George W. Rutherford

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda

Background:The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. Objective:To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. Design and methods:A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants’ HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. Results:Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2–0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. Conclusions:Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

Using respondent-driven sampling methodology for HIV biological and behavioral surveillance in international settings: a systematic review.

To determine operational and analytical characteristics of respondent-driven sampling (RDS) in international settings and to explore factors that may affect recruitment of most-at-risk populations using RDS, we reviewed HIV biological and behavioral surveillance studies that used this method outside of the United States. We identified 123 eligible studies, 59 from Europe, 40 from Asia and the Pacific, 14 from Latin America, seven from Africa and three from Oceania. Studies collectively recruited 32,298 participants between 2003 and 2007; 53% of studies were conducted among injecting drug users, which generally had faster recruitment compared with studies among sex workers. All but 13 studies reached ≥90% of their intended sample size, and six studies failed to reach equilibrium for key variables. This review has shown that RDS is an effective technique, when designed and implemented appropriately, to sample most-at-risk populations for HIV biological and behavioral surveys.

DURATION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION BEFORE DETECTION OF ANTIBODY

To estimate the duration and frequency of the period of HIV infection without detectable antibody, modelling techniques were applied to results of detection of HIV DNA by means of the polymerase chain reaction (PCR) and to data from cases in published reports. PCR was carried out with gag and env region primers on samples from 27 homosexual and 12 haemophilic men for whom stored samples were available from before and after seroconversion; serum was also tested for p24 antigen by antigen-capture enzyme immunoassay. HIV DNA was detectable before seroconversion in 4 men; in all 4 PCR was positive only in the seronegative sample taken closest to the time of seroconversion. In 3 men antigen was detected before seroconversion; in each case HIV DNA was also detected. By a Markov model, the time from infection with HIV (as assessed by detection of HIV DNA) to first detection of HIV antibody was estimated to be 2.4 (SE 2.1) months for the median individual. Modelling of cases of HIV infection with known exposure in published reports gave a median estimate of 2.1 (0.1) months from exposure to antibody detection, and 95% of cases would be expected to seroconvert within 5.8 (0.6) months. HIV infection for longer than 6 months without detectable antibody seems uncommon.

A Meta-analysis of the Effect of High Weight on Asthma

Background: Prevalence rates for both overweight and asthma have been increasing among children in developed countries over the past two decades. Some recent studies have postulated a causal relation between these but have lacked power to form a definitive conclusion. Aim: To estimate the effect of high body weight in childhood on the future risk of asthma. Methods: Medline search (1966 to October 2004), supplemented by manual search of reference lists and grey literature. Cohort studies that examined high body weight at birth or during childhood and future outcome of asthma were included. Data from each study were extracted on exposure status, clinical outcome, and study characteristics. Results: A total of 402 studies were initially identified, of which 12 met the inclusion criteria. The combined results from four studies that examined the effect of high body weight during middle childhood on the outcome of subsequent asthma showed a 50% increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from nine studies that examined the effect of high birth weight on subsequent asthma had a pooled RR of 1.2 (95% CI 1.1 to 1.3). There was consistency among the results in sensitivity analyses examining studies containing only estimates of odds ratios, studies containing only the outcome of physician diagnosis of asthma, and studies including all definitions of high body weight. Conclusions: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. Potential biological mechanisms include diet, gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal influences. Further research might elucidate the causal pathway, which could improve our understanding of the pathophysiology of asthma and perhaps lead to knowledge of potential preventive interventions.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men : three San Francisco epidemiological cohorts

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposis sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CD 17.5–23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% Cl 4.1–7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposis sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P < 0.05). The prevalence of erythematous candidiasis and Kaposis sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Course of HIV-I infection in a cohort of homosexual and bisexual men: An 11 year follow up study

OBJECTIVE--To characterise the natural history of sexually transmitted HIV-I infection in homosexual and bisexual men. DESIGN--Cohort study. SETTING--San Francisco municipal sexually transmitted disease clinic. PATIENTS--Cohort included 6705 homosexual and bisexual men originally recruited from 1978 to 1980 for studies of sexually transmitted hepatitis B. This analysis is of 489 cohort members who were either HIV-I seropositive on entry into the cohort (n = 312) or seroconverted during the study period and had less than or equal to 24 months between the dates of their last seronegative and first seropositive specimens (n = 177). A subset of 442 of these men was examined in 1988 or 1989 or had been reported to have developed AIDS. MAIN OUTCOME MEASURES--Development of clinical signs and symptoms of HIV-I infection, including AIDS, AIDS related complex, asymptomatic generalised lymphadenopathy, and no signs or symptoms of infection. MEASUREMENTS AND MAIN RESULTS--Of the 422 men examined in 1988 or 1989 or reported as having AIDS, 341 had been infected from 1977 to 1980; 49% (167) of these men had died of AIDS, 10% (34) were alive with AIDS, 19% (65) had AIDS related complex, 3% (10) had asymptomatic generalised lymphadenopathy, and 19% (34) had no clinical signs or symptoms of HIV-I infection. Cumulative risk of AIDS by duration of HIV-I infection was analysed for all 489 men by the Kaplan-Meier method. Of these 489 men, 226 (46%) had been diagnosed as having AIDS. We estimated that 13% of cohort members will have developed AIDS within five years of seroconversion, 51% within 10 years, and 54% within 11.1 years. CONCLUSION--Our analysis confirming the importance of duration of infection to clinical state and the high risk of AIDS after infection underscores the importance of continuing efforts both to prevent transmission of HIV-I and to develop further treatments to slow or stall the progression of HIV-I infection to AIDS.

