T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Validation of a modified commercial enzyme-linked immunoassay for detection of human immunodeficiency virus type 1 immunoglobulin G antibodies in saliva.

This study was performed to evaluate the performance of a saliva collection device (OmniSal) and an enzyme-linked immunoassay (EIA) designed for use on serum samples (Detect HIV1/2) to detect human immunodeficiency virus type 1 (HIV-1) antibodies in the saliva of high-risk women in Mombasa, Kenya. The results of the saliva assay were compared to a "gold standard" of a double-EIA testing algorithm performed on serum. Individuals were considered HIV-1 seropositive if their serum tested positive for antibodies to HIV-1 by two different EIAs. The commercial serum-based EIA was modified to test the saliva samples by altering the dilution and lowering the cutoff point of the assay. Using the saliva sample, the EIA correctly identified 102 of the 103 seropositive individuals, yielding a sensitivity of 99% (95% confidence interval [CI], 94 to 100%), and 96 of the 96 seronegative individuals, yielding a specificity of 100% (95% CI, 95 to 100%). In this high-risk population, the positive predictive value of the assay was 100% and the negative predictive value was 99%. We conclude that HIV-1 antibody testing of saliva samples collected with this device and tested by this EIA is of sufficient sensitivity and specificity to make this protocol useful in epidemiological studies.

Effect of circumcision on incidence of human immunodeficiency virus type 1 and other sexually transmitted diseases: a prospective cohort study of trucking company employees in Kenya.

To determine the effect of circumcision status on acquisition of human immunodeficiency virus (HIV) type 1 and other sexually transmitted diseases, a prospective cohort study of 746 HIV-1-seronegative trucking company employees was conducted in Mombasa, Kenya. During the course of follow-up, 43 men acquired HIV-1 antibodies, yielding an annual incidence of 3.0%. The annual incidences of genital ulcers and urethritis were 4.2% and 15.5%, respectively. In multivariate analysis, after controlling for demographic and behavioral variables, uncircumcised status was an independent risk factor for HIV-1 infection (hazard rate ratio [HRR=4.0; 95% confidence interval [CI], 1.9-8.3) and genital ulcer disease (HRR=2.5; 95% CI, 1.1-5.3). Circumcision status had no effect on the acquisition of urethral infections and genital warts. In this prospective cohort of trucking company employees, uncircumcised status was associated with increased risk of HIV-1 infection and genital ulcer disease, and these effects remained after controlling for potential confounders.

Use of nonoxynol-9 and changes in vaginal lactobacilli.

Several in vitro studies have shown nonoxynol-9 (N-9) to be toxic to lactobacilli, especially to strains that produce H2O2. Data from a randomized, double-blind, placebo-controlled crossover trial that investigated the safety and toxicity of 2 weeks of daily vaginal application of an N-9 gel were analyzed, to examine the effect of N-9 use on vaginal lactobacilli and bacterial vaginosis. In vivo, N-9 promoted sustained colonization by H2O2-producing lactobacilli among women already colonized (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-2.7). In addition, use of N-9 for 2 weeks reduced the likelihood of bacterial vaginosis (RR, 0.5; 95% CI, 0.3-1.0). In contrast, N-9 use by women initially colonized only by non-H2O2-producing lactobacilli resulted in loss of vaginal lactobacilli (RR, 2.5; 95% CI, 1.2-5.3). These data suggest that daily use of N-9 does not adversely affect vaginal colonization by H2O2-producing lactobacilli but that such use may promote loss of non-H2O2-producing strains.

Decreased incidence of sexually transmitted diseases among trucking company workers in Kenya: results of a behavioural risk-reduction programme.

OBJECTIVE: To establish a cohort of high-risk individuals suitable for HIV-prevention trials, and to measure changes in sexual behaviour and sexually transmitted disease (STD) incidence after a behavioural intervention. DESIGN: Prospective cohort study in trucking company depots in Mombasa, Kenya. PARTICIPANTS: A total of 556 male HIV-seronegative employees of trucking companies. INTERVENTIONS: HIV serological testing, individual counselling, condom promotion, STD diagnosis and management. MAIN OUTCOME MEASURES: Sexual risk behaviour and symptomatic STD incidence. RESULTS: Using time-trend modelling, significant declines in self-reported high-risk sexual behaviour were demonstrated during a 1-year follow-up. The percentage of men reporting any extramarital sex during the 3-month period prior to a follow-up visit decreased from 49% durig the first quarter of follow-up to 36% during the last quarter (P < 0.001). The decline in reported female sex worker contact was from 12% to 6% (P = 0.001). Approximately 30% of men reported consistent condom use during extramarital sex and this percentage remained unchanged during the study period. The incidence of STD declined from 34 per 100 person years (PY) during the first quarter to 10 per 100 PY during the last quarter (P = 0.001). Significant reductions in gonorrhoea (15 to five cases per 100 PY, P = 0.04), non-gonococcal urethritis (10 to two cases per 100 PY, P = 0.05), and genital ulcer disease (nine to two cases per 100 PY, P = 0.02) were observed. CONCLUSIONS: Among truck company workers who participated in a cohort study in Mombasa, Kenya, there was a significant decrease in sex with high-risk partners, but no change in condom use. The change in heterosexual risk behaviour was accompanied by a significant decrease in incidence of gonorrhoea, non-gonococcal urethritis, and genital ulcer disease.

PIP: 556 male HIV-seronegative male employees of trucking companies in Mombasa, Kenya, were exposed to HIV serological testing, individual counseling, condom promotion, and sexually transmitted disease (STD) diagnosis and management, and returned for at least one follow-up visit in a prospective study to measure changes in sexual behavior and STD incidence after the intervention. There was a significant decrease in sex with high-risk partners over the 1-year period of follow-up, but no change in condom use among study participants; 30% of men reported consistent condom use during extramarital sex throughout the study period. The change in heterosexual risk behavior was accompanied by a significant decrease in the incidence of gonorrhea, nongonococcal urethritis, and genital ulcer disease. The percentage of men reporting extramarital sex decreased from 49% to 36%, while contact with female prostitutes declined from 12% to 6%.