Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges.
ABSTRACT: Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called 'test and treat' expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care.
Project description:BACKGROUND:Many HIV-infected children are diagnosed with tuberculosis (TB), but the effect of TB treatment on virologic and immunologic response to combination antiretroviral therapy (cART) is not well documented. METHODS:Secondary analysis of a prospective cohort of cART-naive HIV-infected South African children aged 0-8 years initiating cART to assess the effect of TB treatment at the time of cART initiation on virologic suppression (HIV RNA < 50 copies/mL), virologic rebound (HIV RNA > 1000 copies/mL after suppression), and CD4 cell percent (CD4%) increase during the first 24 months of cART. RESULTS:Of 199 children (median age 2.1 years), 92 (46%) were receiving TB treatment at cART initiation. Children receiving and not receiving TB treatment at cART initiation had similar median baseline HIV RNA (5.4 vs. 5.6 copies/mL), median time to virologic suppression (6.2 months in each group, adjusted hazard ratio, 1.36, 95% confidence interval: 0.94 to 1.96), and rates of virologic rebound by 24 months (23% vs. 24%, adjusted hazard ratio 1.53, 95% confidence interval: 0.71 to 3.30). Children on TB treatment had significantly lower median CD4% at baseline (15.3% vs. 18.8%, P < 0.01) and during the first 12 months of cART but experienced similar median increases in CD4% at 6 months (9.9% vs. 9.6%), 12 months (14.2% vs. 11.9%), and 24 months of cART (14.5% vs. 14.2%). Exploratory analyses suggest that children receiving lopinavir/ritonavir-based cART and TB treatment may have inferior virologic and immunologic response compared with children receiving efavirenz-based cART. CONCLUSIONS:Receiving TB treatment at the time of cART initiation did not substantially affect virologic or immunologic response to cART in young children.
Project description:To determine magnitude and reasons of loss to program and poor antiretroviral prophylaxis coverage in prevention of mother-to-child transmission (PMTCT) programs in sub-Saharan Africa.Systematic review and meta-analysis.We searched PubMed and Embase databases for PMTCT studies in sub-Saharan Africa published between January 2002 and March 2012. Outcomes were the percentage of pregnant women tested for HIV, initiating antiretroviral prophylaxis, having a CD4 cell count measured, and initiating antiretroviral combination therapy (cART) if eligible. In children outcomes were early infant diagnosis for HIV, and cART initiation. We combined data using random-effects meta-analysis and identified predictors of uptake of interventions.Forty-four studies from 15 countries including 75,172 HIV-infected pregnant women were analyzed. HIV-testing uptake at antenatal care services was 94% [95% confidence intervals (CIs) 92-95%] for opt-out and 58% (95% CI 40-75%) for opt-in testing. Coverage with any antiretroviral prophylaxis was 70% (95% CI 64-76%) and 62% (95% CI 50-73%) of pregnant women eligible for cART received treatment. Sixty-four percent (95% CI 48-81%) of HIV exposed infants had early diagnosis performed and 55% (95% CI 36-74%) were tested between 12 and 18 months. Uptake of PMTCT interventions was improved if cART was provided at the antenatal clinic and if the male partner was involved.In sub-Saharan Africa, uptake of PMTCT interventions and early infant diagnosis is unsatisfactory. An integrated family-centered approach seems to improve retention.
Project description:Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication in HIV-TB co-infected patients receiving combined antiretroviral therapy (cART). While monocytes/macrophages play major roles in both HIV- and TB-infection individually, a putative contribution of monocytes to the development of TB-IRIS remains unexamined. We performed a genome-wide array analysis on MOs purified from peripheral blood mononuclear cells (PBMCs) obtained before initiation of combined antiretroviral therapy (cART) to verify whether the transcriptome of MOs was already significantly modulated (even before receiving cART) in HIV+/TB+ patients who later developed TB-IRIS compared to control HIV+/TB+ patients who did not develop the complication . The subjects under study included a subset of 18 TB-IRIS patients and controls matched for age, gender and CD4 count.
