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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.

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.

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.

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 ¼281) were mapped and surveyed, and questionnaires on condom access and use (n ¼630) 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

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.

M Hamill and colleagues believe the UK could do more to ensure people know their HIV status

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.

TOC summary: Although the end of the epidemic is not yet in sight, the remarkable response has improved health around the world., 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.

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.

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.

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.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the controlgroup comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against H PV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (Cl) 1.2-3.1, P=0.011 and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% Cl 1.7-24.3, P=0.01]. For both cancers, the risk Increased with increasing anti-HPV-16 antibody titre (P t r e n d =0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45.

HIV strains from Zaire indicate the HIV epidemic in Kinshasa was mature by the mid-1980s., Central Africa was the epicenter of the HIV type 1 (HIV-1) pandemic. Understanding the early epidemic in the Democratic Republic of the Congo, formerly Zaire, could provide insight into how HIV evolved and assist vaccine design and intervention efforts. Using enzyme immunosorbent assays, we tested 3,988 serum samples collected in Kinshasa in the mid-1980s and confirmed seroreactivity by Western blot. Polymerase chain reaction of gag p17, env C2V3C3, and/or gp41; DNA sequencing; and genetic analyses were performed. Gene regions representing all the HIV-1 group M clades and unclassifiable sequences were found. From two or three short gene regions, 37% of the strains represented recombinant viruses, multiple infections, or both, which suggests that if whole genome sequences were available, most of these strains would have mosaic genomes. We propose that the HIV epidemic was well established in central Africa by the early 1980s and that some recombinant viruses most likely seeded the early global epidemic.

Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag ) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 ± 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past.

Objective: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV. Design: Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS. Methods: Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed. Results: Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9–39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5–3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4–14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0–10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2–78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0–1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0–1.6) or oral fluids (OR, undefined; P = 0.001). Conclusions: In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.

The association between the prevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) and sociodemographic, sexual, reproductive and lifestyle factors was investigated in a study of adults presenting with cancer at hospitals in Kampala, Uganda. Patients were interviewed and tested for antibodies against KSHV (using an indirect immunofluorescent assay). Data are presented for 607 patients who were not infected with the human immunodeficiency virus-1 (HIV) and who did not have Kaposi's sarcoma (these included people with cancers of the uterine cervix [140], breast [58], liver [41], oesophagus [36], lymphoma [47], other cancers [285] and benign tumours [63]). The prevalence of anti-KSHV antibodies was 50% overall (302/607) and did not differ significantly by cancer site (p = 0.4) or sex (p = 0.2), but increased linearly with age from 35% in those under 25 years to 55% in those 45 years and over (chi(2) trend [1 df] = 9.1; p < 0.001). After adjusting for age and sex, anti-KSHV antibodies were more common in tribal groups other than the Baganda tribe (54% vs. 45% among Baganda; p = 0.02), but there was no significant (p > 0.05) variation in seroprevalence by district of birth, region of residence prior to becoming ill or various measures of wealth. The prevalence of anti-KSHV antibodies decreased with increasing number of older siblings, although this may be due to chance (p = 0.05) and was higher among people who had ever been married (p = 0.03). There was no significant association (p > 0.05) between the presence of antibodies against KSHV and other sexual and reproductive factors. Among the 302 patients with anti-KSHV antibodies, the proportion with high titres increased linearly with increasing age (p = 0.03) and was higher among those reporting having had a blood transfusion (p = 0.03). In conclusion, in this population in Uganda, where KSHV is relatively common, the prevalence of anti-KSHV antibodies increased with age but showed little association with nearly 50 other factors studied.

As part of a larger investigation of cancer in Uganda, we conducted a case-control study of Kaposi's sarcoma in human immunodeficiency virus-1 (HIV)-seronegative adults presenting at hospitals in Kampala. Cases comprised 117 HIV-seronegative patients with Kaposi's sarcoma and controls comprised 1,282 HIV-seronegative patients with a provisional diagnosis of cancer other than Kaposi's sarcoma. Study participants were interviewed about social and lifestyle factors, tested for HIV and, if there was sufficient sera, for antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV8]), using an immunofluorescent assay. Independent effects of these factors were identified using unconditional logistic regression, after adjusting for age group (

Our understanding of tuberculosis (TB) transmission dynamics has been refined by genotyping of Mycobacterium tuberculosis strains. The National Tuberculosis Genotyping and Surveillance Network was designed and implemented to systematically evaluate the role of genotyping technology in improving TB prevention and control activities. Genotyping proved a useful adjunct to investigations of outbreaks, unusual clusters, and laboratory cross-contamination.

