Amplified HIV transmission during early-stage infection.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
Richard J Hayes
Publications and source records attributed to Richard J Hayes.
Association of genital shedding of herpes simplex virus type 2 and HIV-1 among sex workers in rural Zimbabwe.
INTRODUCTION: Herpes simplex virus type 2 (HSV-2) facilitates sexual acquisition of HIV-1 but data on transmission are less clear. In this study the interaction between genital shedding of HIV-1 and HSV-2 was explored among Zimbabwean sex workers. METHODS: Women (n = 214) were interviewed about genital symptoms. Blood samples were analysed for HIV-1 and HSV-2 antibodies, HIV-1 plasma viral load (PVL) and CD4 lymphocyte count and genital swabs for detection of HIV-1 and HSV-2 genital shedding, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, and a cervico-vaginal lavage (CVL) for quantitative measurement of HIV-1 shedding. Shedding analyses were undertaken on women co-infected with HSV-2 and HIV-1. RESULTS: A total of 124 women were co-infected with HIV-1 and HSV-2; 58 were infected with HSV-2 alone. Most HIV-1-infected women were co-infected with HSV-2 (95.4%). Genital HIV-1 shedding was detected in 84.3% of co-infected women and was associated with low CD4 cell count and high PVL but not with reported symptoms of genital herpes or genital shedding of HSV-2. There was no difference in HIV-1 shedding among women shedding HSV-2 (79.3%) and women not shedding HSV-2 (83.2%) (P = 0.64). The adjusted odds ratio for HIV-1 shedding between HSV-2 shedders and non-shedders was 0.8 [95% confidence interval (CI), 0.2-3.3]. HIV-1 PVL(log10) and CVL viral load(log10) were correlated (r = 0.38; 95%CI, 0.2-0.5). After adjusting for PVL, genital symptoms and age, HSV-2 shedding had no effect on CVL viral load (P = 0.13). CONCLUSION: Rate and quantity of HIV-1 genital shedding do not appear to be altered by presence of HSV-2 genital shedding.
Adolescent↗
Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.
OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.
Female↗
'The man who believed he had AIDS was cured': AIDS and sexually-transmitted infection treatment-seeking behaviour in rural Mwanza, Tanzania.
Most people living with AIDS in sub-Saharan Africa have had neither a biomedical diagnosis nor antiretroviral medication, leading to the question of how individuals understand and treat AIDS. This study examined general illness, sexually-transmitted infection (STI) and AIDS treatment-seeking behaviour in rural Mwanza, Tanzania. From 1999-2002, participant observation was carried out in nine villages for a total of 158 person-weeks. Treatments were pluralistic and opportunistic, usually beginning with home remedies (western or traditional), followed by visits to traditional healers (THs) and/or health facilities (HFs). THs were sometimes preferred over HFs because of familiarity, trust, accessibility, expense, payment plans, and the perceived cause, nature and severity of the illness, e.g. only THs were believed to successfully treat bewitchment. Some people, particularly young girls, delayed or avoided seeking treatment for STIs for fear of stigma. Most STIs were attributed to natural causes, but AIDS was sometimes attributed to witchcraft. Locally available biomedical care of people with AIDS-like symptoms consisted of basic treatment of opportunistic infections. Most such individuals repeatedly visited THs and HFs, but many stopped attending HFs because they came to believe they could not be cured there. Some THs claimed to cure witchcraft-induced, AIDS-like illnesses. There is an urgent need for improved biomedical services, and TH interventions could be important in future HIV/AIDS education and care.
Acquired Immunodeficiency Syndrome↗
From trial intervention to scale-up: costs of an adolescent sexual health program in Mwanza, Tanzania.
