Determinants of HIV‐1 drug resistance in treatment‐naïve patients and its clinical implications in an antiretroviral treatment program in Cameroon

Abstract

IntroductionFacing the rapid scale-up of antiretroviral treatment (ART) programs in resource-limited settings, monitoring of treatment outcome is essential in order to timely detect and tackle drawbacks [1].MethodsIn a prospective cohort study, 300 consecutive patients starting first-line ART were enrolled between 2009 and2010 in a large HIV treatment centre in rural Cameroon. Patients were followed up for 12 months. Virologic failure was defined as a VL >1000 cop/mL at month 12. Besides CD4 and viral load (VL) analysis, HIV-1 drug resistance testing was performed in patients with VL>1000 copies (c)/mL plasma. In those patients and controls, minority HIV-1 drug resistance mutations at baseline, and plasma drug levels were analyzed in order to identify the risk factors for virologic failure.ResultsMost enrolled patients (71%) were female. At baseline median CD4 cell count was 162/µL (IQR 59-259), median log10 VL was 5.4 (IQR 5.0–5.8) c/mL, and one-third of patients had World Health Organisation (WHO) stage 3 or 4; 30 patients died during follow-up. Among all patients who completed follow-up 38/238 had virologic failure. These patients were younger, had lower CD4 cell counts and more often had WHO stage 3 or 4 at baseline compared to patients with VL<1000c/mL. Sixty-three percent of failing patients (24/38) had at least one mutation associated with high-level drug resistance. The M184V mutation was the most frequently detected nucleoside reverse transcriptase inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi-NRTI resistance mutations (n=4). The most commonly observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A (n=6). Drug resistance mutations at baseline were detected in 12/65 (18%) patients, in 6 patients with and 6 patients without virological failure (p=0.77). Subtherapeutic NNRTI levels (OR 6.67, 95% CI 1.98–22.43, p<0.002) and poorer adherence (OR 1.54, 95% CI 1.00–2.39, p=0.05) were each associated with higher risk of virologic failure in the matched pair analysis. Unavailability of ART at the treatment centre was the single most common cause (37%) for incomplete adherence in these patients.ConclusionsVirologic failure after one year of first-line ART in rural Cameroon was not associated with transmitted drug resistance, but with reduced drug plasma levels and incomplete adherence. Strategies to assure adherence and uninterrupted drug supply are important factors for therapy success.

Transmitted HIV-1 Drug-resistance Mutations among Newly Diagnosed Patients of the North Western Region of Cameroon

“…The present study detected moderated levels (11.1 %) of TDR which was higher than the 7.3% and 7.55% recorded in the Centre region of Cameroon [7,11] and10.4 % from rural and urban towns in Cameroon [23]. However, it was lower than the 13.9% from the South west region [24], and 18.8% from rural villages in Cameroon [17]. In addition TDR rates ranging from 4.9%-8% has also been recorded in children [15,23] in pregnant women [25] from Cameroon.…”

“…In Cameroon, studies have shown that there is increasing prevalence of TDR over time and ranging from 1 to 10.4% [15][16][17]. Nevertheless, these studies were designed only for a particular locality like Centre, and Littoral regions.…”

<p>Determinants of Virological Failure Among Patients on First-line Antiretroviral Therapy in Central Oromia, Ethiopia: A Case–Control Study</p>

“…18 Diversified factors were associated with ART failure in general and with the virological failure in particular. 19,20 Factors that determine ART outcome may differ from one context to another. Therefore, understanding factors that determine the virological failure among patients on ART is important to inform HIV/AIDS prevention and control program stakeholders.…”

“…These determinants were among those reported in studies in in the country and in other similar African countries. 19,20,[23][24][25][26][27] Under the assumptions, calculation using the variable "five year or more duration on ART" gave largest sample size; that was 504 and consequently, 252 cases and 252 controls were included in this study.…”

Antimicrobial Resistance and Substandard and Falsified Medicines: The Case of HIV/AIDS

“…The proportion for ARVs was 4.2% [2]. People with HIV exposed to subtherapeutic ARVs are at increased risk of developing HIV drug resistance [3,4]. Continued vigilance to ensure use of quality ARVs is critical for three reasons.…”