Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon .

OBJECTIVES: The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. METHODS: In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. RESULTS: At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. CONCLUSIONS: Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success.

High HIV prevalence among children presenting for general consultation in rural Cameroon.

Data on the HIV-prevalence children presenting to health care facilities in sub-Saharan Africa are scant in general, and the debate about opportunities for paediatric HIV screening is ongoing. Nine hundred and eighty-one children with unknown HIV-status presenting to a large general paediatric outpatient department in rural Cameroon were tested using the Determine HIV-1/2 rapid test (Abbott), and positive results were confirmed with the Hexagon HIV rapid test (Human Diagnostics). In children younger than 18 months, HIV infection was confirmed by PCR testing. Median age was 1.3 years and 52.8% were of male gender. In 514 children below 18 months of age, 16 (3.1%) tested positive. Of those, HIV-1 PCR was available for 11 children, of whom 6 had a positive PCR result. HIV prevalence was highest in the age group 5-9 years, being 8.8%. Malnutrition (33.3 vs 5.2%, p < 0.001) was associated with HIV infection. Our study results indicate that HIV testing should be offered to all children at possible entry points to medical care, irrespective of symptoms, in order to reduce HIV-associated mortality through timely initiation of antiretroviral therapy.

Anterior and upward displacement of the inferior mesenteric vein:a new diagnostic clue to left paraduodenal hernias?

A 26-year-old man with acute deterioration of recurrent abdominal pain was admitted to the hospital. Plain film (abdominal radiographs), spiral computed tomography (CT), and barium contrast studies were performed. A left paraduodenal hernia causing acute jejunal obstruction was identified on upper gastrointestinal barium studies and spiral CT. Pre- and postsurgery examinations were compared, and relevant radiological findings were identified. Spiral CT provided excellent visualization of the pathognomonic displacement of the inferior mesenteric vein.

Synergistic effects of trans-4-acetylaminostilbene and 2-acetylaminofluorene at the level of tumor initiation.

The synergism of two carcinogenic aromatic amines with different tissue specificities was studied at the level of initiation in Wistar rats. Gamma-glutamyl transpeptidase and glutathione S-transferase P were used as markers for preneoplastic foci in liver. 2-Acetylaminofluorene (AAF) is a complete rat liver carcinogen, whereas trans-4-acetylaminostilbene (AAS) produces ear duct tumors quite selectively, but also acts as a strong initiator in rat liver. When these carcinogens were administered sequentially as two doses of each or simultaneously as four doses of a mixture to neonate animals, which then were treated with phenobarbital in the drinking water for promotion, the initiating activity was additive. When these chemicals were given to young adult animals within 4 weeks in two series of four doses, followed by partial hepatectomy and phenobarbital in the drinking water, the number of preneoplastic foci was greater in groups which had received AAS in both series or in the second series after AAF than in those groups which had received only AAF or AAF in the second series. The average size of foci depended clearly on the sequence in which the two carcinogens were administered. The foci were larger when AAF was given after AAS. The results support the notion that AAS is a strong initiator in rat liver, and that AAF, which is a complete liver carcinogen, has promoting properties under certain circumstances in addition to its initiating properties. The two carcinogens seem to produce the initiating lesions independently but the extent of initiation is additive in this model situation. The simplified neonatal rat liver model appears to be particularly suitable for investigating initiating properties and is proposed for studies of synergistic effects of genotoxic chemicals on the initiation stage, independent of organotropism. It avoids a number of complicating factors related to treatment schedule, forced proliferation rate and toxicity in other models.

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

It has been demonstrated in several model systems that tumors arise in a multistage process. Carcinogenic aromatic amines are complete carcinogens, which usually produce tumors in typical target tissues without any additional treatment. The tissue specificity, however, cannot readily be explained by genotoxic effects, and the role of secondary effects is not well understood. Promotional pressure on initiated cells can be produced by endogenous factors but also by the chemical itself. Comparison of the effects on rat liver of 2-acetylaminofluorene (AAF) and trans-4-acetylaminostilbene (AAS) provides some evidence that initiating and promoting properties of these chemicals can be separated. AAS is a strong initiator in rat liver but seems to lack promoting activity; AAF is a less efficient initiator but has tumor promoting properties. The results obtained so far indicate that promoting pressure is not produced by the acute, cytotoxic effects of AAF. It is therefore concluded that nongenotoxic, possibly receptor-mediated effects are involved.