OBJECTIVE: To estimate annual costs of a multifaceted adolescent sexual health intervention in Mwanza, Tanzania, by input (capital and recurrent), component (in-school, community activities, youth-friendly health services, condom distribution), and phase (development, startup, trial implementation, scale-up). STUDY DESIGN: Financial and economic providers' costs and intervention outputs were collected to estimate annual total and unit costs (1999-2001). The incremental financial budget projects funding requirements for scale-up within an integrated model. RESULTS: The 3-year economic costs of trial implementation were US dollars 879,032, of which approximately 70% were for the school-based component. Costs of initial development and startup were relatively substantial ( approximately 21% of total costs); however, annual costs per school child dropped from US dollars 16 in 1999 to US dollars 10 in 2001. The incremental scale-up cost is approximately 1/5 of ward trial implementation running costs. CONCLUSIONS: Annual costs can reduce by almost 40% as project implementation matures. When scaled up, only an additional US dollars 1.54 is needed per pupil per year to continue the intervention.
Adolescent↗
Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: Simulation results.
BACKGROUND AND OBJECTIVES: Population attributable fractions (PAF) from observational studies may under- or overestimate the contribution of cofactor sexually transmitted disease (STD) to human immunodeficiency virus (HIV) spread. Empirical PAF estimates from the Mwanza and Rakai trials indicated the proportion of HIV infections attributable to STDs was higher in Mwanza than Rakai. GOAL OF THIS STUDY: Estimate the "true" proportion (PAFM) of HIV infections attributable to STDs in the Mwanza and Rakai STD trial populations and explore how the evaluated interventions prevented HIV infections. STUDY DESIGN: The STDSIM model was used to simulate the 2 populations at the baseline of the trials (with no STD treatment interventions) and counterfactual scenarios in which STD cofactor effects on HIV spread were removed either at the start of the trials or 2, 10, and 20 years into the HIV epidemics. Similar methods were used to quantify the contribution of the cure of each STD to overall HIV impact in each site. RESULTS: : In Mwanza, the highest PAFM for the effect of any single STD over the 2 years of the trial was due to chancroid (40%). The PAFM for all curable STD was 65%. In Rakai, herpes simplex virus type 2 (HSV-2) was the most important STD (PAFM = 23%); the PAFM for curable STD was 20%. In both sites, the proportion of new infections due to treatable STD decreased over time. The decrease was greater for Rakai, where a behavioral risk reduction that preceded the trial reduced STD prevalence. In both sites, the importance of HSV-2 increased later in the HIV epidemics and STD increased transmission of HIV more than acquisition of HIV. In the Mwanza trial, treatment of chancroid contributed most to preventing new HIV infections. CONCLUSIONS: PAFs calculated from empirical data underestimated the contribution of STD to HIV spread in the Mwanza and Rakai trial populations because STD effects on HIV transmission (as opposed to acquisition) were not captured in the observationally based studies.
Computer Simulation↗
How important are unsafe medical injections in the spread of HIV in Africa?
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Africa↗
Farming with your hoe in a sack: condom attitudes, access, and use in rural Tanzania.
This study examines condom knowledge, attitudes, access, and practices in rural Mwanza, Tanzania. From 1999-2002, six researchers carried out participant observation in nine villagesfor a total of 158 person-weeks. Many villagers perceived condoms negatively for multiple reasons, for example, the method's association with infection or promiscuity, reduced male sexual pleasure, and cultural understandings of meaningful sex. Men controlled the terms of sexual encounters and reported that they would use condoms only with risky partners, but few perceived their partners as such. Use of condoms appeared to be very low, primarily as a result of limited demand, although barriers to access also existed. These qualitative findings contrast with inconsistent survey reports of relatively high condom use in the same population. Intervention efforts should address the tradeoff between possible short- and long-term consequences of condom use, particularly for men, for example, reduced pleasure versus reduced HIV risk. If possible, surveys should assess the validity of reported condom use through comparison with other data, including qualitative findings and distribution/sales records.
Adolescent↗
Uptake of workplace HIV counselling and testing: a cluster-randomised trial in Zimbabwe.
