Jonathan Mermin

Estimated HIV Incidence in the United States, 2006–2009

Background The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology. Methodology We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups. Principal Findings Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%. Conclusions/Significance Overall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence.

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda

Background:The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. Objective:To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. Design and methods:A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants’ HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. Results:Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2–0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. Conclusions:Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.

BACKGROUND Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. METHODS Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. FINDINGS Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

Differences in human immunodeficiency virus care and treatment among subpopulations in the United States.

IMPORTANCE Early diagnosis of human immunodeficiency virus (HIV) infection, prompt linkage to and sustained care, and antiretroviral therapy are associated with reduced individual morbidity, mortality, and transmission of the virus. However, levels of these indicators may differ among population groups with HIV. Disparities in care and treatment may contribute to the higher incidence rates among groups with higher prevalence of HIV. OBJECTIVE To examine differences between groups of persons living with HIV by sex, age, race/ethnicity, and transmission category at essential steps in the continuum of care. DESIGN AND SETTING We obtained data from the National HIV Surveillance System of the Centers for Disease Control and Prevention to determine the number of persons living with HIV who are aware and unaware of their infection using back-calculation models. We calculated the percentage of persons linked to care within 3 months of diagnosis on the basis of CD4 level and viral load test results. We estimated the percentages of persons retained in care, prescribed antiretroviral therapy, and with viral suppression using data from the Medical Monitoring Project, a surveillance system of persons receiving HIV care in select areas representative of all such persons in the United States. PARTICIPANTS All HIV-infected persons in the United States. MAIN OUTCOMES AND MEASURES Percentage of persons living with HIV who are aware of their infection, linked to care, retained in care, receiving antiretroviral therapy, and achieving viral suppression. RESULTS Of the estimated 1,148,200 persons living with HIV in 2009 in the United States, 81.9% had been diagnosed, 65.8% were linked to care, 36.7% were retained in care, 32.7% were prescribed antiretroviral therapy, and 25.3% had a suppressed viral load (≤200 copies/mL). Overall, 857 276 persons with HIV had not achieved viral suppression, including 74.8% of male, 79.0% of black, 73.9% of Hispanic/Latino, and 70.3% of white persons. The percentage of blacks in each step of the continuum was lower than that for whites, but these differences were not statistically significant. Among persons with HIV who were 13 to 24 years of age, only 40.5% had received a diagnosis and 30.6% were linked to care. Persons aged 25 to 34, 35 to 44, and 45 to 54 years were all significantly less likely to achieve viral suppression than were persons aged 55 to 64 years. CONCLUSIONS AND RELEVANCE Significant age disparities exist at each step of the continuum of care. Additional efforts are needed to ensure that all persons with HIV receive a diagnosis and optimal care to reduce morbidity, mortality, disparities in care and treatment, and ultimately HIV transmission. Ensuring that people stay in care and receive treatment will increase the proportion of HIV-infected individuals who achieve and maintain a suppressed viral load.

Human immunodeficiency virus transmission at each step of the care continuum in the United States.

IMPORTANCE Human immunodeficiency virus (HIV) transmission risk is primarily dependent on behavior (sexual and injection drug use) and HIV viral load. National goals emphasize maximizing coverage along the HIV care continuum, but the effect on HIV prevention is unknown. OBJECTIVES To estimate the rate and number of HIV transmissions attributable to persons at each of the following 5 HIV care continuum steps: HIV infected but undiagnosed, HIV diagnosed but not retained in medical care, retained in care but not prescribed antiretroviral therapy, prescribed antiretroviral therapy but not virally suppressed, and virally suppressed. DESIGN, SETTING, AND PARTICIPANTS A multistep, static, deterministic model that combined population denominator data from the National HIV Surveillance System with detailed clinical and behavioral data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project to estimate the rate and number of transmissions along the care continuum. This analysis was conducted January 2013 to June 2014. The findings reflect the HIV-infected population in the United States in 2009. MAIN OUTCOMES AND MEASURES Estimated rate and number of HIV transmissions. RESULTS Of the estimated 1,148,200 persons living with HIV in 2009, there were 207,600 (18.1%) who were undiagnosed, 519,414 (45.2%) were aware of their infection but not retained in care, 47,453 (4.1%) were retained in care but not prescribed ART, 82,809 (7.2%) were prescribed ART but not virally suppressed, and 290,924 (25.3%) were virally suppressed. Persons who are HIV infected but undiagnosed (18.1% of the total HIV-infected population) and persons who are HIV diagnosed but not retained in medical care (45.2% of the population) were responsible for 91.5% (30.2% and 61.3%, respectively) of the estimated 45,000 HIV transmissions in 2009. Compared with persons who are HIV infected but undiagnosed (6.6 transmissions per 100 person-years), persons who were HIV diagnosed and not retained in medical care were 19.0% (5.3 transmissions per 100 person-years) less likely to transmit HIV, and persons who were virally suppressed were 94.0% (0.4 transmissions per 100 person-years) less likely to transmit HIV. Men, those who acquired HIV via male-to-male sexual contact, and persons 35 to 44 years old were responsible for the most HIV transmissions by sex, HIV acquisition risk category, and age group, respectively. CONCLUSIONS AND RELEVANCE Sequential steps along the HIV care continuum were associated with reduced HIV transmission rates. Improvements in HIV diagnosis and retention in care, as well as reductions in sexual and drug use risk behavior, primarily for persons undiagnosed and not receiving antiretroviral therapy, would have a substantial effect on HIV transmission in the United States.

