Virological Suppression and Patterns of Resistance Amongst Patients on Antiretroviral Therapy at 4 Nigerian Military Hospitals.

BACKGROUND: In resource-constrained settings, plasma HIV-1 RNA quantification has not been routinely available for the monitoring of response to antiretroviral therapy. This study evaluated virological suppression rates amongst patients on first-line ART in four Nigerian military hospitals. METHODS: We conducted a cross-sectional study of 325 randomly selected adult clinic clients (≥18 years old) on first-line ART regimens at four Nigerian military hospitals. Plasma HIV-1 RNA was assayed using a Roche COBAS TaqMan48 with High Pure System. Virological failure was defined as HIV-1 RNA >1000 copies/ml. Specimens with HIV-1 RNA >1000 copies/ml were referred for genotyping. RESULTS: HIV-1 RNA results were obtained in 322 participants. Two hundred and seventy-eight study participants (86.3%) had HIV viral RNA < 1000 copies/ml, including 273 (84.8%) with HIV- 1 RNA <400 copies/ml. HIV drug resistance genotyping results were obtained in 35 of 44 study participants with HIV-1 RNA >1000 copies/ml. Only 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (K103N or Y188C). 25% (5/25) of participants failing on Zidovudine had more than two thymidine analogue mutations (TAMs). CONCLUSION: We observed a high virological suppression rate among the study participants. However, a large proportion of virologically unsuppressed clients had identifiable resistance mutations. The study demonstrates that viral load monitoring is feasible at Nigerian military hospitals and supports the current WHO HIV treatment guidelines which emphasize virological monitoring of patients on ART for early detection of treatment failure.

Evaluation of nine HIV rapid test kits to develop a national HIV testing algorithm in Nigeria.

Background: Non-cold chain-dependent HIV rapid testing has been adopted in many resource-constrained nations as a strategy for reaching out to populations. HIV rapid test kits (RTKs) have the advantage of ease of use, low operational cost and short turnaround times. Before 2005, different RTKs had been used in Nigeria without formal evaluation. Between 2005 and 2007, a study was conducted to formally evaluate a number of RTKs and construct HIV testing algorithms. Objectives: The objectives of this study were to assess and select HIV RTKs and develop national testing algorithms. Method: Nine RTKs were evaluated using 528 well-characterised plasma samples. These comprised 198 HIV-positive specimens (37.5%) and 330 HIV-negative specimens (62.5%), collected nationally. Sensitivity and specificity were calculated with 95% confidence intervals for all nine RTKs singly and for serial and parallel combinations of six RTKs; and relative costs were estimated. Results: Six of the nine RTKs met the selection criteria, including minimum sensitivity and specificity (both ≥ 99.0%) requirements. There were no significant differences in sensitivities or specificities of RTKs in the serial and parallel algorithms, but the cost of RTKs in parallel algorithms was twice that in serial algorithms. Consequently, three serial algorithms, comprising four test kits (BundiTM, DetermineTM, Stat-Pak® and Uni-GoldTM) with 100.0% sensitivity and 99.1% - 100.0% specificity, were recommended and adopted as national interim testing algorithms in 2007. Conclusion: This evaluation provides the first evidence for reliable combinations of RTKs for HIV testing in Nigeria. However, these RTKs need further evaluation in the field (Phase II) to re-validate their performance.

Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria.

HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.

Experiences in establishing a PEPFAR-supported laboratory quality system in Nigeria.

The need to accurately diagnose HIV-infected persons and monitor their immune status and sequelae from increased access to antiretroviral therapy dictated the establishment of a quality assurance (QA) system supported by dedicated personnel, financial resources, and a close monitoring system. Assessment of laboratories and personnel in Nigeria revealed the need for improved laboratory infrastructure and training, including on-site didactic and wet workshops and the institution of a tiered QA unit of laboratory regional officers, focal persons, and site monitors who provided guidance and continuous monitoring. Quarterly assessments and generated reports guided corrective actions. A sustainable quality laboratory system was developed for the first time in Nigeria with funding from the US President's Emergency Plan for AIDS Relief. With expansion from 7 to 34 comprehensive treatment sites, a tiered laboratory organizational structure with regional and site-based Nigerian quality control officers was developed. Measured improvements included reduction in deficiencies from 13% to 2%.