BACKGROUND: HIV counselling and testing is a key component of both HIV care and HIV prevention, but uptake is currently low. We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing (VCT). METHODS AND FINDINGS: The study was a cluster-randomised trial of two VCT strategies, with business occupational health clinics as the unit of randomisation. VCT was directly offered to all employees, followed by 2 y of open access to VCT and basic HIV care. Businesses were randomised to either on-site rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for off-site VCT at a chain of free-standing centres also using rapid tests (11 businesses). Baseline anonymised HIV serology was requested from all employees. HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on-site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532 employees taking vouchers at clinics randomised to off-site testing (mean uptake by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8 (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders. Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 (95% confidence interval 8.2 to 16.8). CONCLUSIONS: High-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa. VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care. Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT.
AIDS Serodiagnosis↗
Overview of effective and promising interventions to prevent HIV infection.
OBJECTIVE: To review the evidence for the effectiveness of a variety of approaches to preventing HIV infection. METHODS: We reviewed what is known about the efficacy and effectiveness of a range of prevention approaches that are at various stages of research. These interventions attempt to induce behavioural change, apply technologies or modify social environments. Our intention was not to provide an exhaustive review of all types of HIV prevention strategies but rather to illustrate the landscape of interventions that have been developed and evaluated in different settings and that have the potential for widespread application among both adults and young people. FINDINGS: There is a large quantity of evidence from experimental and observational research as well as from practical real-world experience in both developed and developing countries. This evidence supports the implementation and scale-up of a number of interventions and strategies. At the same time, there is a need to continue to develop new and more effective interventions while attending to a number of behavioural and social issues that cut across virtually all interventions designed to prevent the spread of HIV. CONCLUSION: We caution against confusing lack of implementation with lack of effectiveness and call for continual improvement in the quality and quantity of evidence. We have also identified a number of important directions for future HIV prevention research.
AIDS Vaccines↗
Is sexual contact with sex workers important in driving the HIV epidemic among men in rural Zimbabwe?
OBJECTIVE: To establish the importance of commercial sex in driving the HIV epidemic in the general population by determining risk factors for HIV infection among male mine and farm workers and estimating the fraction of prevalent HIV infections attributable to sexual contact with sex workers (SWs). SETTING: Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. METHODS: A cross-sectional interviewer-administered questionnaire and urine survey of 1405 male workers. Urine samples were tested for HIV antibodies by a particle agglutination test and enzyme-linked immunosorbent assay and for Chlamydia trachomatis and Neisseria gonorrhoeae using a polymerase chain reaction assay. RESULTS: The overall prevalence of HIV antibodies was 27.3% (95% confidence interval [CI]: 24.8 to 29.5), that of C. trachomatis was 1.5% (95% CI: 1.0 to 2.1), and that of N. gonorrhoeae was 0.5% (95% CI: 0.1 to 0.9). A total of 48.4% (95% CI: 45.8 to 51.0) of men reported ever having had sexual contact with an SW, and 29.3% (95% CI: 26.9 to 31.7) reported contact in the past year. HIV was more common among men who reported SW contact on univariate (1.9% [95% CI: 1.5 to 2.4]) and multivariate (1.4% [95% CI: 1.0 to 1.8]) analysis after adjusting for confounding. HIV was also strongly associated with self-reported genital ulceration in the previous 6 months (adjusted odds ratio [OR] = 3.1, 95% CI: 2.2 to 4.3). Genital ulceration and SW contact were highly correlated. A total of 19.6% of HIV infections in men could be attributed to ever having had sexual contact with an SW (95% CI: 10.8 to 27.6). CONCLUSIONS: An appreciable proportion of HIV infection in men is attributable to sexual contact with SWs. Consideration should be given to developing interventions that target male clients of SWs.
Adult↗
Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study.
