Addressing the challenges of the HIV care continuum remains a major public health priority in the United States. This is exemplified by the July 2013 Executive Order from the White House which established the HIV Care Continuum Initiative to “mobilize and coordinate Federal efforts in response to recent advances regarding how to prevent and treat HIV infection.”1 This third and final supplemental issue developed by the CFAR HIV Continuum of Care (CoC)/Enhanced Comprehensive HIV Prevention Planning Project (ECHPP) Working Group2 for the Journal of Acquired Immune Deficiency Syndrome (JAIDS) highlights the work of academic investigators from seven cities, four of which include co-authors from local public health departments, to conduct research on the HIV continuum of care. This supplemental issue describes the third series of studies to emerge from an initiative supported by the National Institutes of Health (NIH) Centers for AIDS Research (CFAR) Program designed to stimulate research among the CFARs around the HIV prevention and care continuum. | The present introductory article begins with a brief overview of the CFAR CoC/ECHPP Working Group; continues with synopses of NIH funding opportunities and current CDC programs that have been developed to address the continuum of care; and concludes with a synthesis of the seven articles that are included in this supplement.

The contributions reported in this supplemental issue highlight the relevance of NIH-funded CEWG research to health department-supported HIV prevention and care activities in the 9 US cities with the highest numbers of AIDS cases. The project findings have the potential to enhance ongoing HIV treatment and care services and to advance the wider scientific agenda. The HIV testing to care continuum, while providing a framework to help track progress on national goals, also can reflect the heterogeneities of local epidemics. The collaborative research that is highlighted in this issue not only reflects a locally driven research agenda but also demonstrates research methods, data collection tools, and collaborative processes that could be encouraged across jurisdictions. Projects such as these, capitalizing on the integrated efforts of NIH, CDC, DOH, and academic institutions, have the potential to contribute to improvements in the HIV care continuum in these communities, bringing us closer to realizing the HIV prevention and treatment goals of the NHAS.

In summary, addressing the challenges of the HIV care continuum is critical so that the goals of the NHAS can be achieved. CDC is working closely with federal partners, public health departments, and communities throughout the United States on multiple surveillance, programmatic, and research initiatives to inform and improve outcomes along the HIV care continuum. Currently, a large number of research projects are being conducted to describe the care continuum in various populations, assess and model the impact of interventions, and monitor the quality of care. To contribute to this knowledge base, NIH is working with its academic partners to support research that will inform the optimization of HIV treatment and prevention programs. As part of this focus, the CFAR/APC HIV Continuum of Care Working Group was formed to encourage communication between academic investigators and their local DOHs and to support joint research initiatives that are both timely and relevant to their own cities and environments. Finally, the results presented in this supplement may have implications for jurisdictions beyond those in which the studies were conducted.

OBJECTIVE: To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion. METHODS: From 1998-2002, 4684 high-risk MSM, age 18-60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional hazard model with time-varying covariates. RESULTS: Overall, HIV incidence was 2.7/100 py and was relatively uniform across study sites and study years. HIV incidence was highest among young men and men reporting unprotected sex, recreational drug use, and a history of a sexually transmitted infection. Independent predictors of HIV seroconversion included: age 18-30 years (aHR = 2.4; 95% CI 1.4,4.0), having >10 partners (aHR = 2.4; 95% CI 1.7,3.3), having a known HIV-positive male sex partner (aHR = 1.6; 95% CI 1.2, 2.0), unprotected anal intercourse with HIV positive/unknown male partners (aHR = 1.7; 95% CI 1.3, 2.3), and amphetamine (aHR = 1.6; 95% CI 1.1, 2.1) and popper (aHR = 1.7; 95% CI 1.3, 2.2) use. CONCLUSIONS: HIV seroincidence was high among MSM despite repeated HIV counseling and reported declines in sexual risk behaviors. Continuing development of new HIV prevention strategies and intensification of existing efforts will be necessary to reduce the rate of new HIV infections, especially among young men.

BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00146380 Please see later in the article for the Editors' Summary.

BACKGROUND: The association between HIV infection and invasive cervical cancer that has been reported may reflect differential prevalence of human papillomavirus (HPV) infection or uncontrolled confounding. We conducted a case-control study in a West African population to assess the relationship between HIV infection and invasive cervical cancer, taking into account HPV infection and other potential risk factors for cervical cancer. METHODS: Women with invasive cervical cancer (cases) or normal cervical cytology (controls) were recruited in a hospital-based case-control study in Abidjan, Cote d'Ivoire. Odds ratios and 95% confidence intervals (CI) were estimated in logistic regression analyses controlling for important cofactors. RESULTS: HIV infection was noted in 22/132 (16.7%) cases and 10/120 (8.3%) controls (p = 0.048). High-risk HPV infection was detected in cervical tumor samples from 89.4% of case-participants and in cervical cytology samples in 31.1% of control-participants. In logistic regression analysis, HIV infection was associated with cervical cancer in women with HPV (OR 3.4; 95% CI 1.1-10.8). Among women aged <or= 40 years, risk factors for cervical cancer were high-risk HPV infection (OR 49.3; 95% CI 8.2-295.7); parity > 2 (OR 7.0; 95% CI 1.9-25.7) and HIV infection (OR 4.5; 95% CI 1.5-13.6). Among women aged > 40 years, high-risk HPV infection (OR 23.5; 95% CI 9.1-60.6) and parity > 2 (OR 5.5; 95% CI 2.3-13.4), but association with HIV infection was not statistically significant. CONCLUSIONS: These data support the hypothesis that HIV infection is a cofactor for cervical cancer in women with HPV infection, and, as in all populations, the need for promoting cervical screening in populations with high prevalence of HIV infection.