Kevin M. De Cock

Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model

BACKGROUND Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6.7 million were still in need of treatment and a further 2.7 million became infected with HIV in 2007. Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination. METHODS We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive. We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual. FINDINGS The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years. It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial

1.7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease. INTERPRETATION Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics. This approach merits further mathematical modelling, research, and broad consultation.

Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment

BACKGROUND There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjans four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

Shadow on the continent: public health and HIV/AIDS in Africa in the 21st century.

Rapid scale-up of antiretroviral treatment programmes is happening in Africa, driven by international advocacy and policy directives and supported by unprecedented donor funding and technical assistance. This welcome development offers hope to millions of HIV-infected Africans, among whom tuberculosis is the major cause of serious illness and death. Little in the way of HIV diagnosis or care was previously offered to patients with tuberculosis, by either national tuberculosis or AIDS control programmes, with tuberculosis services focused exclusively on diagnosis and treatment of rising numbers of patients. Tuberculosis control in Africa has yet to adapt to the new climate of antiretroviral availability. Many barriers exist, from drug interactions to historic differences in the way that tuberculosis and HIV are perceived, but failure to successfully integrate HIV and tuberculosis control will threaten the viability of both programmes. Here, we review tuberculosis epidemiology in Africa and policy implications of HIV/AIDS treatment scale-up.

Molecular Evidence of Sexual Transmission of Ebola Virus

Approaches to the prevention and control of the HIV/AIDS epidemic in Africa have been heavily based on early experiences and policies from industrialised countries, where the disease affects specific risk groups. HIV/AIDS has been dealt with differently from other sexually transmitted or lethal infectious diseases, despite being Africas leading cause of death. In this review, we discuss the evolution of the global response to the epidemic, and the importance of redefining HIV/AIDS in Africa as a public health and infectious disease emergency. We discuss reconsideration of policies and practice around HIV testing and partner notification, and emphasise the need for an increased focus on treatment. Human-rights based approaches to HIV/AIDS prevention might have reduced the role of public health and social justice, which offer a more applied and practical framework for HIV/AIDS prevention and care in Africas devastating epidemic.

The HIV-associated tuberculosis epidemic-when will we act?

A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.).

Morbidity and Mortality in South African Gold Miners: Impact of Untreated Disease Due to Human Immunodeficiency Virus

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration.

A cohort of 1792 human immunodeficiency virus (HIV)-positive and 2970 HIV-negative South African miners was observed for 12 months starting in February 1998. All-cause hospitalizations and deaths were significantly associated with HIV infection (respective unadjusted incidence rate ratios, 2.9 and 9.2; respective 95% confidence intervals, 2.5-3.4 and 5.5-16.0). Tuberculosis (TB), bacterial pneumonia, cryptococcosis, and trauma were the major causes of admission for HIV-positive patients, whereas Pneumocystis carinii pneumonia was an uncommon cause (respective admission rates, 8.5, 6.9, 2.2, 6.0, and 0.53 admissions per 100 person-years). Enteritis, bronchitis, urinary tract infections, and soft-tissue infections were also significantly associated with HIV infection. Cryptococcosis caused 44% of deaths among HIV-positive patients. Trauma was the main hazard for HIV-negative men, causing 42% of admissions and 60% of deaths. A broad range of infectious conditions is significantly associated with HIV infection in South African miners. Identification and implementation of effective prophylactic regimens are urgently needed.

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

AIMS To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Triple-Antiretroviral Prophylaxis to Prevent Mother-To- Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

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.