Evaluating the impact of DREAMS on HIV incidence among adolescent girls and young women: A population-based cohort study in Kenya and South Africa

BackgroundThrough a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women’s heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings.Methods and findingsWe directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years).In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period.ConclusionsSubstantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

Isolde Birdthistle and co-workers evaluate a program to address risks of HIV infection in adolescent girls and young women in sub-Saharan Africa.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Predictors of poor CD4 and weight recovery in HIV-infected children initiating ART in South Africa

Objective

To identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary''s hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008.We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression.

Results

From the initial cohort of 901 children <10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (<400 copies/ml) were 84% after six months of therapy and 88% after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89% after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58% of children after six months of ART and 64% after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4% (p = 0.005), chronic diarrhea (p = 0.02), and virologic failure (p<0.001). Age less than 3 years at ART initiation (p = 0.0003), higher baseline CD4% (p<0.001), and higher baseline WAZ (p<0.001) were all associated with poor WAZ improvements after 6 months by multivariate logistic regression.

Conclusion

The presence of chronic diarrhea at baseline, independent of nutritional status and viral response, predicts poor CD4 recovery. Age at initiation of ART is an important factor in early WAZ response to ART, while viral suppression strongly predicts CD4 recovery but not WAZ improvement.     

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings

HIV-1 drug resistance has the potential to seriously compromise the effectiveness and impact of antiretroviral therapy (ART). As ART programs in sub-Saharan Africa continue to expand, individuals on ART should be closely monitored for the emergence of drug resistance. Surveillance of transmitted drug resistance to track transmission of viral strains already resistant to ART is also critical. Unfortunately, drug resistance testing is still not readily accessible in resource limited settings, because genotyping is expensive and requires sophisticated laboratory and data management infrastructure. An open access genotypic drug resistance monitoring method to manage individuals and assess transmitted drug resistance is described. The method uses free open source software for the interpretation of drug resistance patterns and the generation of individual patient reports. The genotyping protocol has an amplification rate of greater than 95% for plasma samples with a viral load >1,000 HIV-1 RNA copies/ml. The sensitivity decreases significantly for viral loads <1,000 HIV-1 RNA copies/ml. The method described here was validated against a method of HIV-1 drug resistance testing approved by the United States Food and Drug Administration (FDA), the Viroseq genotyping method. Limitations of the method described here include the fact that it is not automated and that it also failed to amplify the circulating recombinant form CRF02_AG from a validation panel of samples, although it amplified subtypes A and B from the same panel.     

Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal,South Africa Using Lot Quality Assurance Sampling

BackgroundKwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses.MethodsBetween July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers.ResultsWe classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border.ConclusionOur study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.