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.

Objective: To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998. Methods: Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4 + cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated. Results: There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p = .05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4.1 per 100 py in 1990 to 0.7 per 100 py in 1998; p

These two scenarios raise the question of whether male circumcision should be used in the UK as a means to decrease HIV transmission. Lack of circumcision has long been recognised as a risk factor for HIV acquisition in heterosexual men.1 This makes biological sense because superficial Langerhans cells, which express HIV-1 receptors, are more prevalent in the male foreskin than in the remainder of the penis.2 In addition, decreased keratinisation of the foreskin increases susceptibility to minor trauma during intercourse, potentially aiding the passage of HIV.3 Finally, ulcerative sexually transmitted infections, found more commonly in uncircumcised men, are associated with increased rates of HIV transmission.4 The biological plausibility of adult male circumcision to reduce HIV transmission has now been shown to have clinical relevance in three recent large randomised controlled trials conducted in sub-Saharan Africa, in which male circumcision reduced the rate of female-to-male HIV transmission by at least 50%.5–7 Overall, there was little evidence of increased risk-taking behaviour in circumcised men. Here we examine whether the results of the African trials are relevant in the UK. The yearly number of new HIV diagnoses in the UK has increased by 157% since 1997.8 Of the new diagnoses reported in 2006, 12% were in black African men, most of whom were thought to have been infected heterosexually in Africa, whereas 36% were in men who have sex with men (MSM). Indeed, 2006 saw the greatest yearly number of newly diagnosed HIV infections in MSM since the start of the epidemic. New prevention strategies for these groups are urgently needed. Based on …

Over the past 16 years, the epidemics of HIV infection and AIDS have created many challenges for those working to develop serologic and genetic tests to diagnose infection, antiviral agents to treat infection, and vaccines to prevent infection. Perhaps the greatest challenge comes from the realization that HIV is not a single virus, but a group of related viruses. The remarkable genetic heterogeneity of HIV enables certain HIV strains to elude detection by some of our most widely used serologic assays, to develop resistance to antiviral compounds within weeks to months, and to escape from immune responses generated by natural infection and immunization. This article discusses the range of HIV genetic variation and possible reasons for this variation, and focuses on a specific subset of HIV–1 viruses known as group O .

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.

Kaposi's sarcoma (KS) is associated epidemiologically with HIV infection and with human herpesvirus 8 (HHV-8 or KSHV). Both KS and HIV infection are common in Uganda. We conducted a case-control study of 458 HIV-seropositive. Ugandan adults with KS and 568 HIV-seropositive subjects without KS to examine risk factors for HIV-associated KS.We recruited newly diagnosed adult KS cases from five hospitals in Kampala, Uganda and controls from a large referral clinic for HIV infection at Mulago Hospital. All cases and controls were counselled and tested for HIV and answered an interviewer-administered questionnaire about their home, socio-economic conditions, lifestyle and sexual behaviour before they became ill. Only HIV-seropositive subjects were included in the analysis.There were 295 males and 163 females with KS and 227 male and 341 female controls. Age distribution was similar but there was a higher proportion of cases (45%) than controls (29%) residing in rural regions of Uganda. KS cases were more likely than controls to have a higher level of education (X2 for trend, 4.8; P = 0.03), to have occupations associated with affluence [chi 2 for heterogeneity, 17.3 on 5 degrees of freedom (df); P = 0.004] and to come from larger settlements [adjusted odds ratio (OR) for settlements of1000 versus 10-99 houses, 1.8; 95% confidence interval (CI), 1.1-3.0]. Cases were more likely than controls to have high household income (chi 2 for trend, 32.6; P0.001) and other markers of urban or rural wealth such as owning several cows (chi 2 for trend, 9.5; P = 0.002). Cases were more likely to travel away from home (adjusted OR, 1.6; 95% CI, 1.1-2.3) and more likely to have spent increasing time in contact with water (chi 2 for trend, 12.3; P0.001). Few indices of sexual behaviour were related to risk of KS, including reported number of sexual partners. Cases were more likely than controls to be married to one rather than several spouses (adjusted OR, 1.6; 95% CI, 1.2-2.2) and to have reported a history of sexually transmitted diseases (STD) (adjusted OR, 1.6; 95% CI, 1.2-2.3).Among HIV-infected subjects, KS cases are characterized by better education and greater affluence, compared with controls. Urban address, travel away from home, exposure to water, monogamous marriage and self-reported STD were also more frequent among KS cases than controls. The higher socio-economic status of persons with HIV and KS may be a marker for enhanced exposure to a possibly sexually transmitted agent, or for a delayed exposure to a childhood infection. The risk posed by exposure to water among KS cases requires further study.The risk factors for Kaposi's sarcoma in HIV-infected persons were investigated in a case-control study conducted in Kampala, Uganda, in 1994-96. Cases included 458 HIV-positive Ugandans with newly diagnosed Kaposi's sarcoma, while the control group was comprised of 568 seropositive subjects without Kaposi's sarcoma. Men and women with Kaposi sarcoma were significantly more likely than controls to have a higher educational level, have prestigious professional or military jobs, to come from large settlements (over 1000 houses), to have a high household income, to travel away from home more than seven nights per year, and to have spent increasing time in contact with water. In addition, cases were more likely than controls to be married to one rather than several spouses and to have a history of a sexually transmitted disease. Indices of sexual behavior, including reported number of sexual partners and condom use, were unrelated to Kaposi's sarcoma risk. The higher socioeconomic status of HIV-infected persons with Kaposi's sarcoma may be a marker for enhanced exposure to a sexually transmitted agent such as human herpes virus-8 or for delayed exposure to a childhood infection. The puzzling association between exposure to water and Kaposi's sarcoma warrants further investigation.

Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm.Randomized and blinded case-control study of prospectively collected PBMC samples from ongoing cohort studies.Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination.In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9-13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients.AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

This report reviews data pertaining to the hypothesis that transmission of HIV to five patients of a Florida dentist with AIDS resulted from the patient-to-patient transfer of infectious materials through the reuse of contaminated instruments. Findings strongly suggest that patient-to-patient transmission of HIV through contaminated handpieces, prophylaxis angles or anesthetic needles or cartridges did not occur in this practice.

The causal agent of Kaposi's sarcoma is unknown. That the disorder is ten times more common in homosexual or bisexual men with the acquired immunodeficiency syndrome (AIDS) than in other human immunodeficiency virus (HIV) transmission groups suggests that a certain aspect of their behaviour exposes them to the agent or facilitates its spread. We therefore assessed social and demographic characteristics, including sexual behaviour, of 65 homosexual or bisexual men with AIDS from London. Sexual practices in which there was contact with partner's faeces before AIDS developed were the main determinants of Kaposi's sarcoma risk. Risk increased with frequency of insertive "rimming" (oral-anal contact): Kaposi's sarcoma developed in 18% of the men with AIDS who reported never having practised insertive rimming compared with 50% who practised it less than once a month, 73% between once a week and once a month, and 75% or more once a week (two-sided exact p-value for trend less than 0.001). 45 men had been interviewed about their sexual practices before AIDS developed, and 20 were interviewed at the time the syndrome developed. The findings were similar and statistically significant when each group was analysed separately. The men with Kaposi's sarcoma also tended to be more sexually active and were more likely to engage in other sexual activities that entailed contact with faeces than were the men who had other features of AIDS only. Other behaviours and exposures, including the use of "poppers" (nitrite inhalants), were not related to Kaposi's sarcoma risk, after taking into account whether the subjects had practised insertive rimming. The data suggest that faecal-oral contact is the main route of transmission of the agent of Kaposi's sarcoma in homosexual or bisexual men with AIDS.

A study of risk factors for HIV-1 infection was conducted at a sexually transmitted disease clinic in an area of New York City where the cumulative incidence of AIDS in adults through mid-1990 was 9.1 per 1000 of the population and where the use of illicit drugs, including smokable freebase cocaine (crack), is common. The overall seroprevalence among volunteers was 12% (369 out of 3084), with 80% of those who were seropositive reporting risk behavior associated with HIV-1 infection, including male-to-male sexual contact, intravenous drug use and heterosexual contact with an intravenous drug user. The seroprevalence in individuals denying these risks was 3.6% (50 out of 1389) and 4.2% (22 out of 522) in men and women, respectively. Among these individuals, the behaviors significantly associated with infection were use of crack and prostitution in women, and history of syphilis and crack use in men. These results suggest that in areas where the level of HIV-1 infection in heterosexual intravenous drug users is high and the use of crack is common, increased sexual activity (including the exchange of drugs or money for sex) may result in increased heterosexual transmission of HIV-1.

