Debra L. Hanson

Incidence of Types of Cancer among HIV-Infected Persons Compared with the General Population in the United States, 1992–2003

BACKGROUND Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population. OBJECTIVE To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003. DESIGN Prospective observational cohort studies. SETTING United States. PATIENTS 54,780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47,832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157,819 person-years of follow-up from 1992 to 2003, and 334,802,121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries. MEASUREMENTS Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population. RESULTS The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time. LIMITATIONS Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated. CONCLUSION The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003.

Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy.

The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

Prevalence of Chronic Hepatitis B and Incidence of Acute Hepatitis B Infection in Human Immunodeficiency Virus–Infected Subjects

We determined incidence and risk factors for acute and chronic hepatitis B virus (HBV) infection and HBV vaccination rates among human immunodeficiency virus (HIV)-infected subjects from the Adult/Adolescent Spectrum of HIV Disease Project, during 1998-2001. Among 16,248 HIV-infected patients receiving care, the incidence of acute HBV was 12.2 cases/1000 person-years (316 cases), was higher among black subjects (rate ratio [RR], 1.4; 95% confidence interval [CI], 1.0-2.0), subjects with alcoholism (RR, 1.7; 95% CI, 1.2-2.3), subjects who had recently injected drugs (RR, 1.6; 95% CI, 1.1-2.4), and subjects with a history of AIDS-defining conditions (RR, 1.5; 95% CI, 1.2-1.9) and was lower in those taking either antiretroviral therapy (ART) with lamivudine (RR, 0.5; 95% CI, 0.4-0.6), ART without lamivudine (RR, 0.5; 95% CI, 0.3-0.7), or >/=1 dose of HBV vaccine (14% of subjects) (RR, 0.6; 95% CI, 0.4-0.9). Prevalence of chronic HBV was 7.6% among unvaccinated subjects. HBV rates in this population were much higher than those in the general population, and vaccination levels were low. HBV remains an important cause of comorbidity in HIV-infected persons, but ART and vaccination are associated with decreased disease.

Pneumococcal Disease among Human Immunodeficiency Virus-Infected Persons: Incidence, Risk Factors, and Impact of Vaccination

To determine the factors associated with pneumococcal disease (pneumococcal pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV-infected persons, we analyzed patient data collected by the Adult and Adolescent Spectrum of HIV Disease Project for person-time between January 1990 and December 1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000 py). Factors associated with an increased risk for pneumococcal disease (P < .05) included injection drug use (adjusted relative risk [RR], 1.5) and blood transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex); black race/ethnicity (RR, 1.5; referent, white race); history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR, 3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR, 2.0). Factors associated with a decreased risk included prescription of antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that pneumococcal vaccine be given to HIV-infected persons before profound immunosuppression has occurred.

Complete Protection from Repeated Vaginal Simian-Human Immunodeficiency Virus Exposures in Macaques by a Topical Gel Containing Tenofovir Alone or with Emtricitabine

ABSTRACT New-generation gels that deliver potent antiretroviral drugs against human immunodeficiency virus type 1 have renewed hopes for topical prophylaxis as a prevention strategy. Previous preclinical research with monkey models suggested that high concentrations and drug combinations are needed for high efficacy. We evaluated two long-acting reverse transcriptase inhibitors, tenofovir (TFV) and emtricitabine (FTC), by using a twice-weekly repeat challenge macaque model and showed that a preexposure vaginal application of gel with 1% TFV alone or in combination with 5% FTC fully protected macaques from a total of 20 exposures to simian-human immunodeficiency virus SF162p3. FTC and TFV were detected in plasma 30 min after vaginal application, suggesting rapid absorption. FTC was detected more frequently than TFV and showed higher levels, reflecting the fivefold-higher concentration of this drug than of TFV. Two of 12 repeatedly exposed but protected macaques showed limited T-cell priming, which did not induce resistance to infection when macaques were rechallenged. Thus, single drugs with durable antiviral activity can provide highly effective topical prophylaxis and overcome the need for noncoital use or for drug combinations which are more complex and costly to formulate and approve.

Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis

OBJECTIVE To examine the effects of antiretroviral therapy (ART) and opportunistic illness chemoprophylaxis on the survival of persons with AIDS and survival time based on year of AIDS diagnosis. DESIGN Longitudinal medical record review. SETTING Ninety-three hospitals and clinics in nine cities in the USA. PATIENTS We observed 19,565 persons with AIDS from 1990 through January 1998. INTERVENTIONS Prescribed use of antiretroviral monotherapy, dual- and triple-combination therapies, primary prophylaxis against Pneumocystis carinii pneumonia and Mycobacterium avium complex, and pneumococcal vaccine. MAIN OUTCOME MEASURES Time from AIDS diagnosis to death in the presence and absence of ART. Survival curves were compared of AIDS cases diagnosed during 1990-1992 and 1993-1995. RESULTS Triple ART had the greatest effect on the risk of death [relative risk (RR), 0.15; 95% confidence limit (CL), 0.12, 0.17], followed by dual ART (RR, 0.24; 95% CL, 0.22, 0.26), and monotherapy (RR, 0.38; 95% CL, 0.36, 0.40). Risk of death was decreased among persons receiving Pneumocystis carinii pneumonia prophylaxis (RR, 0.79; 95% CL, 0.70, 0.89) and Mycobacterium avium complex prophylaxis (RR, 0.76; 95% CL, 0.68, 0.86). Median survival increased from 31 months [95% confidence interval (CI), 30-32 months] for AIDS cases diagnosed during 1990-1992 to 35 months (95% CI, 35-38 months) for cases diagnosed during 1993-1995. CONCLUSIONS The risk of death was decreased for persons receiving triple ART compared with persons receiving dual therapy and persons receiving monotherapy. Increased use of ART and improved ART regimens probably contributed to prolonged survival of persons whose diagnosis was made during 1993-1995 compared with persons whose diagnosis was made during 1990-1992.

Intermittent Prophylaxis with Oral Truvada Protects Macaques from Rectal SHIV Infection

Treating monkeys with single doses of an antiretroviral drug before and after exposure to SHIV provides protection against infection, a schedule that may prove practical in humans. Rearranging Retroviral Regimens for HIV Antiretroviral drugs have transformed the lives of HIV-infected people by preventing progression to full-blown AIDS. These drugs also dramatically reduce HIV transmission from mothers to infants during pregnancy and breastfeeding, and work in monkeys suggests that daily doses can also reduce transmission from unprotected sex. But prophylactic treatment with antiretroviral drugs is costly and impractical—even if confined to a high-risk population. García-Lerma et al. now show that in monkeys a more realistic medication schedule may work just as well as daily doses. To simulate how people are likely to be infected with HIV, the authors exposed macaque monkeys rectally to 14 weekly doses of simian-human immunodeficiency virus (SHIV) engineered to resemble the human virus. Control macaques treated in this way became infected within the first five exposures to SHIV. Researchers then assessed whether oral, human-equivalent doses of antiretroviral agents could prevent infection in monkeys. The best protection—equivalent to that provided by daily antivirals—occurred when the drug Truvada was given 1, 3, or 7 days before virus exposure followed by a second dose 2 hours after exposure. Less effective, but still better than no treatment at all, was a schedule in which the drug was given 2 hours before or after exposure and then again 24 hours later. Drugs given only 24 or 48 hours after exposure did not safeguard against infection. The results of this study are preliminary, largely because each of the groups had only six macaques, but they are nevertheless promising. If ongoing clinical trials in healthy people show that daily antiretroviral therapy can diminish the chances of acquiring HIV after exposure, a reasonable next step would be to evaluate more practical, less costly drug schedules in humans. For example, a weekly dose followed by a second dose after a possible exposure could prove both effective and tractable. It will also be important to evaluate treatments based solely on exposure, as these would not require ongoing prophylactic drug treatment and would minimize any drug toxicity. If one or more of these therapeutic regimens is successful, antiretroviral drugs may expand the transformation they have already engendered by preventing many more new infections as well as controlling existing ones. HIV continues to spread globally, mainly through sexual contact. Despite advances in treatment and care, preventing transmission with vaccines or microbicides has proven difficult. A promising strategy to avoid transmission is prophylactic treatment with antiretroviral drugs before exposure to HIV. Clinical trials evaluating the efficacy of daily treatment with the reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) or Truvada (TDF plus emtricitabine) are under way. We hypothesized that intermittent prophylactic treatment with long-acting antiviral drugs would be as effective as daily dosing in blocking the earliest stages of viral replication and preventing mucosal transmission. We tested this hypothesis by intermittently giving prophylactic Truvada to macaque monkeys and then exposing them rectally to simian-human immunodeficiency virus (SHIV) once a week for 14 weeks. A simple regimen with an oral dose of Truvada given 1, 3, or 7 days before exposure followed by a second dose 2 hours after exposure was as protective as daily drug administration, possibly because of the long intracellular persistence of the drugs. In addition, a two-dose regimen initiated 2 hours before or after virus exposure was effective, and full protection was obtained by doubling the Truvada concentration in both doses. We saw no protection if the first dose was delayed until 24 hours after exposure, underscoring the importance of blocking initial replication in the mucosa. Our results show that intermittent prophylactic treatment with an antiviral drug can be highly effective in preventing SHIV infection, with a wide window of protection. They strengthen the possibility of developing feasible, cost-effective strategies to prevent HIV transmission in humans.

