Rashida A. Ferrand

AIDS among older children and adolescents in Southern Africa: projecting the time course and magnitude of the epidemic.

Objective:An AIDS epidemic among older children and adolescents is clinically apparent in Southern Africa. We estimated the likely scale and time course of the epidemic in older survivors of vertical HIV infection. Design:We modelled demographic, HIV prevalence, mother-to-child transmission and child survival data to project HIV burden among older children in two Southern African countries at different stages of severe HIV epidemics. Using measured survival data for children, we estimate that 64% of HIV-infected infants are fast progressors with median survival 0.64 years and 36% are slow progressors with median survival 16.0 years. We confirmed model validity by comparing model predictions to available epidemiological data. Findings:Without treatment, HIV prevalence among 10-year-olds in South Africa is expected to increase from 2.1% in 2008 to 3.3% in 2020, whereas in Zimbabwe, it will decrease from 3.2% in 2008 to 1.6% in 2020. Deaths among untreated slow progressors will increase in South Africa from 7000/year in 2008 to 23 000/year in 2030, and in Zimbabwe from 8000/year in 2008 to peak at 9700/year in 2014. Drugs to prevent mother-to-child transmission could reduce death rate in 2030 to 8700/year in South Africa and to 2800/year in Zimbabwe in 2014. Conclusions:A substantial epidemic of HIV/AIDS in older survivors of mother-to-child transmission is emerging in Southern Africa. The lack of direct observations of survival in slow progressors has resulted in failure to anticipate the magnitude of the epidemic and to adequately address the clinical needs of HIV-infected older children and adolescents. Better HIV diagnostic and care services for this age group are urgently required.

Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges

Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities.

Causes of Acute Hospitalization in Adolescence: Burden and Spectrum of HIV-Related Morbidity in a Country with an Early-Onset and Severe HIV Epidemic: A Prospective Survey

Rashida Ferrand and colleagues show that HIV infection is the commonest cause of hospitalization among adolescents in a high HIV prevalence setting.

Undiagnosed HIV infection among adolescents seeking primary health care in Zimbabwe.

BACKGROUND Mother-to-child transmission of human immunodeficiency virus (HIV) infection was extremely common in southern Africa during the 1990s, and a substantial minority of infected infants have survived to reach adolescence undiagnosed. Studies have shown a high prevalence of HIV infection in hospitalized adolescents who have features associated with long-standing HIV infection, including stunting and frequent minor illnesses. We therefore investigated the epidemiology of HIV infection at the primary care level. METHODS Adolescents (aged 10-18 years) attending two primary care clinics underwent HIV and Herpes simplex virus-2 (HSV-2) serological testing, clinical examination, and anthropometry. All were offered routine HIV counseling and testing. Patients attending for acute primary care (APC) who were HIV infected were asked about their risk factors. RESULTS Five hundred ninety-four participants were systematically recruited (97% participation), of whom 88 (15%) were attending for antenatal care. HIV infection prevalence was higher among APC attendees than among antenatal care attendees (17% vs 6%; P < .007), but for the prevalence of HSV-2 infection, a marker of sexually acquired HIV, the converse was true (4% vs 14%; P < .002). Seventy (81%) of 86 HIV-positive APC attendees were previously undiagnosed. They had a broad range of presenting complaints, with a median CD4 cell count of 329 cells/microL (interquartile range, 176-485 cells/microL) and a high prevalence of stunting, compared with the corresponding prevalence among HIV-negative attendees (40% vs 12%; P < .001). Maternal transmission was considered to be likely by 69 (80%) of the 86 HIV-positive APC attendees, only one of whom was HSV-2 positive. CONCLUSIONS Unrecognized HIV infection was a common cause of primary care attendance. Routine HIV counseling and testing implemented at the primary care level may provide a simple and effective way of identifying older long-term survivors of mother-to-child transmission before the onset of severe immunosuppression and irreversible complications.

