1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in North America.

The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome 'snapshot' reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as 'Patient 0' (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.

Reflections on 40 Years of AIDS.

June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions, clarifying optimal use of HIV testing and antiretroviral therapy for prevention and treatment, continuing research, and ensuring sustainability of the response. Despite scientific and programmatic progress, the end of AIDS is not in sight. Other major epidemics over the past decade have included Ebola, arbovirus infections, and coronavirus disease (COVID-19). A benchmark against which to compare other global interventions is the HIV/AIDS response in terms of funding, coordination, and solidarity. Lessons from Ebola and HIV/AIDS are pertinent to the COVID-19 response. The fifth decade of AIDS will have to position HIV/AIDS in the context of enhanced preparedness and capacity to respond to other potential pandemics and transnational health threats.

Preventing Breast, Cervical, and Colorectal Cancer Deaths: Assessing the Impact of Increased Screening.

INTRODUCTION: The US Preventive Services Task Force (USPSTF) recommends select preventive clinical services, including cancer screening. However, screening for cancers remains underutilized in the United States. The Centers for Disease Control and Prevention leads initiatives to increase breast, cervical, and colorectal cancer (CRC) screening. We assessed the number of avoidable deaths from increased screening, according to USPSTF recommendations, for CRC and female breast and cervical cancers. METHODS: We used model-based estimates of avoidable deaths for the lifetime of single-year age cohorts under the current and increased use of screening scenarios (data year 2016; analysis, 2018). We calculated prevented cancer deaths for each 1% increase in screening uptake and extrapolated to current level of screening (2016), current level plus 10 percentage points, and increasing screening to 90% and 100% of the eligible population. RESULTS: Increased use of screening from current levels to 100% would prevent an additional 2,821 deaths from breast cancer, 6,834 deaths from cervical cancer, and 35,530 deaths from CRC over a lifetime of the respective single-year cohort. Increasing use of CRC screening would prevent approximately 8.5 times as many deaths as the equivalent increase in use of breast cancer screening (women only), although twice as many people (men and women) would have to be screened for CRC. CONCLUSIONS: A large number of deaths could be avoided by increasing breast, cervical, and CRC screening. Public health programs incorporating strategies shown to be effective can help increase screening rates.

Potentially preventable deaths from the five leading causes of death--United States, 2008-2010.

In 2010, the top five causes of death in the United States were 1) diseases of the heart, 2) cancer, 3) chronic lower respiratory diseases, 4) cerebrovascular diseases (stroke), and 5) unintentional injuries. The rates of death from each cause vary greatly across the 50 states and the District of Columbia (2). An understanding of state differences in death rates for the leading causes might help state health officials establish disease prevention goals, priorities, and strategies. States with lower death rates can be used as benchmarks for setting achievable goals and calculating the number of deaths that might be prevented in states with higher rates. To determine the number of premature annual deaths for the five leading causes of death that potentially could be prevented ("potentially preventable deaths"), CDC analyzed National Vital Statistics System mortality data from 2008-2010. The number of annual potentially preventable deaths per state before age 80 years was determined by comparing the number of expected deaths (based on average death rates for the three states with the lowest rates for each cause) with the number of observed deaths. The results of this analysis indicate that, when considered separately, 91,757 deaths from diseases of the heart, 84,443 from cancer, 28,831 from chronic lower respiratory diseases, 16,973 from cerebrovascular diseases (stroke), and 36,836 from unintentional injuries potentially could be prevented each year. In addition, states in the Southeast had the highest number of potentially preventable deaths for each of the five leading causes. The findings provide disease-specific targets that states can use to measure their progress in preventing the leading causes of deaths in their populations.

Reflections on 30 years of AIDS.

June 2011 marks the 30th anniversary of the first description of what became known as HIV/AIDS, now one of history's worst pandemics. The basic public health tools of surveillance and epidemiologic investigation helped define the epidemic and led to initial prevention recommendations. Features of the epidemic, including the zoonotic origin of HIV and its spread through global travel, are central to the concept of emerging infectious diseases. As the epidemic expanded into developing countries, new models of global health and new global partnerships developed. Advocacy groups played a major role in mobilizing the response to the epidemic, having human rights as a central theme. Through the commitments of governments and private donors, modern HIV treatment has become available throughout the developing world. Although the end of the epidemic is not yet in sight and many challenges remain, the response has been remarkable and global health has changed for the better.