Estimating per-act HIV transmission risk: a systematic review

Background:Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy. Methods:We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors. Results:Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10 000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner. Conclusion:The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda

BACKGROUND Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

Disclosure of HIV Status and Adherence to Daily Drug Regimens Among HIV-infected Children in Uganda

Pediatric adherence to daily drug regimens has not been widely assessed in Africa where majority of HIV infected children live. Using in-depth interviews of 42 HIV-infected children taking ART and/or cotrimoxazole prophylaxis, and 42 primary caregivers, at a comprehensive HIV/AIDS clinic in Uganda, we evaluated their adherence experiences for purposes of program improvement. Daily drug regimens provided by the pediatric clinic included cotrimoxazole prophylaxis as well as ART and cotrimoxazole combined. Complete disclosure of HIV status by caregivers to children and strong parental relationships were related to good adherence. Structural factors including poverty and stigma were barriers to adherence even for children who had had complete disclosure and a supportive relationship with a parent. To ensure adherence to life-extending medications, our findings underscore the need for providers to support caregivers to disclose, provide on-going support and maintain open communication with HIV-infected children taking cotrimoxazole prophylaxis and ART.

Reptiles, Amphibians, and Human Salmonella Infection: A Population-Based, Case-Control Study

To estimate the burden of reptile- and amphibian-associated Salmonella infections, we conducted 2 case-control studies of human salmonellosis occurring during 1996-1997. The studies took place at 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas: all of Minnesota and Oregon and selected counties in California, Connecticut, and Georgia. The first study included 463 patients with serogroup B or D Salmonella infection and 7618 population-based controls. The second study involved 38 patients with non-serogroup B or D Salmonella infection and 1429 controls from California only. Patients and controls were interviewed about contact with reptiles and amphibians. Reptile and amphibian contact was associated both with infection with serogroup B or D Salmonella (multivariable odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2; P<.009) and with infection with non-serogroup B or D Salmonella (OR, 4.2; CI, 1.8-9.7; P<.001). The population attributable fraction for reptile or amphibian contact was 6% for all sporadic Salmonella infections and 11% among persons <21 years old. These data suggest that reptile and amphibian exposure is associated with approximately 74,000 Salmonella infections annually in the United States.

Population-Based Hematologic and Immunologic Reference Values for a Healthy Ugandan Population

ABSTRACT To assess the validity of the reference values for hematologic and immunologic indices currently used in Africa, we evaluated blood samples from 3,311 human immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years. Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all significantly increased with age (P < 0.001) and were independent of gender until the age of 13 years, after which the levels were higher in males than in females (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte counts significantly declined with age until the age of 13 years (P < 0.001), with no differences by gender, while platelet counts declined with age (P < 0.001) and showed differences by gender only among adults older than age 24 years. CD4+- and CD8+-cell counts declined with age until the age of 18 years; thereafter, females had higher counts than males. The absolute values for many of these parameters differed from those reported for populations outside Africa, suggesting that it may be necessary to develop tables of reference values for hematologic and immunologic indices specific for the African population. This may be particularly important with regard to CD4+-cell counts among children because significant differences in absolute and percent CD4+-cell counts exist between the values for Western populations and the values for the population evaluated in our study. These differences could influence the decision to initiate antiretroviral therapy among children infected with HIV.