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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.

Assessments of the importance of different routes of HIV-1 (HIV) transmission are vital for prioritization of control efforts. Lack of consistent direct data and large uncertainty in the risk of HIV transmission from HIV-contaminated injections has made quantifying the proportion of transmission caused by contaminated injections in sub-Saharan Africa difficult and unavoidably subjective. Depending on the risk assumed, estimates have ranged from 2.5% to 30% or more. We present a method based on an age-structured transmission model that allows the relative contribution of HIV-contaminated injections, and other routes of HIV transmission, to be robustly estimated, both fully quantifying and substantially reducing the associated uncertainty. To do this, we adopt a Bayesian perspective, and show how prior beliefs regarding the safety of injections and the proportion of HIV incidence due to contaminated injections should, in many cases, be substantially modified in light of age-stratified incidence and injection data, resulting in improved (posterior) estimates. Applying the method to data from rural southwest Uganda, we show that the highest estimates of the proportion of incidence due to injections are reduced from 15.5% (95% credible interval) (0.7%, 44.9%) to 5.2% (0.5%, 17.0%) if random mixing is assumed, and from 14.6% (0.7%, 42.5%) to 11.8% (1.2%, 32.5%) under assortative mixing. Lower, and more widely accepted, estimates remain largely unchanged, between 1% and 3% (0.1-6.3%). Although important uncertainty remains, our analysis shows that in rural Uganda, contaminated injections are unlikely to account for a large proportion of HIV incidence. This result is likely to be generalizable to many other populations in sub-Saharan Africa.

Background: Previous studies have found that in Africa, a greater risk of HIV infection is often found in groups with higher educational attainment. However, some serial cross-sectional studies have found greater reductions in HIV prevalence among more educated groups, especially in cohorts of young adults. More recent studies have found some instances where higher schooling levels are associated with lower HIV prevalence., Methods: We describe changes in the association between schooling levels, HIV prevalence and condom use in a rural population-based cohort between 1989/1990 and 1999/2000, in Masaka District, Uganda., Results: In 1989-1990, higher educational attainment was associated with higher risk of HIV-1 infection, especially among males, but once odds ratios are adjusted for age, no significant relation between schooling and HIV infection remains. In 1999-2000, there is, for females aged 18-29 years, a significant relationship between higher educational attainment and lower HIV prevalence, even after adjustment for age, gender, marital status and wealth (P for trend 0.01). Tests for interaction, significant for males and both genders combined, show that more schooling has been shifting towards an association with less HIV infection between 1989-1990 and 1999-2000, especially for young individuals. Condom use increased during the study period and this increase has been concentrated among more educated individuals., Conclusions: These findings suggest that over a decade more educated young adults, especially females, have become more likely to respond to HIV/AIDS information and prevention campaigns by effectively reducing their sexual risk behaviour.

About 30 million people in Africa are estimated to be living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), yet data about the natural history of infection on the continent are sparse. We reviewed the literature on the natural history of HIV-1 and HIV-2 infections among African adults. Only one study, conducted in rural Uganda, has reported on survival from the time of HIV-1 seroconversion: the median was 9.8 years, which is similar to that reported in developed countries in the early stages of the epidemic and consistent with the findings from the follow-up of individuals identified by serological testing during community-based prevalence studies from Africa. Progression to symptomatic disease was faster in Uganda than in developed countries, due largely to the high background level of morbidity. Various studies suggest that people infected with HIV-2 survive longer and the course of the disease is possibly more variable than in people infected with HIV-1. However no studies have investigated survival from time of seroconversion among people infected with HIV-2. The majority of patients in hospital in Africa with either HIV-1 or HIV-2 have the clinical features of AIDS just before they die, and many are severely immunosuppressed. This is similar to the situation in developed countries before the introduction of highly active antiretroviral therapy (HAART). Potentially preventable infections are the leading causes of death among individuals infected with HIV-1. Prophylactic regimens and better treatments could have some effect on survival, but major improvements in life expectancy will require HAART.

It is unclear how human immunodeficiency virus (HIV) type 1-specific immune responses in exposed seronegative (ESN) individuals differ from those in HIV-1-infected subjects. By use of overlapping peptides spanning Gag, Tat, Nef, Vif, Vpr, and Vpu, peripheral blood mononuclear cells from ESN individuals, their seropositive (SP) partners, and unexposed seronegative control subjects were screened for interferon- gamma production. Responses were more frequent (95.7% vs. 20%), of a higher magnitude (9-fold), and of wider breadth (median number of peptides recognized, 18 vs. 2.5) in SP than in ESN individuals. Peptides recognized by ESN individuals were less frequently recognized by their SP partners. SP subjects infrequently recognized peptides from Vif, and such responses were subdominant; among ESN individuals, this HIV-1 protein was most frequently recognized. Immunodominant peptides recognized by SP subjects tended to be from relatively conserved regions, whereas peptides recognized by ESN individuals were associated with slow disease progression.

