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Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.Methods and Findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria.Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses. [ABSTRACT FROM AUTHOR]

We investigated the impact of the displacement of sexual activity from adherent recipients of an intervention to others within or outside a trial population on the results from hypothetical trials of different sexual behavior interventions. A short-term model of HIV-prevention interventions that lead to female rejection of male partnership requests showed the impact of displacement expected at the start of a trial. An agent-based model, with sexual mixing and other South African specific demographics, evaluated consequences of displacement for sexual behavior interventions targeting young females in South Africa. This model measured the cumulative incidence among adherent, non-adherent, control and non-enrolled females in a hypothetical trial of HIV prevention. When males made more than one attempt to seek a partnership, interventions reduced short-term HIV infection risk among adherent females, but increased it among non-adherent females as well as controls, non-enrolled (females eligible for the trial but not chosen to participate) and ineligible females (females that did not qualify for the trial due to age). The impact of displacement depends on the intervention and the adherence. In both models, the risk to individuals who are not members of the adherent intervention group will increase with displacement leading to a biased calculation for the effect estimates for the trial. Likewise, intent-to-treat effect estimates become nonlinear functions of the proportion adherent. [ABSTRACT FROM AUTHOR]

Objective: To compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU). Methods: In a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models. Results: Eleven sites enrolled 209 PHIV and 126 PHEU. Higher DT scores were observed in participants who were PHIV [Adjusted Mean Ratio (aMR) = 1.7 (95% CI 1.2–2.5)], female [aMR = 1.4 (1.0–1.9)], had no source of regular dental care [aMR = 2.3 (1.5–3.4)], and had a high frequency of meals/snacks [≥5 /day vs 0–3, aMR = 1.9 (1.1–3.1)] and juice/soda [≥5 /day vs 0–3, aMR = 1.6 (1.1–2.4)]. Higher DMFT scores were observed in participants who were older [≥19, aMR = 1.9 (1.2–2.9)], had biological parent as caregiver [aMR = 1.2 (1.0–1.3)], had a high frequency of juice/soda [≥5 /day vs 0–3, aMR = 1.4 (1.1–1.7)] and a low saliva flow rate [mL/min, aMR = 0.8 per unit higher (0.6–1.0)]. Eighty percent had PD; no differences were seen by HIV status using the patient-based classifications of health, gingivitis or mild, moderate, or severe periodontitis. No associations were observed of CD4 count and viral load with oral health outcomes after adjustment. Conclusions: Oral health was poor in PHIV and PHEU youth. This was dismaying since most HIV infected children in the U.S. are carefully followed at medical health care clinics. This data underscore the need for regular dental care. As PHIV youth were at higher risk for cavities, it will be important to better understand this relationship in order to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Background: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa. Methods: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003–2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage. Findings: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi’s sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%). Interpretation: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa. [ABSTRACT FROM AUTHOR]

Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV. [ABSTRACT FROM AUTHOR]

Objective The objective was to determine individual and dyadic factors associated with effective contraceptive use among human immunodeficiency virus (HIV)-infected women accessing antiretroviral therapy (ART) in rural Uganda. Study design HIV-infected women enrolled in the Uganda AIDS Rural Treatment Outcomes cohort completed questionnaires (detailing sociobehavioral characteristics, sexual and reproductive history, contraceptive use, fertility desires) and phlebotomy (October 2011–March 2013). We describe prevalence of effective contraceptive use (i.e., consistent condom use and/or oral contraceptives, injectable hormonal contraception, intrauterine device, female sterilization) in the previous 6 months among sexually active, nonpregnant women (18–40 years). We assessed covariates of contraceptive use using multivariable logistic regression. Results A total of 362 women (median values: age 30 years, CD4 count 397 cells/mm 3 , 4.0 years since ART initiation) were included. Among 284 sexually active women, 50% did not desire a(nother) child, and 51% had a seroconcordant partner. Forty-five percent ( n = 127) reported effective contraceptive use, of whom 57% ( n = 72) used condoms, 42% ( n = 53) injectables, 12% ( n = 15) oral contraceptives and 11% ( n = 14) other effective methods. Dual contraception was reported by 6% ( n = 8). Only “partnership fertility desire” was independently associated with contraceptive use; women who reported that neither partner desired a child had significantly increased odds of contraceptive use (adjusted odds ratio: 2.40, 95% confidence interval: 1.07–5.35) compared with women in partnerships where at least one partner desired a child. Conclusions Less than half of sexually active HIV-infected women accessing ART used effective contraception, of which 44% ( n = 56) relied exclusively on male condoms, highlighting a continued need to expand access to a wider range of longer-acting female-controlled contraceptive methods. Association with partnership fertility desire underscores the need to include men in reproductive health programming. Implications statement Less than half of sexually active HIV-infected women accessing ART in rural Uganda reported using effective contraception, of whom 44% relied exclusively on the male condom. These findings highlight the need to expand access to a wider range of longer-acting, female-controlled contraceptive methods for women seeking to limit or space pregnancies. Use of contraception was more likely when both the male and female partner expressed concordant desires to limit future fertility, emphasizing the importance of engaging men in reproductive health programming. [ABSTRACT FROM AUTHOR]