Geoff P. Garnett

The Impact of Migration on HIV-1 Transmission in South Africa: A Study of Migrant and Nonmigrant Men and Their Partners

Background To investigate the association between migration and HIV infection among migrant and nonmigrant men and their rural partners. Goal The goal was to determine risk factors for HIV-1 infection in South Africa. Study Design This was a cross-sectional study of 196 migrant men and 130 of their rural partners, as well as 64 nonmigrant men and 98 rural women whose partners are nonmigrant. Male migrants were recruited at work in two urban centers, 100 km and 700 km from their rural homes. Rural partners were traced and invited to participate. Nonmigrant couples were recruited for comparison. The study involved administration of a detailed questionnaire and blood collection for HIV testing. Results Testing showed that 25.9% of migrant men and 12.7% of nonmigrant men were infected with HIV (P = 0.029; odds ratio = 2.4; 95% CI = 1.1–5.3). In multivariate analysis, main risk factors for male HIV infection were being a migrant, ever having used a condom, and having lived in four or more places during a lifetime. Being the partner of a migrant was not a significant risk factor for HIV infection among women; significant risk factors were reporting more than one current regular partner, being younger than 35 years, and having STD symptoms during the previous 4 months. Conclusion Migration is an independent risk factor for HIV infection among men. Workplace interventions are urgently needed to prevent further infections. High rates of HIV were found among rural women, and the migration status of the regular partner was not a major risk factor for HIV. Rural women lack access to appropriate prevention interventions, regardless of their partners’ migration status.

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.

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.

The theoretical population-level impact of a prophylactic human papilloma virus vaccine

Background. The ongoing development of a vaccine against human papillomavirus (HPV) raises important questions about the impact of various vaccination strategies. Methods. Two mathematical models are developed to explore the population-level impact of an HPV vaccine. The first model focuses on the infection process and the second on the disease process (specifically, cervical carcinoma in situ and cancer). Results. Both population characteristics (ie, sexual mixing and rates of sex partner change) and vaccine characteristics affect the steady state prevalence of HPV that would be expected if a vaccine program is implemented. Under a particular set of assumptions, we find that vaccinating both men and women against a specific HPV type would result in a 44% decrease in prevalence of that type whereas vaccinating only women would result in a 30% reduction. We also find that if a vaccine gives protection against some, but not all, high risk types of HPV, the reduction in disease may be less than the reduction in HPV because the remaining high risk HPV types may replace the disease caused by the eliminated types. Conclusions. A multivalent vaccine containing the majority of disease-causing HPV types would greatly reduce the need for colposcopy, biopsy and treatment. However, it is unlikely that Pap-screening programs would become redundant unless the vaccine is highly effective and coverage is widespread. In contrast to less common infections that are primarily restricted to core groups, targeting the vaccine towards the most sexually active individuals is less effective for a common sexually transmitted infection such as HPV.

The role of sexual partnership networks in the epidemiology of gonorrhea.

Background: Empirical studies have the potential to collect data on patterns of sexual mixing and network structures. Goal: To explore the contribution of different network measures in sexually transmitted disease epidemiology. Study Design: Individual‐based stochastic simulations of a network of sexual partnerships and sexually transmitted disease transmission are analyzed using logistic regression. Results and Conclusions: Measures accumulated over times similar to the duration of infection are more informative than are static cross sections. The patterns of sexual mixing and network structure influence patterns of infection. In particular, the establishment of infection is most sensitive to the proportion of nonmonogamous pairs, the component distribution and cohesion among those with high activity. The subsequent prevalence is most sensitive to the assortativeness of mixing in the high‐activity class and a measure of cohesion, both of which reflect the decrease in prevalence brought about by less widespread connections. A persons risk for infection is determined by local rather than global network structures.

Examining the promise of HIV elimination by 'test and treat' in hyperendemic settings.

Background:It has been suggested that a new strategy for HIV prevention, ‘Universal Test and Treat’, whereby everyone is tested for HIV once a year and treated immediately with antiretroviral therapy (ART) if they are infected, could ‘eliminate’ the epidemic and reduce ART costs in the long term. Methods:We investigated the impact of test-and-treat interventions under a variety of assumptions about the epidemic using a deterministic mathematical model. Results:Our model shows that such an intervention can substantially reduce HIV transmission, but that impact depends crucially on the epidemiological context; in some situations, less aggressive interventions achieve the same results, whereas in others, the proposed intervention reduces HIV by much less. It follows that testing every year and treating immediately is not necessarily the most cost-efficient strategy. We also show that a test-and-treat intervention that does not reach full implementation or coverage could, perversely, increase long-term ART costs. Conclusion:Interventions that prevent new infections through ART scale-up may hold substantial promise. However, as plans move forward, careful consideration should be given to the nature of the epidemic and the potential for perverse outcomes.

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.

Can we reverse the HIV/AIDS pandemic with an expanded response?

HIV/AIDS has reached pandemic proportions, and is one of the leading causes of death worldwide. In 2001, the Declaration of Commitment on HIV/AIDS set out several aims with respect to reducing the effect and spread of HIV/AIDS, and an expanded response in low-income and middle-income countries was initiated. Here we examine the potential effect of the expanded global response based on analyses of epidemiological data, of mathematical models of HIV-1 transmission, and a review of the impact of prevention interventions on risk behaviours. Analyses suggest that if the successes achieved in some countries in prevention of transmission can be expanded to a global scale by 2005, about 29 million new infections could be prevented by 2010.

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.

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.