Efficient monitoring of HIV-1 vertically infected children in Kenya on first-line antiretroviral therapy.

BACKGROUND: Worldwide access to antiretroviral therapy (ART) in low- and middle-income countries has significantly increased. Although this presents better treatment options for HIV-infected individuals, the challenge of monitoring ART in these settings still remains. OBJECTIVE: To investigate efficient and cost-effective criteria for assessing ART failure among HIV-1-infected children on first-line ART in resource-limited settings. STUDY DESIGN: Retrospective analysis of 75 HIV-1 vertically infected Kenyan children with a follow-up period of 24 months after initiating ART. Plasma viral load, peripheral CD4(+)T-cell counts and HIV-1 drug-resistance mutations were monitored biannually. RESULTS: Plasma viral load (VL) was suppressed to undetectable level or more than 1.5 log(10) from baseline levels in 53 (70.7%) children within 24 months. VL in the remaining 22 (29.3%) children was not suppressed significantly. Of the 22 children, 21 were infected with HIV-1 strains that developed drug-resistance mutations; 9 within 12 months and 12 between 12 and 24 months. Among the 53 who were successfully treated, VL was suppressed in 33 within 12 months and in 20 between 12 and 24 months. There was no significant difference in VL at baseline and the change of CD4(+)T-cell counts after initiating ART between those treated successfully and the failure groups. CONCLUSION: After initiating ART, children may require longer times to achieve complete viral suppression. Plasma viral load testing 24 months after initiating ART could be used to differentiate ART failures among HIV-1 vertically infected children in resource-limited settings. Additionally, drug resistance testing, if affordable, would be helpful in identifying those failing therapy and in choosing second-line regimens.

Changes in the HIV type 1 envelope gene from non-subtype B HIV type 1-infected children in Kenya.

A switch of coreceptor usage from CCR5 to CXCR4 occurs in about half of HIV-1-infected individuals in the natural course of infection. To investigate whether antiretroviral therapy (ART) enhances the coreceptor switch of HIV-1, we genotypically analyzed the env-V3 amino acid sequences from 81 HIV-1-infected children in Kenya whose plasma samples were obtained between 2000 and 2007. Of 41 children on ART, 35 had HIV-1 using CCR5 as a coreceptor at baseline. In 7 (20%) of them HIV-1 switched the coreceptor usage during the follow-up period. The mean duration of ART to the time of coreceptor switch was 2.6 years (range: 0.5-5.2). Of the remaining 40 children without ART, 32 had HIV-1 using CCR5 as a coreceptor at baseline and in 3 (9.4%) HIV-1 switched the coreceptor usage. The mean age of the children with HIV-1 coreceptor switch with and without ART was 7.3 and 9.7 years, respectively. The difference in the rate and age of coreceptor switch between treated and untreated children was not significant (p = 0.38 and 0.31, respectively). Of the HIV-1-infected children, 10 started ART by the age of 5 years (rapid progressors) and 23 did not need ART by the age of 10 years (slow progressors). The rate of coreceptor switch was strongly higher in rapid progressors (40%) than slow progressors (8.7%) (p = 0.053). These results suggest that switching of coreceptor usage from CCR5 to CXCR4 among HIV-1-infected children is not influenced by ART, but by factors responsible for rapid disease progression.

Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure.

Recently increased availability of anti-retroviral therapy (ART) has mitigated HIV-1/AIDS prognoses especially in resource poor settings. The emergence of ART resistance-associated mutations from non-suppressive ART has been implicated as a major cause of ART failure. Reverse transcriptase inhibitor (RTI)-resistance mutations among 12 non-subtype B HIV-1-infected children with treatment failure were evaluated by genotypically analyzing HIV-1 strains isolated from plasma obtained between 2001 and 2004. A region of pol-RT gene was amplified and at least five clones per sample were analyzed. Phylogenetic analysis revealed HIV-1 subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1). Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations, K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared with one thymidine-analogue-associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). These results suggest that "vertically transmitted" primary RTI-resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1-infected children could possibly be different from those reported in subtype B-infected children.

Molecular epidemiology of measles virus in Kenya.

Measles causes significant morbidity and mortality globally. Many countries have embarked on immunization programs to control and prevent measles outbreaks and eventually to eliminate endemic measles. Kenya is currently in the outbreak control and prevention stage for measles. Measles virus genotyping is important for molecular epidemiological purposes, including the documentation of the elimination of endemic measles virus strains from a country, and mapping of transmission pathways. In this study, we collected clinical specimens from measles outbreak cases in 2002 in Kenya for measles virus genotyping. We were able to isolate and/or detect measles virus in 10 cases from 5 of the 8 provinces in Kenya. All these Kenyan measles strains were determined to be genotype D4 strains when compared to the standard World Health Organization-designated measles virus reference strains. Interestingly, the Kenyan D4 strains clustered into two distinct D4 subgroups. In addition, the inclusion of other published D4 measles strains in this analysis indicated that there are four distinct D4 clusterings, or subgroups: Montreal-like, India-like, Johannesburg-like, and Ethiopia-like. This is the first measles molecular epidemiology study in Kenya and establishes the current endemic measles strain as genotype D4. Importantly, this study shows that the Kenyan D4 strains are distinct from the B3 measles strain found in West Africa and the D4 strains reported in Ethiopia.

Serological studies and ultrasonographic diagnosis of chronic liver disease in Kenya.

Blood samples were obtained from blood donors and patients with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) from provincial hospitals and Kenyatta National Hospital (KNH). Patients with chronic liver disease (CH, LC and HCC) underwent abdominal ultrasound screening as well. The blood samples were screened for Hepatitis B surface antigen (HBsAg), anti hepatitis C virus (Hep CV) antibodies and alpha fetoprotein (AFP). A total of 44665 blood samples from blood donors were screened for HBsAg between July 1991 and January 1993. Of these 4.1% were found to be HBsAg positive. A total of 983 samples were taken from chronic liver disease patients out of which 22.2% were found to be HBsAg positive. Sixty-three patients were found to have liver cirrhosis and 53 patients had HCC on ultrasound screening. Anti Hep CV antibodies were found in 4.3% (5/116) of patients with LC and HCC. AFP levels were found to be significantly higher in HCC patients than in LC patients, levels of above 200 ng/ml being diagnostic of HCC. Follow up of high risk patients, i.e. those with HBsAg positive, chronic liver disease, by ultrasound screening and AFP detection may be useful in the early detection of HCC.