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Biomedical subjects

Geoff P Garnett

Publications and source records attributed to Geoff P Garnett.

At least 19 recordsLinked to original sources
PubMed2007

Appropriate evaluation of HIV prevention interventions: from experiment to full-scale implementation.

BACKGROUND: Preventing HIV infection is still an essential goal in tackling the HIV/AIDS pandemic. Remarkably little is known about how best to reduce HIV incidence because most trials focus on the reduction of risk behaviours and assume an effect on HIV incidence. OBJECTIVE: To discuss the evidence for the effectiveness of HIV prevention strategies, exploring the different types of evidence available: individual and community randomised controlled trials, and observational studies. RESULTS: Although providing a gold standard for evidence, trials have been limited in their scope and are difficult to interpret and generalize. There have been examples of national level successes in preventing HIV which have been detected in surveillance data and understood through behavioural and modelling studies. These have the advantage of being to scale and indicating effectiveness rather than efficacy. CONCLUSIONS: Although randomised trials are important because of their scientific rigor, it is also important that evidence from observational epidemiology is not overlooked. Only if good quality, consistent data are available can the history of the HIV epidemic be appropriately analysed.

HIV Infections↗
PubMed2006

The role of sexually transmitted infections in male circumcision effectiveness against HIV--insights from clinical trial simulation.

BACKGROUND: A landmark randomised trial of male circumcision (MC) in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting MC effectiveness of 61% (95% CI: 34%-77%). Additionally, two further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently stopped early to report 53% and 48% effectiveness, respectively. Since MC may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness. OBJECTIVES AND METHODS: Focusing on the MC trial in Kisumu, we used a stochastic prevention trial simulator (1) to determine whether statistical analyses can validly estimate efficacy, (2) to determine whether MC efficacy against STI alone can produce large effectiveness against HIV and (3) to estimate the fraction of all HIV infections prevented that are attributable to efficacy against STI when both efficacies combine. RESULTS: Valid estimation of separate efficacies against HIV and STI as well as MC effectiveness is feasible with available STI and HIV trial data, under Kisumu trial conditions. Under our parameter assumptions, high overall effectiveness of MC against HIV was observed only with a high MC efficacy against HIV and was not possible on the basis of MC efficacy against STI alone. The fraction of all HIV infections prevented which were attributable to MC efficacy against STI was small, except when efficacy of MC specifically against HIV was very low. In the three MC trials which reported between 48% and 61% effectiveness (combining STI and HIV efficacies), the fraction of HIV infections prevented in circumcised males which were attributable to STI was unlikely to be more than 10% to 20%. CONCLUSION: Estimation of efficacy, attributable fraction and effectiveness leads to improved understanding of trial results, gives trial results greater external validity and is essential to determine the broader public health impact of circumcision to men and women.

Journal Article↗
PubMed2006

Is HIV out of control in the UK? An example of analysing patterns of HIV spreading using incidence-to-prevalence ratios.

The incidence of diagnosed HIV in the UK is increasing. We calculated the incidence-to-prevalence ratio, IPR(t), which must exceed an 'epidemic threshold', the reciprocal of the mean infectious period, for sustained transmission to occur. For heterosexuals the IPR(t) is too low for a self-sustained UK epidemic, and incidence is driven by increasing prevalence, mostly from imported cases. For men who have sex with men the IPR(t) is around the epidemic threshold, suggesting that spread is not yet under control.

Disease Outbreaks↗
PubMed2006

Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

BACKGROUND: Candidate human papillomavirus (HPV) vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation) and high (90% in a national immunisation programme) coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16) cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to significantly decrease HPV type-specific cervical cancer incidence. High vaccine coverage of women alone, sustained over many decades, with a long duration of vaccine-conferred protection, would have the greatest impact on type-specific cancer incidence. This level of coverage could be achieved through national coordinated programmes, with surveillance to detect cancers caused by nonvaccine oncogenic HPV types.