Project description:The primary aim of this study was to measure HIV-1 persistence following combination antiretroviral therapy (cART) in infants and children. Peripheral blood mononuclear cell (PBMC) HIV-1 DNA was quantified prior to and after 1 year of cART in 30 children, stratified by time of initiation (early, age <3 months, ET; late, age >3 months-2 years, LT). Pre-therapy PBMC HIV-1 DNA levels correlated with pre-therapy plasma HIV-1 levels (r = 0.59, p<0.001), remaining statistically significant (p = 0.002) after adjustment for prior perinatal antiretroviral exposure and age at cART initiation. PBMC HIV-1 DNA declined significantly after 1 year of cART (Overall: -0.91±0.08 log10 copies per million PBMC, p<0.001; ET: -1.04±0.11 log10 DNA copies per million PBMC, p<0.001; LT: -0.74 ±0.13 log10 DNA copies per million PBMC, p<0.001) but rates of decline did not differ significantly between ET and LT. HIV-1 replication exposure over the first 12 months of cART, estimated as area-under-the-curve (AUC) of circulating plasma HIV-1 RNA levels, was significantly associated with PBMC HIV-1 DNA at one year (r = 0.51, p = 0.004). In 21 children with sustained virologic suppression after 1 year of cART, PBMC HIV-1 DNA levels continued to decline between years 1 and 4 (slope -0.21 log10 DNA copies per million PBMC per year); decline slopes did not differ significantly between ET and LT. PBMC HIV-1 DNA levels at 1 year and 4 years of cART correlated with age at cART initiation (1 year: p = 0.04; 4 years: p = 0.03) and age at virologic control (1 and 4 years, p = 0.02). Altogether, these data indicate that reducing exposure to HIV-1 replication and younger age at cART initiation are associated with lower HIV-1 DNA levels at and after one year of age, supporting the concept that HIV-1 diagnosis and cART initiation in infants should occur as early as possible.
Project description:BACKGROUND:The increasing numbers of people living with HIV (PLHIV) who are receiving antiretroviral therapy (ART) have near normal life-expectancy, resulting in more people living with HIV over the age of 50 years (PLHIV50+). Estimates of the number of PLHIV50+ are needed for the development of tailored therapeutic and prevention interventions at country, regional and global level. METHODS:The AIDS Impact Module of the Spectrum software was used to compute the numbers of PLHIV, new infections, and AIDS-related deaths for PLHIV50+ for the years 2000-2016. Projections until 2020 were calculated based on an assumed ART scale-up to 81% coverage by 2020, consistent with the UNAIDS 90-90-90 treatment targets. RESULTS:Globally, there were 5.7 million [4.7 million- 6.6 million] PLHIV50+ in 2016. The proportion of PLHIV50+ increased substantially from 8% in 2000 to 16% in 2016 and is expected to increase to 21% by 2020. In 2016, 80% of PLHIV50+ lived in low- and middle-income countries (LMICs), with Eastern and Southern Africa containing the largest number of PLHIV50+. While the proportion of PLHIV50+ was greater in high income countries, LMICs have higher numbers of PLHIV50+ that are expected to continue to increase by 2020. CONCLUSIONS:The number of PLHIV50+ has increased dramatically since 2000 and this is expected to continue by 2020, especially in LMICs. HIV prevention campaigns, testing and treatment programs should also focus on the specific needs of PLHIV50+. Integrated health and social services should be developed to cater for the changing physical, psychological and social needs of PLHIV50+, many of whom will need to use HIV and non-HIV services.
Project description:To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to cART.Systematic review and meta-analysis of studies reporting HIV RNA and CD4 cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible.Twenty-five eligible cohort studies reported data on 49?578 (range 42-15?646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4 cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86-1.29) at 1-4 months, 0.91 (0.83-1.00) at 6 months, 0.99 (0.94-1.05) at 11-12 months, and 0.99 (0.77-1.28) at 18-48 months. The overall RRRE at 1-48 months was 0.97 (95% confidence interval 0.92-1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 cell count gain between those receiving vs. not receiving TB treatment ranged from -10 to 60?cells/?l (median 27) by 6 months (seven estimates) and -10 to 29 (median 6) by 11-12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis.Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.