The work of epidemiologists before the isolation of human immunodeficiency virus 25 years ago demonstrates the power of the epidemiological method to gain an understanding of disease pathogenesis.

The 21st century has witnessed unprecedented increases in funding for global health driven mainly by efforts to address the HIV/AIDS epidemic. The US Presidents Emergency Plan for AIDS Relief (PEPFAR) is the largest single donor having allocated approximately $13 billion for AIDS prevention treatment and care in developing countries and contributed $3 billion to the Global Fund to Fight AIDS Tuberculosis and Malaria since the plans inception in 2003. For the next 5 years the president is seeking a $30 billion appropriation for PEPFAR while Congress is proposing to increase the appropriation to $50 billion and add funding for malaria and tuberculosis programs. In contrast the World Health Organization (WHO) smallpox eradication program conducted from 1967 through 1979 cost less than $2 billion (adjusted for inflation). Funding to provide antiretroviral treatment (ART) for HIVinfected individuals in developing countries is saving lives. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and WHO have reported that global deaths due to AIDS peaked in 2005 and then decreased over the next 2 years a decline at least partially attributed to ART. By the end of 2007 about 3 million individuals living in low- and middle-income countries were receiving ART representing approximately 31% of individuals needing treatment in those areas. While acknowledging the undeniable successes of these treatment programs it is also important to examine some of the problems they may have inadvertently created or magnified: i.e. their unintended consequences as well as their potential for long-term sustainability. This Commentary focuses on PEPFAR and sub-Saharan Africa the region most severely affected by HIV/AIDS. (excerpt)

Background: Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) is not clear.Methodology/Principal Findings: We conducted a case-control study of Burkitt lymphoma among children (aged

To evaluate the correlation of detection of human immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. PCR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and CO71/72. Amplified HIV DNA was detected using specific oligomer probes. Of 63 HIV antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had HIV DNA by PCR. On follow-up, 4 of the latter persons were seropositive when next tested; 2 were well and antibody- and PCR-negative; 1 had died of a stroke before retesting. Thus, PCR detects HIV in most antibody-positive persons; detection is increased by use of multiple primer pairs. PCR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing of additional specimens and clinical follow-up are necessary to assess HIV infection status.

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

For all the advances in treatment of HIV infection, the mainstays of prevention have changed little: sexual abstinence, condoms, sterile injection equipment, avoidance of high-risk behaviours, and knowing one’s own serostatus and that of any sexual or drug-injecting partners. Although these strategies can be eff ective and recent years have seen decreases in new infections in some countries and in some risk groups, the 11 000 new infections daily is ample testament that additional methods of prevention are needed. Evidence for successful HIV-prevention technologies is mixed. Randomised studies of male circumcision in South Africa, Kenya, and Uganda were discontinued early after interim review showed reductions in new HIV infections ranging from 60% to 74% in the circumcised men compared with those who were not circumcised. Several topical microbicides are in advanced trials. However, phase III trials of C-31G (originally developed by Cellegy Pharmaceuticals) and cellulose sulphate (Polydex Pharmaceuticals, Nassau, Bahamas) were terminated early because preliminary results suggested no effi cacy (C-31G) or increased risk of HIV transmission (cellulose sulphate). HIV-vaccine research continues despite two completed trials of AidsVax (VaxGen, South San Francisco, CA, USA) that showed no effi cacy. Proof of effi cacy of any present microbicide or vaccine candidate is several years away, and fi rst products will probably be only moderately eff ective. The need to manufacture such a product in large quantities and distribute it around the world will pose additional challenges.

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.

Understanding whether hormonal contraception increases the risk of incident HIV-1 infection among women is a critical public health issue. Hormonal contraception a novelty just four decades ago has become the norm in many countries because of its high efficacy and ease of use. Over 120 million women worldwide use hormonal contraception and its use especially depo-medroxyprogesterone acetate (DMPA) is increasing rapidly in many resource-limited settings. Effective contraception has a key role to play in reducing maternal and infant mortality (by spacing pregnancies) and in allowing women a measure of control over when and how often they become pregnant. At the same time the HIV/AIDS epidemic has reached crisis proportions in a number of sub-Saharan countries and calls for a rapid expansion of both prevention and treatment in resource-limited settings particularly among women of childbearing age. Despite the magnitude of the HIV/AIDS epidemic the level of condom use among married or cohabiting couples in countries classified by UNAIDS as experiencing a generalized HIV epidemic remains very low. Most women who do use contraception rely on oral contraceptives (OC) or injectable DMPA. (excerpt)

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.

