countries. We aimed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections. METHODS We randomly allocated all adults living in 18 communities in rural Uganda to receive behavioural interventions alone (group A), behavioural and STI interventions (group B), or routine government health services and community development activities (group C). The primary outcome was HIV-1 incidence. Secondary outcomes were incidence of herpes simplex virus type 2 (HSV2) and active syphilis and prevalence of gonorrhoea, chlamydia, reported genital ulcers, reported genital discharge, and markers of behavioural change. Analysis was per protocol. FINDINGS Compared with group C, the incidence rate ratio of HIV-1 was 0.94 (0.60-1.45, p=0.72) in group A and 1.00 (0.63-1.58, p=0.98) in group B, and the prevalence ratio of use of condoms with last casual partner was 1.12 (95% CI 0.99-1.25) in group A and 1.27 (1.02-1.56) in group B. Incidence of HSV2 was lower in group A than in group C (incidence rate ratio 0.65, 0.53-0.80) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C (active syphilis incidence rate ratio, 0.52, 0.27-0.98; gonorrhoea prevalence ratio, 0.25, 0.10-0.64). INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Uganda, where secular changes are occurring. More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics.

Seven-year trends in HIV-1 infection rates, and changes in sexual behaviour, among adults in rural Uganda

ObjectiveTo assess trends in HIV-1 infection rates and changes in sexual behaviour over 7 years in rural Uganda. MethodsAn adult cohort followed through eight medical–serological annual surveys since 1989–1990. All consenting participants gave a blood sample and were interviewed on sexual behaviour. ResultsOn average, 65% of residents gave a blood sample at each round. Overall HIV-1 prevalence declined from 8.2% at round 1 to 6.9% at round 8 (P = 0.008). Decline was most evident among men aged 20–24 years (11.7 to 3.6%;P < 0.001) and women aged 13–19 (4.4% to 1.4%;P = 0.003) and 20–24 (20.9% to 13.8%;P = 0.003). However, prevalence increased significantly among women aged 25–34 (13.1% to 16.6%;P = 0.04). Although overall incidence declined from 7.7/1000 person-years (PY) in 1990 to 4.6/1000 PY in 1996, neither this nor the age-sex specific rates changed significantly (P > 0.2). Age-standardized death rates for HIV-negative individuals were 6.5/1000 PY in 1990 and 8.2/1000 PY in 1996; corresponding rates for HIV-positive individuals were 129.7 and 102.7/1000 PY, respectively. There were no significant trends in age-adjusted death rates during follow-up for either group. There was evidence of behaviour change towards increase in condom use in males and females, marriage at later age for girls, later sexual debut for boys and a fall in fertility especially among unmarried teenagers. ConclusionsThis is the first general population cohort study showing overall long-term significant reduction in HIV prevalence and parallel evidence of sexual behaviour change. There are however no significant reductions in either HIV incidence or mortality.

Declining HIV-1 incidence and associated prevalence over 10 years in a rural population in south-west Uganda: a cohort study

BACKGROUND In Uganda, there have been encouraging reports of reductions in HIV-1 prevalence but not in incidence, which is the most reliable measure of epidemic trends. We describe HIV-1 incidence and prevalence trends in a rural population-based cohort between 1989 and 1999. METHODS We surveyed the adult population of 15 neighbouring villages for HIV-1 infection using annual censuses, questionnaires, and serological surveys. We report crude annual incidence rates by calendar year and prevalence by survey round. FINDINGS 6566 HIV-1 seronegative adults were bled two or more times between January, 1990, and December, 1999, contributing 31984 person years at risk (PYAR) and 190 seroconversions. HIV-1 incidence fell from 8.0 to 5.2 per 1000 PYAR between 1990 and 1999 (p=0.002, chi(2) for trend). Significant sex-specific and age-group-specific reductions in incidence were evident. Incidence was 37% lower for 1995-99 than for 1990-94 (p=0.002, t-test). On average, 4642 adult residents had a definite HIV-1 serostatus at each yearly survey round. HIV-1 prevalence fell significantly between the first and tenth annual survey rounds (p=0.03, chi(2) for trend), especially among men aged 20-24 years (6.5% to 2.2%) and 25-29 years (15.2% to 10.9%) and women aged 13-19 years (2.8% to 0.9%) and 20-24 years (19.3% to 10.1%) (all p<0.001, chi(2) for trend). INTERPRETATION Our findings of a significant drop in adult HIV-1 incidence in rural Ugandans give hope to AIDS control programmes elsewhere in sub-Saharan Africa where rates of HIV-1 infection remain high.