Female↗
PubMed2006

Assessing adult mortality in HIV-1-afflicted Zimbabwe (1998 -2003).

OBJECTIVE: To compare alternative methods to vital registration systems for estimating adult mortality, and describe patterns of mortality in Manicaland, Zimbabwe, which has been severely affected by HIV. METHODS: We compared estimates of adult mortality from (1) a single question on household mortality, (2) repeated household censuses, and (3) an adult cohort study with linked HIV testing from Manicaland, with a mathematical model fitted to local age-specific HIV prevalence (1998 -2000). FINDINGS: The crude death rate from the single question (29 per 1000 person-years) was roughly consistent with that from the mathematical model (22 -25 per 1000 person-years), but much higher than that from the household censuses (12 per 1000 person-years). Adult mortality in the household censuses (males 0.65; females 0.51) was lower than in the cohort study (males 0.77; females 0.57), while mathematical models gave a much higher estimate, especially for females (males 0.80 -0.83; females 0.75 -0.80). The population attributable fraction of adult deaths due to HIV was 0.61 for men and 0.70 for women, with life expectancy estimated to be 34.3 years for males and 38.2 years for females. CONCLUSION: Each method for estimating adult mortality had limitations in terms of loss to follow-up (cohort study), under-ascertainment (household censuses), transparency of underlying processes (single question), and sensitivity to parameterization (mathematical model). However, these analyses make clear the advantages of longitudinal cohort data, which provide more complete ascertainment than household censuses, highlight possible inaccuracies in model assumptions, and allow direct quantification of the impact of HIV.

Adult↗
PubMed2006

Modelling the impact of antiretroviral use in resource-poor settings.

BACKGROUND: The anticipated scale-up of antiretroviral therapy (ART) in high-prevalence, resource-constrained settings requires operational research to guide policy on the design of treatment programmes. Mathematical models can explore the potential impacts of various treatment strategies, including timing of treatment initiation and provision of laboratory monitoring facilities, to complement evidence from pilot programmes. METHODS AND FINDINGS: A deterministic model of HIV transmission incorporating ART and stratifying infection progression into stages was constructed. The impact of ART was evaluated for various scenarios and treatment strategies, with different levels of coverage, patient eligibility, and other parameter values. These strategies included the provision of laboratory facilities that perform CD4 counts and viral load testing, and the timing of the stage of infection at which treatment is initiated. In our analysis, unlimited ART provision initiated at late-stage infection (AIDS) increased prevalence of HIV infection. The effect of additionally treating pre-AIDS patients depended on the behaviour change of treated patients. Different coverage levels for ART do not affect benefits such as life-years gained per person-year of treatment and have minimal effect on infections averted when treating AIDS patients only. Scaling up treatment of pre-AIDS patients resulted in more infections being averted per person-year of treatment, but the absolute number of infections averted remained small. As coverage increased in the models, the emergence and risk of spread of drug resistance increased. Withdrawal of failing treatment (clinical resurgence of symptoms), immunologic (CD4 count decline), or virologic failure (viral rebound) increased the number of infected individuals who could benefit from ART, but effectiveness per person is compromised. Only withdrawal at a very early stage of treatment failure, soon after viral rebound, would have a substantial impact on emergence of drug resistance. CONCLUSIONS: Our analysis found that ART cannot be seen as a direct transmission prevention measure, regardless of the degree of coverage. Counselling of patients to promote safe sexual practices is essential and must aim to effect long-term change. The chief aims of an ART programme, such as maximised number of patients treated or optimised treatment per patient, will determine which treatment strategy is most effective.

Anti-Retroviral Agents↗
PubMed2006

Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment.

Adolescent↗
PubMed2006

The global impact of scaling up HIV/AIDS prevention programs in low- and middle-income countries.