Project description:We compared the impact and costs of HIV prevention strategies focusing on youth (15-24 year-old persons) versus on adults (15+ year-old persons), in a high-HIV burden context of a large generalized epidemic.Compartmental age-structured mathematical model of HIV transmission in Nyanza, Kenya.The interventions focused on youth were high coverage HIV testing (80% of youth), treatment at diagnosis (TasP, i.e., immediate start of antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive diagnosed youth, male circumcision for HIV-negative young men, pre-exposure prophylaxis (PrEP) for high-risk HIV-negative females (ages 20-24 years), and cash transfer for in-school HIV-negative girls (ages 15-19 years). Permutations of these were compared to adult-focused HIV testing coverage with condoms and TasP.The youth-focused strategy with ART treatment at diagnosis and condom use without adding interventions for HIV-negative youth performed better than the adult-focused strategy with adult testing reaching 50-60% coverage and TasP/condoms. Over the long term, the youth-focused strategy approached the performance of 70% adult testing and TasP/condoms. When high coverage male circumcision also is added to the youth-focused strategy, the combined intervention outperformed the adult-focused strategy with 70% testing, for at least 35 years by averting 94,000 more infections, averting 5.0 million more disability-adjusted life years (DALYs), and saving US$46.0 million over this period. The addition of prevention interventions beyond circumcision to the youth-focused strategy would be more beneficial if HIV care costs are high, or when program delivery costs are relatively high for programs encompassing HIV testing coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to combination prevention programs among youth.For at least the next three decades, focusing in high burden settings on high coverage HIV testing, ART treatment upon diagnosis, condoms and male circumcision among youth may outperform adult-focused ART treatment upon diagnosis programs, unless the adult testing coverage in these programs reaches very high levels (>70% of all adults reached) at similar program costs. Our results indicate the potential importance of age-targeting for HIV prevention in the current era of 'test and start, ending AIDS' goals to ameliorate the HIV epidemic globally.
Project description:Antiretroviral treatment (ART) coverage is rapidly expanding in sub-Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission, the age composition of the HIV epidemic in the region is expected to change in the coming decades. We quantify the change in the age composition of HIV-infected people in all countries in SSA.We used STDSIM, a stochastic microsimulation model, and developed an approach to represent HIV prevalence and treatment coverage in 43 countries in SSA, using publicly available data. We predict future trends in HIV prevalence and total number of HIV-infected people aged 15-49 years and 50 years or older for different ART coverage levels.We show that, if treatment coverage continues to increase at present rates, the total number of HIV-infected people aged 50 years or older will nearly triple over the coming years: from 3.1 million in 2011 to 9.1 million in 2040, dramatically changing the age composition of the HIV epidemic in SSA. In 2011, about one in seven HIV-infected people was aged 50 years or older; in 2040, this ratio will be larger than one in four.The HIV epidemic in SSA is rapidly ageing, implying changing needs and demands in many social sectors, including health, social care, and old-age pension systems. Health policymakers need to anticipate the impact of the changing HIV age composition in their planning for future capacity in these systems.
Project description:<h4>Background</h4>Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation.<h4>Methodology/principal findings</h4>The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens.<h4>Conclusions/significance</h4>Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation.
Project description:Voluntary medical male circumcision (VMMC) among men who have sex with men (MSM) may protect against HIV acquisition. We conducted a series of analyses to assess if expanded VMMC might reduce HIV incidence among MSM effectively and economically. We used a deterministic compartmental model to project new HIV cases (2016-2026) under annual VMMC coverage rates (?) ranging from 0.0001 to 0.15. The 'number needed to avert' (NNA) is defined as the cumulative number of VMMCs conducted up to that year divided by the cumulative number of HIV cases averted in that specific year. Compared with the baseline circumcision coverage rate, we projected that new HIV cases would be reduced with increasing coverage. By 2026 (last year simulated), the model generated the lowest ratio (11.10) when the annual circumcision rate was the most optimistic (??=?0.15). The breakeven point was observed at the year of 2019 with the annual VMMC coverage rate of 0.001. The total cost saved by averting HIV cases would range from 2.5 to 811 million US dollars by the end of 2026 with different hypothetical coverage rates. Our model suggests that acceleration in VMMC implementation among MSM could help stem the HIV/AIDS epidemic.