Implementation Challenges to Using Respondent-Driven Sampling Methodology for HIV Biological and Behavioral Surveillance: Field Experiences in International Settings

Using respondent-driven sampling (RDS), we gathered data from 128 HIV surveillance studies conducted outside the United States through October 1, 2007. We examined predictors of poor study outcomes, reviewed operational, design and analytical challenges associated with conducting RDS in international settings and offer recommendations to improve HIV surveillance. We explored factors for poor study outcomes using differences in mean sample size ratios (recruited/calculated sample size) as the outcome variable. Ninety-two percent of studies reported both calculated and recruited sample sizes. Studies of injecting drug users had a higher sample size ratio compared with other risk groups. Study challenges included appropriately defining eligibility criteria, structuring social network size questions, selecting design effects and conducting statistical analysis. As RDS is increasingly used for HIV surveillance, it is important to learn from past practical, theoretical and analytical challenges to maximize the utility of this method.

The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease

Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.

Prevalence incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda.

Background: Tuberculosis (TB) is the leading cause of death among people with HIV in sub-Saharan Africa. Expanding access to antiretroviral therapy (ART) may reduce the burden of TB, but to what extent is unknown. Methods: In a study of 1044 adults who initiated home-based ART in Tororo, Uganda between 1 May 2003 and 30 June 2005, participants were screened for active TB at baseline and then monitored at weekly home visits. Participants with TB at baseline or follow-up were compared with those without TB to determine factors associated with mortality in those with TB. Results: At baseline, 75 (7.2%) subjects had TB and a total of 53 (5.5%) were diagnosed with TB over a median of 1.4 years of follow-up (3.90 cases/100 person years). Cumulative mortality was 17.9/100 person-years for those with TB and 3.8/100 person-years for those without TB (P < 0.001). Mortality was associated with low baseline CD4 cell counts [relative hazard (RH), 0.99 per 1 cell/μl increase; P = 0.03] and marginally associated with a body mass index ≤ 18 (RH, 2.04; P = 0.10) and increasing age (RH, 1.04 per year; P = 0.11). TB incidence and TB-associated mortality were highest within the first 6 months of ART and declined to 52% and 61% of expected values, respectively, from months 7 to 18 after ART initiation. Conclusion: TB remains an important cause of illness and death in patients receiving ART in Uganda. However, both appear to decline markedly, after 6 months of ART.

Risk Factors for Injuries from in-Line Skating and the Effectiveness of Safety Gear

BACKGROUND Of the estimated 22.5 million people participating in in-line skating in the United States in 1995, about 100,000 were sufficiently injured so as to require emergency department care. We investigated the effectiveness of wrist guards, elbow pads, knee pads, and helmets in preventing skating injuries. METHODS We used data from the 91 hospital emergency departments participating in the National Electronic Injury Surveillance System, a national probability sample of randomly selected hospitals with 24-hour emergency departments. Injured in-line skaters who sought medical attention between December 1992 and July 1993 were interviewed by telephone. We conducted a case-control study of skaters who injured their wrists, elbows, knees, or heads as compared with skaters with injuries to other parts of their bodies. RESULTS Of 206 eligible injured subjects, 161 (78 percent) were interviewed. Wrist injuries were the most common (32 percent); 25 percent of all injuries were wrist fractures. Seven percent of injured skaters wore all the types of safety gear; 46 percent wore none. Forty-five percent wore knee pads, 33 percent wrist guards, 28 percent elbow pads, and 20 percent helmets. The odds ratio for wrist injury, adjusted for age and sex, for those who did not wear wrist guards, as compared with those who did, was 10.4 (95 percent confidence interval, 2.9 to 36.9). The odds ratio for elbow injury, adjusted for the number of lessons skaters had had and whether or not they performed trick skating, was 9.5 (95 percent confidence interval, 2.6 to 34.4) for those who did not wear elbow pads. Non-use of knee pads was associated with a nonsignificant increase in the risk of knee injury (crude odds ratio, 2.2; 95 percent confidence interval, 0.7 to 7.2). The effectiveness of helmets could not be assessed. CONCLUSIONS Wrist guards and elbow pads are effective in protecting in-line skaters against injuries.