A strong, global commitment to expanded prevention programs targeted at sexual transmission and transmission among injecting drug users, started now, could avert 28 million new HIV infections between 2005 and 2015. This figure is more than half of the new infections that might otherwise occur during that period in 125 low- and middle-income countries. Although preventing these new infections would require investing about U.S.$122 billion over this period, it would reduce future needs for treatment and care. Our analysis suggests that it will cost about U.S.$3900 to prevent each new infection, but that this will produce a savings of U.S.$4700 in forgone treatment and care costs. Thus, greater spending on prevention now would not only prevent more than half the new infections that would occur from 2005 to 2015 but would actually produce a net financial saving as future costs for treatment and care are averted.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Creating and validating an algorithm to measure AIDS mortality in the adult population using verbal autopsy.

BACKGROUND: Vital registration and cause of death reporting is incomplete in the countries in which the HIV epidemic is most severe. A reliable tool that is independent of HIV status is needed for measuring the frequency of AIDS deaths and ultimately the impact of antiretroviral therapy on mortality. METHODS AND FINDINGS: A verbal autopsy questionnaire was administered to caregivers of 381 adults of known HIV status who died between 1998 and 2003 in Manicaland, eastern Zimbabwe. Individuals who were HIV positive and did not die in an accident or during childbirth (74%; n = 282) were considered to have died of AIDS in the gold standard. Verbal autopsies were randomly allocated to a training dataset (n = 279) to generate classification criteria or a test dataset (n = 102) to verify criteria. A rule-based algorithm created to minimise false positives had a specificity of 66% and a sensitivity of 76%. Eight predictors (weight loss, wasting, jaundice, herpes zoster, presence of abscesses or sores, oral candidiasis, acute respiratory tract infections, and vaginal tumours) were included in the algorithm. In the test dataset of verbal autopsies, 69% of deaths were correctly classified as AIDS/non-AIDS, and it was not necessary to invoke a differential diagnosis of tuberculosis. Presence of any one of these criteria gave a post-test probability of AIDS death of 0.84. CONCLUSIONS: Analysis of verbal autopsy data in this rural Zimbabwean population revealed a distinct pattern of signs and symptoms associated with AIDS mortality. Using these signs and symptoms, demographic surveillance data on AIDS deaths may allow for the estimation of AIDS mortality and even HIV prevalence.

Adolescent↗
PubMed2005

The epidemiological impact of antiretroviral use predicted by mathematical models: a review.

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.

Journal Article↗
PubMed2005

Vicious and virtuous circles in the dynamics of infectious disease and the provision of health care: gonorrhea in Britain as an example.

Prompt treatment of infectious diseases plays an important role in infection control. In the face of the increasing incidence of sexually transmitted infection, the ability of genitourinary medicine services to provide appropriate and timely care is reduced. To explore the relationship between capacity and demand for care, we developed and analyzed a mathematical model of gonorrhea transmission, incorporating patient flow through treatment services and heterogeneity in sexual risk behavior. Two equilibrium levels of infection incidence--"high" and "low"--exist for the same parameter values, and which of them occurs depends on starting conditions. At the high-incidence equilibrium, there is a "vicious circle" in which inadequate treatment capacity leads to many untreated infections, generating further high incidence and high demand and thus maintaining the inadequacy of services. A substantial increase in capacity is needed to interrupt this process and enter a "virtuous circle," in which adequate service provision keeps demand low, offering cost savings as well as improvements in health.

Adolescent↗
PubMed2005

Individual level injection history: a lack of association with HIV incidence in rural Zimbabwe.

BACKGROUND: It has recently been argued that unsafe medical injections are a major transmission route of HIV infection in the generalised epidemics of sub-Saharan Africa. METHODS AND FINDINGS: We have analysed the pattern of injections in relation to HIV incidence in a population cohort in Manicaland in a rural area of Zimbabwe. In Poisson regression models, injections were not found to be associated with HIV in males (rate ratio = 0.33; 95% confidence interval: 0.07 to 1.46) or females (rate ratio = 1.04; 95% confidence interval: 0.59 to 1.85). CONCLUSION: It is important that unsafe medical injections can be confidently excluded as a major source of HIV infection. In rural Zimbabwe the evidence is that they can.