Men who have sex with men and HIV/AIDS in sub-Saharan Africa.

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda.

Burkitt lymphoma, a childhood tumor common in parts of sub-Saharan Africa, has been directly associated with Epstein-Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case-control study of HIV-seronegative children (

Human herpesvirus 8 presence and viral load are associated with the progression of AIDS-associated Kaposi's sarcoma.

OBJECTIVE: We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8). METHODS: Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies. RESULTS: The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid. CONCLUSIONS: We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.

Cervical cancer screening of women living with HIV infection: a must in the era of antiretroviral therapy.

Women living with human immunodeficiency virus (HIV) infection have a much higher risk of human papillomavirus infection and cervical cancer than do HIV-uninfected women. Before the introduction of antiretroviral therapy, the lack of cervical cancer screening among HIV-infected women probably had little influence on their life expectancies because of the high competing mortality associated with other causes, but the situation is changing rapidly everywhere. In sub-Saharan Africa, for instance, approximately 400,000 HIV-infected women were receiving antiretroviral therapy in 2005. Funds given to antiretroviral therapy programs in low-resource countries not only support the purchase of drugs, but they also support the development of clinical infrastructures and laboratories. Because women who receive antiretroviral therapy are observed regularly, they can also receive the continuity of care needed for cervical screening. Therefore, the real opportunity to prevent cervical cancer in HIV-infected women in low-resource countries should not be missed, especially as new, inexpensive screening methods (e.g., rapid human papillomavirus tests) are under evaluation.

A case-control study of cancer of the uterine cervix in Uganda.

As part of an epidemiological study of cancer in Uganda, we investigated social, sexual and reproductive factors in relation to the risk of cancer of the uterine cervix. Patients with all cancer types or with benign tumours were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against the human immunodeficiency virus-1 (HIV). The case-control study reported here involves 702 HIV-seronegative women, 343 of whom were diagnosed with cancer of the uterine cervix. Key findings were that the risk of cervical cancer increased linearly with the number of pregnancies [chi2(1)=44.7; P<0.0001]; a woman reporting having had 10 or more children had a roughly seven-fold increase in risk of the tumour as compared with women reporting fewer than four pregnancies (odds ratio=7.1; 95% confidence interval 3.8-13.2). The risk also varied inversely with age at first reported sexual intercourse [chi2(1)=8.4; P=0.004], perhaps reflecting an earlier age of infection with human papillomavirus, the main causal agent. These results are in line with those reported from studies in other countries.

BK virus and cancer in Uganda.

As part of an epidemiological study of cancer in Uganda, we investigated the titre of antibodies against BK virus among 821 people with different cancer types and benign tumours. Among study participants, 790 were considered seropositive for anti-BK virus antibodies and all analyses were conducted on transformed data. The mean optical density (a measure of antibody titre) for all patients combined (including the 31 who were considered seronegative) was 1.03 (standard error 0.01), but was 5% higher in women than in men (P=0.05), and 8% higher among HIV seropositive than seronegative people (P=0.002). Otherwise, there were few consistent associations between anti-BK virus antibodies and any social and lifestyle factor investigated. Differences in the mean optical density for each cancer type were estimated using multivariate analysis of variance with adjustment for sex, age group and HIV serostatus, using all other patients as controls. The mean optical density was about 17% lower among those with oral cancer (optical density 0.86, standard error 0.06; P=0.01, based on 30 patients) and about 20% higher among those with prostate cancer (optical density 1.22, standard error 0.09; P=0.01, based on 11 cases) than among all other patients combined. The number of cases of each cancer was too small to exclude the possibility of these findings arising by chance. No other cancer site or type was significantly associated with low, or with high anti-BK virus antibody titres.

Heterosexual behaviours among men who sell sex to men in coastal Kenya.

OBJECTIVE: African men who have sex with men often sell sex to men, and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). DESIGN: Descriptive behavioural study METHODS: : A novel, validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. RESULTS: Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners, but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence, were more likely to only report insertive anal sex roles, and reported lower frequencies of condomless receptive anal sex than exclusive MSW. CONCLUSION: Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks, but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.

Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV.

OBJECTIVE: To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men. DESIGN: Longitudinal study of 87 HHV-8- and HIV-seropositive men [42 with Kaposi's sarcoma (KS)] during four visits over a 2 month period. METHODS: : Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA. RESULTS: HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22]. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51). CONCLUSIONS: Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.