The CD45 (leucocyte common) antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor signalling in lymphocytes, and expression of different CD45 isoforms is associated with distinct functions. Here we describe a novel polymorphism in exon 4 (A54G) of the gene encoding CD45 (PTPRC) that results in an amino acid substitution of Thr-19 to Ala in exon 4. The 54G allele was identified in African Ugandan populations and was found with a suggestive but not statistically significant increase in frequency amongst HIV-seropositive Ugandans. This suggests that the 54G variant and CD45 splicing abnormalities might be associated with HIV infection.

Objectives: To estimate the association between HIV disease progression and the incidence of recognized pregnancy; to estimate the risk of subsequent fetal loss., Methods: A total of 191 women (92 HIV seropositive and 99 HIV seronegative at enrolment) aged 15-49 years in an HIV clinical cohort were invited to attend routine clinic visits every 3 months. Information on HIV progression collected at the visit was related to whether there was a pregnancy beginning in the following 3 months. Visits were excluded where the woman was already pregnant, lactating, using modern contraceptives or if there was inadequate follow-up., Results: There were 2524 eligible visits and 216 recognized pregnancies. The reported frequency of sexual intercourse diminished with advancing HIV disease. The adjusted odds ratio (OR) for pregnancy when the woman was in WHO stage 1 compared with HIV seronegatives was 0.58 [95% confidence interval (CI), 0.36-0.93]; stage 2, 0.47 (95% CI, 0.25-0.91); stage 3, 0.43 (95% CI, 0.25-0.74); and stage 4, (AIDS) 0.14 (95% CI, 0.02-1.09). The findings were similar for CD4 cell count, time from seroconversion and time before AIDS. There was an increase in fetal loss from the early stages of HIV infection (adjusted OR for stage 1, 5.38; 95% CI, 1.57-18.44), there were very few recognized pregnancies in the advanced stages., Conclusions: Fertility is reduced from the earliest asymptomatic stage of HIV infection resulting from both a reduced incidence of recognized pregnancy and increased fetal loss. The greatest reduction in fertility was observed following progression to AIDS when there was a very low incidence of recognized pregnancies.

CD4(+) T cell help is important for the functionality of CD8(+) cytotoxic T-lymphocytes (CTLs) in limiting viral replication and may contribute to mediation of apparent resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Using five HIV-1 antigens in an intracellular cytokine assay, the presence of specific antigen-responsive interferon- gamma-positive (IFN-gamma(+)) CD69(+) CD4(+) T-lymphocytes was evaluated in ESNs, their seropositive partners, and unexposed seronegative controls. Ten ESNs (five females, five uncircumcised males) were identified from 10 HIV-1 serodiscordant couples with a history of frequent unprotected sexual intercourse. All ESNs and controls were negative on two EIAs and for HIV-1 proviral DNA. The frequency of ESNs with antigen-responsive IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes ranged from three to five of eight for the different HIV-1 antigens. Six of eight ESNs tested had a positive response to at least one of the five antigens. Responses were on average 3.5 times higher among seropositives compared to ESNs and absent in the five unexposed controls. A negative correlation was noted between responses in ESNs and the plasma viral load of their seropositive spouse. Clade-specific and cross-clade reactivity were noted in both ESNs and seropositive partners tested. The findings confirm that ESNs are in a state of HIV-1-specific immune activation and suggest that HIV-1-specific IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes in addition to HIV-1-specific CD8(+) CTLs already described by others are potential immunological correlates of protection from persistent HIV-1 infection.

The effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression was investigated in 1045 adults in Uganda. At enrollment and every 6 months, a clinical history, examination, and laboratory investigations that included CD4 cell counts were done. HIV-1 envelope subtype was assessed mainly by peptide serology supplemented by heteroduplex mobility assay and DNA sequencing. A multivariate analysis of survival was performed to assess the prognostic value of HIV-1 subtype on death. A marginal general linear model also determined the effect of subtype on CD4 cell count during follow-up. Subtype D was associated with faster progression to death (relative risk, 1.29; 95% confidence interval, 1.07-1.56; P=.009) and with a lower CD4 cell count during follow-up (P=.001), compared with subtype A, after adjusting for CD4 cell count at enrollment. In Africa, envelope subtype D is associated with faster disease progression, compared with subtype A.

We compared HIV-1 RNA levels using the nucleic acid sequenced based amplification (NASBA) test kit in 2 samples taken one year apart from participants infected with env subtype A or D in a population-based cohort in Uganda. Fifty participants were infected with subtype A and 70 with subtype D. HIV-1 RNA levels were significantly higher in subtype D unadjusted (P=0.001), and after adjusting for age, gender, and CD4 count (P<0.001). Eighty-six participants had HIV-1 RNA measurements in both years and 67 (78%) were within one log10 of their result a year before. There was no relationship between the difference in log viral load and proportion of CD4 change. Individuals infected with subtype D had a higher average increase in viral load and this was statistically significant if adjusted for baseline levels and CD4 count (P=0.015). [ABSTRACT FROM AUTHOR]