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 (Cl), 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; 9.5% Cl, 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.

A case-control study from Uganda found that the risk of Kaposi's sarcoma increased with increasing titre of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigens, independently of HIV infection. Clinically, widespread Kaposi's sarcoma was more frequent among patients with HIV infection than in those without, but was not related to anti-KSHV antibody titres.

Postexposure prophylaxis (PEP) after intravaginal exposure to human immunodeficiency virus (HIV) was investigated using the HIV type 2 (HIV-2)/pig-tailed macaque transmission model. PEP for 28 days with the reverse transcriptase inhibitor ( R )-9-(2-phosphonylmethoxypropyl)adenine (PMPA; tenofovir) was initiated 12 to 72 h following HIV-2 exposure. Systemic infection was not evident in the 12- and 36-h groups, as defined by plasma viremia, cell-associated provirus, antibody responses, and lymph node virus. Breakthrough infection in the 72-h group was detected at week 16 post-virus exposure. These results demonstrate for the first time using a vaginal transmission model that early intervention after high-risk sexual exposures may prevent infection.

Human herpesvirus 8 (HHV-8) was detected in 1994 in biopsies of Kaposi's sarcoma (KS) tissues from a patient with AIDS. The evidence that HHV-8 infection is etiologically related to the development of KS is compelling. Essentially all patients with KS of any epidemiological type have serological evidence of HHV-8 infection. About 30%-40% of homosexual men infected with human immunodeficiency virus (HIV) are seropositive for HHV-8; rates are lower (

Recent research advances have afforded substantially improved understanding of the biology of HIV infection and the pathogenesis of AIDS. With the advent of sensitive tools for monitoring HIV replication in infected persons, the risk for disease progression and death can be assessed accurately and the efficacy of anti-HIV therapies can be determined directly. Furthermore, when used appropriately, combinations of newly available, potent antiviral therapies can effect prolonged suppression of detectable levels of HIV replication and circumvent the inherent tendency of HIV to generate drug-resistant viral variants. However, as antiretroviral therapy for HIV infection has become increasingly effective, it has also become increasingly complex. Familiarity with recent research advances is needed to ensure that newly available therapies are used in ways that most effectively improve the health and prolong the lives of HIV-infected persons. To enable practitioners and HIV-infected persons to best use rapidly accumulating new information about HIV disease pathogenesis and treatment, the Office of AIDS Research of the National Institutes of Health (NIH) sponsored the NIH Panel To Define Principles of Therapy of HIV Infection. This Panel was asked to define essential scientific principles that should be used to guide the most effective use of antiretroviral therapies and viral load testing in clinical practice. On the basis of detailed consideration of the most current data, the Panel delineated 11 principles that address issues of fundamental importance for the treatment of HIV infection. These principles provide the scientific basis for the specific treatment recommendations made by the Panel on Clinical Practices for the Treatment of HIV Infection sponsored by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. The reports of both of these panels are provided in this supplement. Together, they summarize new data and provide both the scientific basis and specific guidelines for the treatment of HIV-infected persons. This information will be of interest to health care providers, HIV-infected persons, HIV and AIDS educators, public health educators, public health authorities, and all organizations that fund medical care of HIV-infected persons.

To assess the risk for transmission of the human immunodeficiency virus (HIV) from an infected health care worker to patients.Survey of investigators from health departments, hospitals, and other agencies who had elected to notify patients who had received care from health care workers infected with HIV.Information was collected about infected health care workers, their work practices, their patients' HIV test results, procedures that they did on those of their patients who were tested for HIV, and patient notification procedures.As of 1 January 1995, information about investigations of 64 health care workers infected with HIV was reported to the Centers for Disease Control and Prevention; HIV test results were available for approximately 22,171 patients of 51 of the 64 health care workers. For 37 of the 51 workers, no seropositive patients were reported among 13,063 patients tested for HIV. For the remaining 14 health care workers, 113 seropositive patients were reported among 9108 patients. Epidemiologic and laboratory follow-up did not show any health care worker to have been a source of HIV for any of the patients tested.Despite limitations, these data are consistent with previous assessments that state that the risk for transmission of HIV from a health care worker to a patient is very small. These data also support current recommendations that state that retrospective patient notification need not be done routinely.