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.

Comparison of STD prevalences in the Mwanza, Rakai, and Masaka trial populations: the role of selection bias and diagnostic errors

Objectives: To assess bias in estimates of STD prevalence in population based surveys resulting from diagnostic error and selection bias. To evaluate the effects of such biases on STD prevalence estimates from three community randomised trials of STD treatment for HIV prevention in Masaka and Rakai, Uganda and Mwanza, Tanzania. Methods: Age and sex stratified prevalences of gonorrhoea, chlamydia, syphilis, HSV-2 infection, and trichomoniasis observed at baseline in the three trials were adjusted for sensitivity and specificity of diagnostic tests and for sample selection criteria. Results: STD prevalences were underestimated in all three populations because of diagnostic errors and selection bias. After adjustment, gonorrhoea prevalence was higher in men and women in Mwanza (2.8% and 2.3%) compared to Rakai (1.1% and 1.9%) and Masaka (0.9% and 1.8%). Chlamydia prevalence was higher in women in Mwanza (13.0%) compared to Rakai (3.2%) and Masaka (1.6%) but similar in men (2.3% in Mwanza, 2.7% in Rakai, and 2.2% in Masaka). Prevalence of trichomoniasis was higher in women in Mwanza compared to women in Rakai (41.9% versus 30.8%). Herpes simplex virus type 2 (HSV-2) seroprevalence and prevalence of serological syphilis (TPHA+/RPR+) were similar in the three populations but the prevalence of high titre syphilis (TPHA+/RPR ≥1:8) in men and women was higher in Mwanza (5.6% and 6.3%) than in Rakai (2.3% and 1.4%) and Masaka (1.2% and 0.7%). Conclusions: Limited sensitivity of diagnostic and screening tests led to underestimation of STD prevalence in all three trials but especially in Mwanza. Adjusted prevalences of curable STD were higher in Mwanza than in Rakai and Masaka.

Sexual networks in Uganda: mixing patterns between a trading town, its rural hinterland and a nearby fishing village.

The study was based in south-west Uganda where significant differences in HIV prevalence have been found between urban and rural areas. Longitudinal data collected in a diary format was used to determine the extent to which high-risk men and women living in a truck stop/trading town had sexual contact with people from surrounding rural areas and a nearby fishing village. Study participants were 143 men, 75 of whom were resident in the town, 40 in a fishing village and 28 in rural areas, and 81 women, of whom 47 were resident in the town, 25 in the fishing village and 9 in a rural area. During 1687 man weeks the 143 men made 3149 trips and had 5189 sexual contacts. Ninety-two per cent of these sexual contacts occurred in the mans current place of residence and 21% were with a new partner. The 81 women participated for 1280 women weeks during which they recorded 6378 sexual contacts. Women who lived in the fishing village and the rural area had around 90% of their contacts with local men while those who lived in the town fell into 3 categories: women who charged a relatively high price for commercial sex had only 11% of contacts with men living in the town, while those who charged a tenth of the price had 71% of contacts with town men. The small number of women who fell into an intermediate category, in terms of price, had sexual contact with a wide variety of men. These findings show that there is little scope for HIV infection to spread between different residential or occupational groups. This may help to explain how large differences in HIV seropositivity between neighbouring localities can be maintained for long periods, despite considerable social and economic mixing between groups and high levels of sexual partner change within groups.

HIV-1 epidemic trends in rural south-west Uganda over a 10-year period

The objective of this study was to examine the epidemic trends of HIV‐1 infection in a rural population cohort in Uganda followed for 10 years. The methods used were to assess incidence and prevalence trends in adults in this longitudinal cohort study. The results showed that incidence of infection has fallen significantly in all adults, and separately in males, females, young adults and older adults over the course of the study period. There was also a reduction in prevalence, especially in young men and women. There was some evidence of a cohort effect in women. The conclusions are that this study provides the first evidence of a falling incidence in a rural general population in Africa. This was an observational cohort exposed to national health education messages, giving hope that similar campaigns elsewhere in Africa could be used effectively in efforts to control the HIV epidemic.

The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults

Objectives  To investigate the effects of malaria parasitaemia and clinical malaria on mortality in HIV seropositive and seronegative adults.