People aging with HIV - protecting a population vulnerable to effects of COVID-19 and its control measures.

Certain comorbidities known to increase the risk of poor outcomes in COVID-19 exist at higher rates in people with HIV; people aging with HIV (PAWH) face additional risk due to the association of advanced age with COVID-19 mortality. Cognitive and functional deficits and social barriers have been identified in cohorts of people aging with HIV. It is postulated that the COVID-19 pandemic potentially threatens PAWH disproportionately to the general population, both in mortality risk due to age and comorbidities, and in potential deleterious effects of policies that seek to drastically limit in-person interaction and access to healthcare systems. A description of and preliminary data from a demonstration project to improve geriatric assessments of people with HIV over age 50 in an urban HIV clinic are presented, in support of this theory. Advice is offered on key strategies utilized to continue to provide care to PAWH during the COVID-19 pandemic, including transition to telemedicine, vaccination, revision of staff roles, repurposing of funding, and a new reliance on available local resources.

Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants.

Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis. Infants born to mothers with TB also received RH preventive therapy. Infant plasma nevirapine concentrations were measured at 1 and 6 weeks. The effects of RH preventive therapy on nevirapine disposition were investigated in a population pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic sampling, 46 received RH preventive therapy. After adjusting for weight using allometric scaling, the model estimated a 33% reduction in nevirapine trough concentrations with RH preventive therapy compared with TB-unexposed infants not receiving concomitant rifampicin and a 30% decline in trough concentrations in a typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB preventative treatment reduces nevirapine concentrations significantly in HIV-exposed infants. Although the nevirapine exposures required to prevent HIV acquisition in breastfeeding infants are undefined, given the potential risks associated with underdosing nevirapine in this setting, it is prudent to avoid rifampicin-based preventive therapy in HIV-exposed children receiving prophylactic nevirapine.

Treatment Failure, Drug Resistance, and CD4 T-Cell Count Decline Among Postpartum Women on Antiretroviral Therapy in South Africa.

BACKGROUND: We assessed HIV RNA suppression, resistance, and CD4 T-cell count 12 months postpartum among pregnant women retained in care in an observational cohort study. METHODS: We prospectively followed two groups of HIV-infected pregnant women--with or without tuberculosis--recruited from prenatal clinics in South Africa. Women who received antiretroviral therapy during pregnancy and reported being on therapy 12 months postpartum were included. Serum samples from women with HIV viremia 12 months postpartum were tested for drug resistance. RESULTS: Of 103 women in the study, median age and CD4 T-cell count at enrollment were 29 years [interquartile range (IQR): 26-32] and 317 cells per cubic millimeter (IQR: 218-385), respectively; 43 (42%) had tuberculosis at baseline. During pregnancy, 87% of the women achieved an HIV RNA <400 copies per milliliter compared with 71% at 12 months postpartum (P < 0.001). Factors independently associated with an HIV RNA <400 copies per milliliter at 12 months were age ≥ 30 years, detectable plasma efavirenz concentration, and HIV RNA <400 copies per milliliter while pregnant; there was a trend toward both a detectable viral load and peripartum depression. HIV drug resistance results were available from 25 women, and 12 (48%) had major drug resistance mutations. CD4 T-cell count declined a median of 13 cells per cubic millimeter (IQR: -66 to 140) from delivery to 12 months in women with viremia at 12 months. CONCLUSIONS: Success with maintaining virologic control declined postpartum among HIV-infected women who remained in care and on antiretroviral therapy, and CD4 T-cell count decline and drug resistance were common.

Tuberculosis and hepatic steatosis are prevalent liver pathology findings among HIV-infected patients in South Africa.

Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.

Maternal hepatitis B and infant infection among pregnant women living with HIV in South Africa.

INTRODUCTION: Globally, hepatitis B virus (HBV) infection is the leading cause of liver-related mortality. Newborn vaccination, maternal antiviral therapy and administering hepatitis B immune globulin shortly after birth can greatly reduce the risk of perinatal and infant infection. However, evidence-based policy regarding these interventions in Africa is hampered by gaps in knowledge of HBV epidemiology. We describe maternal chronic hepatitis B (CHB) prevalence and infant infection during the first year of life within a cohort of women living with HIV. METHODS: We recruited and prospectively followed pregnant women living with HIV and their infants from prenatal clinics in an urban area of South Africa. Hepatitis B surface antigen, anti-hepatitis B surface antibodies and HBV DNA were assessed in all women. Hepatitis B testing was also performed at 6 and 52 weeks for all infants born to mothers with either positive surface antigen or detectable HBV DNA. RESULTS: We enrolled 189 women with a median age of 29 years and median CD4 count of 348 cells/mm(3). Fourteen had a positive surface antigen (7.4%), of which six were positive for "e" antigen. An additional three had detectable HBV DNA without positive surface antigen. One infant developed CHB and three others had evidence of transmission based on positive HBV DNA assays. HBV vaccinations were delivered at six weeks of life to all infants. CONCLUSIONS: Our findings highlight the risk of peripartum HBV transmission in this setting. Approaches to reducing this transmission should be considered.