CONTEXT: Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials, but implementation has been limited and there are no data on effectiveness under routine conditions. OBJECTIVE: To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions. DESIGN, SETTING, AND PARTICIPANTS: Randomized intervention study with a novel incremental recruitment design. Between 1999 and 2001 (before antiretroviral therapy was available), 1655 HIV-infected male employees of a South African gold-mining company (median age, 37 years) were enrolled in the study. Median follow-up was 22.1 months. INTERVENTION: Employees were invited in random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self-administered for 6 months among attendees with no evidence of active tuberculosis. MAIN OUTCOME MEASURE: Incidence of tuberculosis (including both first and recurrent episodes) during the periods before and after clinic enrollment. RESULTS: A total of 1016 of 1655 men included in the analysis attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men eligible to start primary isoniazid preventive therapy did so. The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years, respectively (incidence rate ratio [IRR] after adjustment for calendar period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable analysis adjusting for calendar period, age, and silicosis grade, the tuberculosis IRR for clinic enrollment was 0.62 (95% CI, 0.43-0.89). In a further analysis excluding individuals with a history of tuberculosis (and, hence, ineligible for isoniazid preventive therapy), the adjusted IRR for clinic enrollment was 0.54 (95% CI, 0.35-0.83). CONCLUSIONS: Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38% overall and by 46% among individuals with no history of tuberculosis prior to the study. Tuberculosis incidence remained high despite isoniazid preventive therapy, and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons.
AIDS-Related Opportunistic Infections↗
The appropriateness of core group interventions using presumptive periodic treatment among rural Zimbabwean women who exchange sex for gifts or money.
To map the characteristics of rural based sex workers in Zimbabwe with regard to demographics, mobility, behavior, HIV and sexually transmitted infection (STI) prevalence, to explore the appropriateness and feasibility of presumptive periodic treatment (PPT) for bacterial STIs as an HIV prevention intervention among these women, and to compare tolerability of 2 PPT regimens (1 g of azithromycin and 2 g of metronidazole+/-500 mg of ciprofloxacin). Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. Three hundred sixty-three sex workers were recruited and completed a structured interviewer-administered questionnaire. Each participant had blood tested for antibody to HIV, herpes simplex virus 2 (HSV-2), and syphilis; urine tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and a vaginal swab tested for Trichomonas vaginalis (TV). Women were randomly assigned to receive a single dose of 1 of 2 PPT regimens and then followed to assess rates of side effects and reinfection. The overall prevalence of antibody to HIV was 55.7% (95% confidence interval [CI]: 50.6-60.9) and that of HSV-2 was 80.8% (95% CI: 76.7-84.9). The prevalence of CT and NG was low (CT=1.7%, 95% CI: 0.3-3.0); (NG=1.9%, 95% CI: 0.5-3.4), with a much higher prevalence of TV (TV=19.3%, 95% CI: 15.2-23.4). Prevalence of CT, NG, and TV was appreciably reduced 1 month after PPT but rose to pretreatment levels at the 2- and 3-month visits. The rate of moderate or severe side effects after PPT was low, but it was higher in the women who received ciprofloxacin in addition to azithromycin and metronidazole (P=0.007). It was feasible to access women who reported exchanging money or gifts for sex in rural communities, although many of these women engaged in sex work only infrequently. The prevalence of bacterial STIs was low, suggesting that PPT may not be an appropriate intervention in this setting. Rapid reinfection after PPT suggests that this needs to be given at monthly intervals to reduce prevalence of STIs.
Adult↗
The MEMA kwa Vijana project: design of a community randomised trial of an innovative adolescent sexual health intervention in rural Tanzania.