HIV Infection Presenting in Older Children and Adolescents: A Case Series from Harare, Zimbabwe

BACKGROUND Symptomatic human immunodeficiency virus (HIV) infection during late childhood and adolescence may be an emerging problem in southern Africa, but it is one that is poorly described. We investigated social and clinical features in patients of this age group presenting to a HIV treatment clinic with special adolescent services in Harare, Zimbabwe. METHODS All patients aged 8-19 years and their guardians who attended an adolescent HIV treatment clinic were asked to consent to an interview and a review of medical notes. RESULTS Of 32 patients, 17 (53%) were male. The median CD4 cell count at presentation was 101 cells/microL (interquartile range, 35-197 cells/microL). Sixty-two percent experienced stunting (mean Z score for height-for-age, -2.55; 95% CI, -2.00 to -3.10), and all presented with World Health Organization stage 3 or 4 HIV infection. The median age at the first HIV test was 11 years, with a median of 3.5 years delay since the first HIV-related illness. Recurrent respiratory tract infections, skin complaints, diarrhea, and past tuberculosis were the most common HIV-related complaints. Seventeen patients (55%) were double orphans, and 10 (62%) surviving parents were known to be HIV positive. CONCLUSIONS In this small study, HIV-infected adolescents were profoundly immunosuppressed, with characteristics suggesting long-standing HIV infection. The equal sex distribution and high incidence of parental and sibling mortality were consistent; the majority of children had HIV-infected parents and, therefore, were potentially long-term survivors of HIV infection due to mother-to-child transmission. Greater recognition of the substantial burden of undiagnosed HIV infection and acquired immunodeficiency syndrome in this age group is needed, together with services aimed at reducing barriers to earlier diagnosis and initiation of treatment.

Chronic Lung Disease in Adolescents With Delayed Diagnosis of Vertically Acquired HIV Infection

A high burden of chronic lung disease (CLD) was found among 116 consecutive adolescents with vertically acquired human immunodeficiency virus in Zimbabwe. The main cause of HIV-associated CLD appears to be obliterative bronchiolitis, which has not previously been recognized among this patient group.

Survey of children accessing HIV services in a high prevalence setting: time for adolescents to count?

OBJECTIVE To establish the proportion of adolescents among children infected with human immunodeficiency virus (HIV) in Zimbabwe who receive HIV care and support, and what clinic staff perceives to be the main problems faced by HIV-infected children and adolescents. METHODS In July 2008, we sent a questionnaire to all 131 facilities providing HIV care in Zimbabwe. In it we requested an age breakdown of the children (aged 0-19 years) registered for care and asked what were the two major problems faced by younger children (0-5 years) and adolescents (10-19 years). FINDINGS Nationally, 115 (88%) facilities responded. In 98 (75%) that provided complete data, 196 032 patients were registered and 24 958 (13%) of them were children. Of children under HIV care, 33% were aged 0-4 years; 25%, 5-9 years; 25%, 10-14 years; and 17%, 15-19 years. Staff highlighted differences in the problems most commonly faced by younger children and adolescents. For younger children, such problems were malnutrition and lack of appropriate drugs (cited by 46% and 40% of clinics, respectively); for adolescents they concerned psychosocial issues and poor drug adherence (cited by 56% and 36%, respectively). CONCLUSION Interventions for the large cohort of adolescents who are receiving HIV care in Zimbabwe need to target the psychosocial concerns and poor drug adherence reported by staff as being the main concerns in this age group.

Outcomes for Efavirenz versus Nevirapine-Containing Regimens for Treatment of HIV-1 Infection: A Systematic Review and Meta-Analysis

Introduction There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). Methods We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I2 statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds. Results Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73–0.99] I2 = 0%) and observational studies (RR 0.65 [0.59–0.71] I2 = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00–1.08] I2 = 0%) and observational studies (RR 1.06 [1.00–1.12] I2 = 68%). Conclusion EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.

The relationship between HIV and prevalence of disabilities in sub‐Saharan Africa: systematic review (FA)

To systematically review evidence on the prevalence and risk of disabilities among children and adults living with HIV in sub‐Saharan Africa.

Children growing up with HIV infection: the responsibility of success.

1Those working in paediatric HIV care are now cautiously optimistic. Comparing the landscape with 10 years ago when HIVinfected infants faced inevitable death, those born with HIV now have access to antiretroviral therapy (ART) so that increasing numbers of children are surviving to adolescence and beyond. 2 Coupled with this progress, the number of new infections has substantially decreased (from 450 000 in 2005, to 260 000 in 2012) because of scale-up of interventions to prevent mother-to-child HIV transmission (PMTCT), resulting in a shift of burden of HIV towards older children. 3 Additionally, large numbers of children with slowly progressing disease, infected before PMTCT interventions became widely available, are presenting for the fi rst time in adolescence, having lived with untreated HIV for a decade or more. 4