Adolescent↗
PubMed2004

Estimating the global burden of HIV/AIDS: what do we really know about the HIV pandemic?

The validity of UNAIDS/WHO estimates of the burden of HIV/AIDS is rightly questioned by politicians, scientists, and activists-especially since the 2003 estimates to be released in July, 2004, will show substantial drops in the burden of HIV/AIDS in several countries, and increases in others. However, the estimates are based on an explicit attempt to meet criteria we believe should guide the generation of international morbidity and mortality figures. These criteria extend beyond the quality of the input data to include features of the estimation process such as transparency and participation. The 2003 estimates now include plausible ranges for estimates rather than a single best estimate. This reduces the chance that insignificant differences in estimates from different sources are given importance. Here, we describe the levels of uncertainty associated with the UNAIDS/WHO estimates of HIV/AIDS. We explain the reason for moving to the use of plausibility bounds, the factors that determine the width of the bounds, and the implications for policy makers and programme managers.

Acquired Immunodeficiency Syndrome↗
PubMed2004

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↗
PubMed2004

Scale-free networks and sexually transmitted diseases: a description of observed patterns of sexual contacts in Britain and Zimbabwe.

BACKGROUND: Sexually transmitted infections spread through a network of contacts created by the formation of sexual partnerships. In physics, networks have been characterized as "scale-free" if they follow a power law with an exponent between 2 and 3. OBJECTIVE: The objective of this study was to test statistically whether distributions of numbers of sexual partners reported from different populations are well described by power laws. STUDY DESIGN: Power laws and an exponential null model are fitted by maximum likelihood techniques to reported distributions of numbers of partners. Data are taken from 4 population-based surveys, 3 from Britain and 1 from rural Zimbabwe. RESULTS: The networks can be described by power laws over a number of orders of magnitude. In addition, the derived exponents differ significantly and meaningfully, with an "accelerating network" formed between men who have sex with men (MSM). CONCLUSIONS: A scale-free network approach provides a reasonable description of distributions of reported numbers of sexual partners.

Adolescent↗
PubMed2003

Who infects whom? HIV-1 concordance and discordance among migrant and non-migrant couples in South Africa.

OBJECTIVES: To measure HIV-1 discordance among migrant and non-migrant men and their rural partners, and to estimate the relative risk of infection from inside versus outside primary relationships. DESIGN: A cross-sectional behavioural and HIV-1 seroprevalence survey among 168 couples in which the male partner either a migrant, or not. METHODS: A detailed questionnaire was administered and blood was collected for laboratory analysis. A mathematical model was developed to estimate the relative risk of infection from inside versus from outside regular relationships. RESULTS: A total of 70% (117 of 168) of couples were negatively concordant for HIV, 9% (16 of 168) were positively concordant and 21% (35 of 168) were discordant. Migrant couples were more likely than non-migrant couples to have one or both partners infected [35 versus 19%; P = 0.026; odds ratio (OR) = 2.28] and to be HIV-1 discordant (27 versus 15%; P = 0.066; OR = 2.06). In 71.4% of discordant couples, the male was the infected partner; this did not differ by migration status. In the mathematical model, migrant men were 26 times more likely to be infected from outside their regular relationships than from inside [relative risk (RR) = 26.3; P = 0.000]; non-migrant men were 10 times more likely to be infected from outside their regular relationships than inside (RR = 10.5; P = 0.00003). CONCLUSIONS: Migration continues to play an important role in the spread of HIV-1 in South Africa. The direction of spread of the epidemic is not only from returning migrant men to their rural partners, but also from women to their migrant partners. Prevention efforts will need to target both migrant men and women who remain at home.

Adult↗