SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

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Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents

Background Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. Methods We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. Results The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199908193410802

The Prevalence of Hepatitis C Virus Infection in the United States, 1988 through 1994

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression, underscore the difficulties in global prevention and control of HCV. Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.

https://courses.washington.edu/conj504/readings/alter_reading3.pdf

Global epidemiology of hepatitis C virus infection

In examining how researchers assess the quality of individual studies in systematic reviews about prognosis, the authors found that appraisal of the quality of the article, a necessary step in syst...

Evaluation of the quality of prognosis studies in systematic reviews.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)17140-7.pdf

Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis

Background. Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. Methods. Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. Results. Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P = .003) and elective Caesarean section (AOR, 0.33; P = .04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. Conclusions. Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important.

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Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy

Children born to women with HIV-1 infection: natural history and risk of transmission. European Collaborative Study

Objective To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. Design Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). Setting United Kingdom and Ireland. Participants 944 children with perinatally acquired HIV-1 under clinical care. Main outcome measures Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. Results 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > 10 years at last follow up, 193 (20%) are know to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. Conclusion In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.

https://www.bmj.com/content/bmj/327/7422/1019.full.pdf

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

Background Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences. Methods Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status. Results In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10 6 copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies. Conclusions Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection

OBJECTIVE\nTo describe the natural history of vertically acquired human immunodeficiency virus (HIV) infection.\n\n\nDESIGN\nThis was a prospective follow-up study.\n\n\nSETTING\nTen centers of the European Collaborative Study participated.\n\n\nSUBJECTS\nOne hundred twenty-four HIV-infected children were born to women known to be infected at or before the time of delivery since 1986.\n\n\nMAIN OUTCOME MEASURES\nDeaths, acquired immunodeficiency syndrome (AIDS), and HIV-related symptoms and signs were assessed.\n\n\nRESULTS\nIn this cohort, treatment before the onset of AIDS was not universal. Less than 10% of children were treated with Zidovudine or intravenous gamma globulin before 6 months of age, with a steady increase to about 40% after 3 years of life. An estimated 23% (95% confidence interval: 15% to 31%) of infected children develop AIDS before the age of 1 year, and nearly 40% (27% to 50%) by 4 years. Ten percent (5% to 16%) die before age 1 year and 28% (16% to 41%) before age 5 years. Twenty-four months after the AIDS diagnosis, an estimated 48% (36% to 70%) of the children are still alive. Although after the age of 1 year immunologic abnormalities became increasingly common, the proportion of infected children with significant HIV-related symptoms or signs declined.\n\n\nCONCLUSION\nThe progression of disease in this cohort of vertically infected children was not as fast as previously suggested, even though treatment was not widespread. Although infected children have a high risk of developing some manifestation of HIV infection early in life, serious HIV-related symptoms became less frequent with increasing age. This has important implications for health planning and care provision.

CS Peckham

Papers

Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy

Children born to women with HIV-1 infection: natural history and risk of transmission. European Collaborative Study

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection

Natural history of vertically acquired human immunodeficiency virus-1 infection