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.

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.

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.

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.

Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi.

Endemic Burkitt lymphoma (eBL) has been linked to Plasmodium falciparum (Pf) malaria infection, but the contribution of infection with multiple Pf genotypes is uncertain. We studied 303 eBL (cases) and 274 non eBL-related cancers (controls) in Malawi using a sensitive and specific molecular-barcode array of 24 independently segregating Pf single nucleotide polymorphisms. Cases had a higher Pf malaria prevalence than controls (64.7% versus 45.3%; odds ratio [OR] 2.1, 95% confidence interval (CI): 1.5 to 3.1). Cases and controls were similar in terms of Pf density (4.9 versus 4.5 log copies, p = 0.28) and having ≥3 non-clonal calls (OR 2.7, 95% CI: 0.7-9.9, P = 0.14). However, cases were more likely to have a higher Pf genetic diversity score (153.9 versus 133.1, p = 0.036), which measures a combination of clonal and non-clonal calls, than controls. Further work is needed to evaluate the possible role of Pf genetic diversity in the pathogenesis of endemic BL.

The evolving epidemiology of HIV/AIDS.

Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact.

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa.

INTRODUCTION: It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. METHODS: We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. RESULTS: Of 1,959 (913 non-Africans, 302 Europeans-African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607 (588-627) (non-African European), 469 (442-497) (European-African origin) and 570 (551-589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228-289), 155 (110-200), and 199 (174-224) cells/µL (p<0.01). DISCUSSION: Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African 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.

Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults.

OBJECTIVE: Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration. DESIGN: A nested matched case-control study design was used to assess the effects of individual CD4 cell trajectories and exposure to cART close to the time of cancer diagnosis. METHODS: Cases were patients diagnosed with either cancer during follow-up with a minimum of two consecutive CD4 cell readings within the year preceding diagnosis. For each case, up to 10 controls, matched by sex and cohort, were selected by random sampling. Changes in CD4 cell count, calculated by simple and piecewise linear regression, and recent exposure to cART were compared within matched case-control sets using conditional logistic regression. RESULTS: Using data on 689 cases and 4588 controls, we found that an initially low and decreasing CD4 cell count during the year prior to cancer diagnosis is predictive of both Kaposi sarcoma and NHL. Most of this cancer risk is explained by the immunodeficiency characteristic of the period before cART initiation; however, an increased cancer risk was seen in patients who initiated cART in the previous 3 months (odds ratio 2.31; 95% confidence interval 1.33, 4.00). CONCLUSION: Although IRIS may transiently increase the risk of Kaposi sarcoma or NHL in HIV-infected patients, the timely initiation of cART remains the best strategy to avoid the development of these malignancies.

Exploring the condom gap: is supply or demand the limiting factor - condom access and use in an urban and a rural setting in Kilifi district, Kenya.

OBJECTIVE: to explore the extent of the condom gap, investigating the relative roles of supply-side and demand-side factors in determining condom use. DESIGN: GPS mapping of condom outlets, and population-based survey. METHODS: an urban and a rural site were selected within the Epidemiological and Demographic Surveillance Site in Kilifi district, Kenya. Potential condom outlets (n = 281) were mapped and surveyed, and questionnaires on condom access and use (n = 630) were administered to a random sample of men and women aged 15-49. Multivariate logistic regression was performed to assess the relative roles of supply-side and demand-side barriers on condom use. RESULTS: the median straight-line distance to free condoms was 18-fold higher in the rural versus urban site. Among sexually active respondents, 42% had ever used a condom, and 23% had used a condom over the past 12 months, with lower levels among rural versus urban respondents (P < 0.05). The mean number of condoms used was 2.2/person per year among all sexually active individuals (condom users and nonusers), amounting to 8.2% protected sex acts/person per year. The adjusted odds of condom use (past 12 months) were 8.1 times greater among individuals experiencing no supply-side or demand-side barriers, compared with individuals experiencing both types of barriers. Despite low levels of usage and the presence of supply-side and demand-side barriers, reported unmet need for condoms was low. CONCLUSIONS: there is an urgent need for renewed condom promotion efforts aimed at building demand, in addition to improving physical access, in resource-limited settings with generalized HIV epidemics in sub-Saharan Africa.

Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings.

BACKGROUND: The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, children (aged /= 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses). RESULTS: Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4). CONCLUSIONS: In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.