Peter Piot

Non-Ulcerative Sexually Transmitted Diseases as Risk Factors for HIV-1 Transmission in Women: Results From a Cohort Study

OBJECTIVES The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world. The transmission probability of HIV-1 per sexual contact is low, but may be greatly enhanced by several cofactors. Sexually transmitted diseases (STD), especially genital ulcers, may be such factors. So far, epidemiological evidence that other STD facilitate HIV-1 transmission is weak. The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. METHODS We conducted a nested case-control study of 431 initially HIV-1-negative women followed prospectively for a mean duration of 2 years (with monthly STD check-ups and 3-monthly HIV-1 serology). Cases (seroconverters, n = 68) were compared with controls (women who remained HIV-1-negative, n = 126) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. RESULTS The annual incidence of HIV-1 in this cohort was 9.8%. Seroconverters were younger than HIV-1-negative women (mean age, 24.6 versus 26.8 years; P = 0.04). During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhoea, chlamydial infection and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratios for seroconversion were 4.8 [95% confidence interval (CI), 2.4-9.8] for gonorrhoea, 3.6 (95% CI, 1.4-9.1) for chlamydial infection and 1.9 (95% CI, 0.9-4.1) for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. CONCLUSION Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women, after controlling for sexual exposure. Because of their high prevalence in some populations, non-ulcerative STD may represent a considerable population-attributable risk in the transmission of HIV-1 worldwide. The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS.

Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US

Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men

9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.

ACQUIRED IMMUNODEFICIENCY SYNDROME IN A HETEROSEXUAL POPULATION IN ZAIRE

To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 (HIV-1), a prospective study was carried out in 422 men who had acquired a sexually transmitted disease (STD) from a group of prostitutes with a prevalence of HIV-1 infection of 85%. The initial seroprevalence of HIV among the men was 12%. 24 of 293 (8.2%) initially seronegative men seroconverted to HIV-1. Newly acquired infection was independently associated with frequent prostitute contact (risk ratio 3.2, 95% confidence interval 1.2-8.1), with the acquisition of genital ulcer disease (risk ratio 4.7, 95% confidence interval 1.3-17.0), and with being uncircumcised (risk ratio 8.2, 95% confidence interval 3.0-23.0). 96% of documented seroconversions occurred in men with one or both of the latter two risk factors. In a subgroup of 73 seronegative men who reported a single prostitute sexual contact, the frequency of HIV-1 infection was 8.2% during 12 weeks of observation. No man without a genital ulcer seroconverted. A cumulative 43% of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure. These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision, genital ulcer disease, and susceptibility to HIV-1 infection.

Expansion of cancer care and control in countries of low and middle income: a call to action

38 patients with the acquired immunodeficiency syndrome (AIDS) were identified in Kinshasa, Zaire, during a 3 week period in 1983. The male to female ratio was 1.1:1. The annual case rate for Kinshasa was estimated to be at least 17 per 100 000. Opportunistic infections were diagnosed in 32 (84%) patients, disseminated Kaposis sarcoma (KS) with opportunistic infection in 5 (13%), and disseminated KS alone in 1 patient. Immunological characteristics of these patients were as reported for cases in the USA and Europe, but immunological abnormalities were also found in 6 controls with infectious diseases but no symptoms of AIDS. Female AIDS cases were younger than male patients with AIDS (mean ages 28.4 vs 41.1 years, respectively), and were more often single (14/18 vs 2/20). Homosexuality, intravenous drug abuse, and blood transfusion did not appear to be risk factors in these patients. The findings of this study strongly argue that the situation in central Africa represents a new epidemiological setting for this worldwide disease--that of significant transmission in a large heterosexual population. Two instances of clusters of AIDS (not included in the above series) involving males and females with frequent heterosexual contact further implicate heterosexual transmission.

Perinatal Transmission of the Human Immunodeficiency Virus Type 1 to Infants of Seropositive Women in Zaire

Substantial inequalities exist in cancer survival rates across countries. In addition to prevention of new cancers by reduction of risk factors, strategies are needed to close the gap between developed and developing countries in cancer survival and the effects of the disease on human suffering. We challenge the public health communitys assumption that cancers will remain untreated in poor countries, and note the analogy to similarly unfounded arguments from more than a decade ago against provision of HIV treatment. In resource-constrained countries without specialised services, experience has shown that much can be done to prevent and treat cancer by deployment of primary and secondary caregivers, use of off-patent drugs, and application of regional and global mechanisms for financing and procurement. Furthermore, several middle-income countries have included cancer treatment in national health insurance coverage with a focus on people living in poverty. These strategies can reduce costs, increase access to health services, and strengthen health systems to meet the challenge of cancer and other diseases. In 2009, we formed the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries, which is composed of leaders from the global health and cancer care communities, and is dedicated to proposal, implementation, and evaluation of strategies to advance this agenda.