A peer-education intervention to reduce injection risk behaviors for Hiv and hepatitis C virus infection in young injection drug users

Objectives:To evaluate whether a behavioral intervention, which taught peer education skills, could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection (HCV) among young injection drug users (IDU). Design:We conducted a randomized controlled trial involving HIV and HCV antibody-negative IDU, aged 15–30 years, recruited in five United States cities. A six-session, small-group, cognitive behavioral, skills-building intervention in which participants were taught peer education skills (n = 431) was compared with a time-equivalent attention control (n = 423). Baseline visits included interviews for sociodemographic, psychosocial, and behavioral factors during the previous 3 months; HIV and HCV antibody testing; and pre/posttest counselling. Procedures were repeated 3 and 6 months postintervention. Results:The intervention produced a 29% greater decline in overall injection risk 6 months postintervention relative to the control [proportional odds ratio 0.71; 95% confidence limit (CL) 0.52, 0.97], and a 76% decrease compared with baseline. Decreases were also observed for sexual risk behaviors, but they did not differ by trial arm. Overall HCV infection incidence (18.4/100 person-years) did not differ significantly across trial arms (relative risk 1.15; 95% CL 0.72, 1.82). No HIV seroconversions were observed. Conclusion:Interventions providing information, enhancing risk-reduction skills, and motivating behavior change through peer education training can reduce injection risk behaviors, although risk elimination might be necessary to prevent HCV transmission.

Effect of antiretroviral therapy on recent trends in selected cancers among HIV-infected persons

We examined incidence trends in seven HIV-associated cancers (Kaposis sarcoma [KS], invasive cervical cancer, immunoblastic lymphoma, primary brain lymphoma [PBL], Burkitts lymphoma, other non-Hodgkins lymphomas, and Hodgkins lymphoma) and the effects of antiretroviral therapy on these trends. Data were abstracted from medical records in 89 hospitals and clinics in nine U.S. cities from January 1994 through June 1997. The stratified Cochran-Mantel-Haenszel statistic was used to test for trend. There were 19,684 HIV-infected persons representing 26,638 years of follow-up. Decreases in incidence per 1000 person-years were observed for KS (January through June 1994, 49.9; January through June 1997, 25.7; p = .001) and PBL (January through June 1994, 8.0; January through June 1997, 2.3; p = .01), especially during time on antiretroviral therapy, but changes in the incidence of other cancers were not significant. During the study, prescription of combination antiretroviral therapy increased from 16% to 57%. The incidences of KS and PBL are decreasing. Although for KS the decline occurred in both treated and untreated groups (difference in rate of decline not significant, p = .08), it was sharper in the treated group; additionally, KS declined faster in the era after highly active antiretroviral agents were introduced. Thus, these decreases may be due in part to the effect of antiretroviral therapy slowing the progression of HIV disease.

Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral therapy

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 < .001). Conclusion: Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.