BACKGROUND: Effective interventions to reduce the incidence of HIV, other sexually transmitted infections (STIs) and unwanted pregnancy among adolescents in sub-Saharan Africa are urgently needed. This paper describes the rationale and design of a randomised trial of the impact of an innovative sexual health intervention among adolescents in rural Mwanza Region, Tanzania. METHODS: The MEMA kwa Vijana intervention comprises a teacher-led, peer-assisted sexual health education programme for students in the last 3 years of primary school, training and supervision of health workers in the provision of youth-friendly health services, peer condom promotion and distribution, and wider community activities. Detailed process evaluation was conducted and the impact of the intervention was evaluated through a community-randomised trial in which a cohort of 9645 adolescents was followed up for 3 years. Both process and impact evaluation used multiple assessment methods. Impact measures included incidence and prevalence of HIV and other STIs, pregnancy rates, knowledge and reported attitudes and sexual behaviour, as well as qualitative assessments. RESULTS: Results of the baseline survey of the cohort have been presented previously. The outcome of the trial will be reported separately. CONCLUSIONS: Behaviour change interventions among adolescents have been widely advocated, but there have been few rigorously designed trials of their effectiveness, particularly in developing countries, and measurement of sexual behaviour is particularly problematic in this age group. The MEMA kwa Vijana trial was undertaken to address these problems and to collect rigorous evidence on the effectiveness of an innovative intervention, designed to be implemented on a very large scale.
Adolescent↗
Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study.
OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.
Adolescent↗
Does tuberculosis increase HIV load?
BACKGROUND: The effect that tuberculosis (TB) has on human immunodeficiency virus (HIV) disease progression is not clearly understood. METHODS: In an observational cohort study of HIV-infected adults in South Africa, baseline and final HIV load were compared between individuals who experienced an episode of TB (n=30) during follow-up and control subjects (n=56) matched by baseline CD4 cell count and follow-up time; linear regression modeling was used to control for confounding. RESULTS: Mean HIV load was higher in the TB group than in the non-TB control group for both baseline (4.73 vs. 4.24 log(10) copies/mL; P=.003) and final values (5.02 vs. 4.34 log(10) copies/mL; P<.001). After adjustment for baseline HIV load and World Health Organization HIV stage, the difference in final HIV load was 0.24 log(10) copies/mL (95% confidence interval, -0.01 to 0.50 log(10) copies/mL; P=.06). CONCLUSIONS: Poor prognosis for HIV-infected individuals after TB may be due to preexisting high HIV load rather than to the TB event itself. An episode of TB was associated with a small adjusted increase in HIV load at the end of the study--an increase that would not be regarded as clinically significant in an individual but could have some effect on HIV disease progression or HIV transmission at the population level. Prevention of TB is important for the reduction of HIV-related morbidity and mortality; however, antiretroviral therapy is required to have a major effect on survival in individuals with HIV disease.
AIDS-Related Opportunistic Infections↗
Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners.
We hypothesized that rapid presentation may be a general feature of tuberculosis (TB) associated with human immunodeficiency virus (HIV) that limits the impact of HIV on the point prevalence of TB. To investigate this, we performed a cross-sectional HIV and TB disease survey with retrospective and prospective follow-up. HIV prevalence among 1,773 systematically recruited miners was 27%. TB incidence was much more strongly HIV associated (incidence rate ratio, 5.5; 95% confidence interval [CI], 3.5-8.6) than the point prevalence of undiagnosed TB disease (odds ratio, 1.7; 95% CI, 0.9-3.3). For smear-positive TB, 7 of 9 (78%) prevalent cases were HIV negative, and point prevalence was nonsignificantly lower in miners who were HIV positive (odds ratio, 0.8; 95% CI, 0.1-4.2). The calculated mean duration of smear positivity before diagnosis (point prevalence/incidence) was substantially shorter for HIV-positive than HIV-negative TB patients (0.17 and 1.15 years, respectively; ratio, 0.15; 95% CI, 0.00-0.73). HIV has considerably less impact on the point prevalence of TB disease than on TB incidence, probably because rapid disease progression increases presentation and case-finding rates. The difference in mean duration of smear positivity was particularly marked and, if generalizable, will have major implications for TB control prospects in high HIV prevalence areas.
Adolescent↗
Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections.
During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1.
Adolescent↗