Condom promotion, sexually transmitted diseases treatment, and declining incidence of HIV-1 infection in female Zairian sex workers

To examine perinatal transmission of the human immunodeficiency virus type 1 (HIV-1) in Zaire, we screened 8108 women who gave birth at one of two Kinshasa hospitals that serve populations of markedly different socioeconomic status. For up to one year, we followed the 475 infants of the 466 seropositive women (5.8 percent of those screened) and the 616 infants of 606 seronegative women matched for age, parity, and hospital. On the basis of clinical criteria, 85 of the seropositive women (18 percent) had the acquired immunodeficiency syndrome (AIDS). The infants of seropositive mothers, as compared with those of seronegative mothers, were more frequently premature, had lower birth weights, and had a higher death rate in the first 28 days (6.2 vs. 1.2 percent; P less than 0.0001). The patterns were similar at the two hospitals. Twenty-one percent of the cultures for HIV-1 of 92 randomly selected cord-blood samples from infants of seropositive women were positive. T4-cell counts were performed in 37 seropositive women, and cord blood from their infants was cultured. The cultures were positive in the infants of 6 of the 18 women with antepartum T4 counts of 400 or fewer cells per cubic millimeter, as compared with none of the infants of the 19 women with more than 400 T4 cells per cubic millimeter (P = 0.02). One year later, 21 percent of the infants of the seropositive mothers had died as compared with 3.8 percent of the control infants (P less than 0.001), and 7.9 percent of their surviving infants had AIDS. We conclude that the mortality rates among children of seropositive mothers are high regardless of socioeconomic status, and that perinatal transmission of HIV-1 has a major adverse effect on infant survival in Kinshasa.

AIDS virus infection in Nairobi prostitutes: spread of the epidemic to East Africa

The control of sexually transmitted diseases, including HIV-1, among sex workers and their clients in urban areas in developing countries, is considered a valuable and cost-effective intervention to contain the spread of HIV-1. The effect of a programme of STD treatment combined with condom promotion on HIV-1 incidence has so far not been measured. During an intervention including condom promotion, as well as monthly sexually transmitted disease screening and treatment among 531 initially HIV-1 negative female sex workers in Kinshasa, Zaire, 70 became infected with HIV-1 (incidence of 8.0 per 100 women-years [wy]). A decline of HIV-1 incidence was observed over time, from 11.7/100 wy during the first 6 months, to 4.4/100 wy over the last 6 months, 3 years later (p = 0.003). Simultaneously, regular use of condoms with clients went up from 11% to 52% and 68%, after 6 and 36 months of intervention, respectively. Risk factors for HIV-1 seroconversion after multivariate analysis included irregular condom use (RR 1.6 [95% Cl 1.1-2.8]), gonorrhoea (RR 2.5 [1.1-6.4]), trichomoniasis (RR 1.7 [1.1-2.8]), and genital ulcer disease (RR 2.5 [1.1-6.4]), during the probable period of acquisition of HIV-1. In women who attended more than 90% of their clinic appointments, the HIV-1 incidence was 2.7/100 wy compared to 7.1, 20.3, and 44.1 per 100 wy among women who attended 76-90%, 50-75%, and less than 50% of the monthly appointments, respectively (p < 0.0001). These trends remained after controlling for reported condom use and number of clients. This study confirms earlier findings that STDs facilitate transmission of HIV-1 and shows that a clinic-based intervention consisting of STD care and condom promotion can result in a major decline of HIV-1 incidence among female sex workers.

The global impact of HIV/AIDS

The acquired immunodeficiency syndrome (AIDS) is epidemic in Central Africa. To determine the prevalence of AIDS virus infection in East Africa, we studied 90 female prostitutes, 40 men treated at a clinic for sexually transmitted diseases, and 42 medical personnel in Nairobi, Kenya. Antibody to human T-cell lymphotropic virus Type III (HTLV-III) was detected in the serum of 66 percent of prostitutes of low socioeconomic status, 31 percent of prostitutes of higher socioeconomic status, 8 percent of the clinic patients, and 2 percent of the medical personnel. The presence of the antibody was associated with both immunologic and clinical abnormalities. The mean T-cell helper/suppressor ratio was 0.92 in seropositive prostitutes and 1.82 in seronegative prostitutes (P less than 0.0001). Generalized lymphadenopathy was present in 54 percent of seropositive prostitutes and 10 percent of seronegative prostitutes (P less than 0.0001). No constitutional symptoms, opportunistic infections, or cases of Kaposis sarcoma were present. Our results indicate that the epidemic of AIDS virus infection has, unfortunately, spread extensively among urban prostitutes in Nairobi, Kenya. Sexual exposure to men from Central Africa was significantly associated with HTLV-III antibody among prostitutes, suggesting transcontinental spread of the epidemic.

Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa

The scale of the human immunodeficiency virus (HIV)/AIDS epidemic has exceeded all expectations since its identification 20 years ago. Globally, an estimated 36 million people are currently living with HIV, and some 20 million people have already died, with the worst of the epidemic centred on sub-Saharan Africa. But just as the spread of HIV has been greater than predicted, so too has been its impact on social capital, population structure and economic growth. Responding to AIDS on a scale commensurate with the epidemic is a global imperative, and the tools for an effective response are known. Nothing less than a sustained social mobilization is necessary to combat one of the most serious crises facing human development.