Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.

Incidence of and socio-biologic risk factors for spontaneous preterm birth in HIV positive Nigerian women.

BACKGROUND: Recent studies have identified HIV as a leading contributor to preterm delivery and its associated morbidity and mortality. However little or no information exists in our sub-region on this subject. Identifying the factors associated with preterm delivery in HIV positive women in our country and sub-region will not only prevent mother to child transmission of HIV virus but will also reduce the morbidity and mortality associated with prematurity and low birth weight. This study was designed to determine the incidence and risk factors for preterm delivery in HIV positive Nigerians. METHOD: The required data for this retrospective study was extracted from the data base of a cohort study of the outcome of prevention of mother to child transmission at the Nigerian Institute of Medical Research, Lagos. Only data of women that met the eligibility of spontaneous delivery after 20 weeks of gestation were included. Ethical approval was obtained from the Institution's Ethical Review Board. RESULTS: 181 women out of the 1626 eligible for inclusion into the study had spontaneous preterm delivery (11.1%). The mean birth weight was 3.1 ± 0.4 kg, with 10.3% having LBW. Spontaneous preterm delivery was found to be significantly associated with unmarried status (cOR: 1.7;1.52-2.57), baseline CD4 count <200 cells/mm(3) (cOR: 1.8; 1.16-2.99), presence of opportunistic infection at delivery (cOR: 2.2;1.23-3.57), multiple pregnancy (cOR 10.4; 4.24 - 26.17), use of PI based triple ARV therapy (eOR 10.2; 5.52 - 18.8) in the first trimester (cOR 2.5; 1.77 - 3.52) on univariate analysis. However after multivariate analysis controlling for potential confounding variables including low birth weight, only multiple pregnancy (aOR: 8.6; CI: 6.73 - 12.9), presence of opportunistic infection at delivery (aOR: 1.9; CI: 1.1 - 5.7), and 1st trimester exposure to PI based triple therapy (aOR: 5.4; CI: 3.4 - 7.8) retained their significant association with preterm delivery. CONCLUSION: The spontaneous preterm delivery rate among our cohort was 11.1%. HIV positive women with multiple pregnancies, symptomatic HIV infection at delivery and first trimester fetal exposure to PI based triple therapy were found to be at risk of spontaneous preterm delivery. Early booking and non-use of PI based triple therapy in the first trimester will significantly reduce the risk of preterm delivery.

Effect of HIV-1 infection and increasing immunosuppression on menstrual function.

AIM: The aim of this study was to determine the prevalence, pattern and determinants of menstrual abnormalities in HIV-positive Nigerian women. METHODS: A cross-sectional study was carried out involving 3473 (2549 HIV-seropositive and 924 seronegative) consecutive and consenting women seen at the HIV treatment centers at the Nigerian Institute of Medical Research, Lagos and the Federal Medical Centre, Markurdi. RESULTS: The sociodemographic characteristics of the two groups were comparable, except for body mass index (BMI): the HIV-negative women (28.1 ± 8.1) had statistically significantly (P < 0.005) higher BMI compared to the HIV-positive women (21.9 ± 7.5). Menstrual abnormalities were significantly more common in women living with HIV/AIDS (29.1%) compared to the HIV-negative (18.9%) women (P < 0.001). The proportions of women in the two groups with intermenstrual bleeding, menorrhagia, hypermenorrhea, and postcoital bleeding were similar (P > 0.005), however amenorrhea, oligomenorrhea, irregular periods and secondary dysmenorrhea were more common in the HIV-positive women (P < 0.02). Primary dysmenorrhea was less common in HIV-positive women (P < 0.03). Among the HIV-positive women, menstrual dysfunction was more common in women living with HIV/AIDS with opportunistic infections, CD4 count < 200, not undertaking therapy, symptomatic disease and BMI < 20. However, after controlling for cofounders, only CD4 < 200 (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.2-9.7), BMI < 20 (OR, 2.4; 95%CI, 1.3-3.5) and not taking antiretroviral drugs (OR, 2.05; CI, 1.7-6.5) were associated with amenorrhea, oligomenorrhea, irregular periods and secondary dysmenorrhea. CONCLUSION: HIV-positive women in this study experienced more menstrual abnormalities of amenorrhea, oligomenorrhea, and irregular periods compared to the HIV-negative controls. HIV-positive women with CD4 count < 200, BMI < 20 and who do not take antiretroviral drugs are at the greatest risk.

Intimate partner violence and correlates in pregnant HIV positive Nigerians.

OBJECTIVE: To determine the prevalence, types and correlates of intimate partner violence (IPV) in pregnant Nigerian living with HIV. DESIGN: Cross sectional study. POPULATION: HIV positive pregnant women. SETTING: A large HIV comprehensive treatment centre. METHODS: A cross sectional study of 652 HIV positive pregnant Nigerians seen at Nigerian Institute of Medical Research, Lagos, Nigeria over a 24 months period. MAIN OUTCOME MEASURES: Prevalence of intimate partner violence after HIV diagnosis. RESULTS: Among the women interviewed, 423 (65.8%) reported abuse. In 74.0% of abused women, the abuse started after HIV diagnosis. Though having a HIV negative spouse and disclosure of HIV status were associated with abuse, only having a HIV negative partner retained its association with IPV (OR 3.1; CI 2.4-5.3) after controlling for confounding variables. Sixty-two (9.6%) women have not disclosed their HIV status because of fear of rejection. Verbal abuse (51.7%), threat of violence in 97 (22.9%) and sexual deprivation in 91 (21.5%) were the common forms of abuse reported. CONCLUSION: IPV is common among HIV positive pregnant Nigerians; with a threefold increased risk in women in HIV serodiscordant relationship.

Sero-prevalence and factors associated with Hepatitis B and C co-infection in pregnant Nigerian women living with HIV infection.

INTRODUCTION: Perinatal and horizontal transmission of Hepatitis B occur in areas of high endemicity as most infections are acquired in the first 5 years of life. Unless Hepatitis B and C infected pregnant women identified, and appropriate treatment provided, children born to these women are at high risk of chronic Hepatitis B (and C) virus infection. The objecive of this study was to determined the prevalence and the factors associated with Hepatitis B and C Virus infection in pregnant HIV positive Nigerians. METHODS: A cross sectional study among HIV Positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women were screened for Hepatitis B and C Virus infection at enrollment. HIV viral load, CD4 count, liver transaminases and hemoglobin levels were also determined. Data were managed with SPSS for windows version. Ethical approval was obtained from the Institutions Ethical Review Board. RESULTS: Of the 2391 studied subjects, 101(4.2%) and 37(1.5%) respectively were seropositive for Hepatitis B and C Virus infection. Twowomen (0. 08%) had triple infections. blood transfusion, (cOR: 2.3; 95% CI:1.1-4.6), history of induced abortion (cOR:2. 2;95% CI:1.3-3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2. 2;4.2) were significantly associated with HBV. History of induced abortion was the only factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9). CONCLUSION: Hepatitis B Virus infection (4.2%) is relatively common in our environment and associated with induced abortion, blood transfusion and elevated baseline transaminase. Hepatitis C Virus infection (1.5%) is less common and associated with only history of induced abortion.

Pattern, challenges and correlates of condom use among Nigerians living with HIV infection.

OBJECTIVE: To determine the pattern, challenges and correlates of condom use among Nigerians living with HIV Infection. METHODS: A cross sectional questionnaire study among HIV positive adults attending an HIV treatment centre in Lagos, Nigeria. Data entry and analysis were done with Epi-info version 3.5.1. RESULTS: The mean age of respondents was 35 (SD=7.7; range: 17-58 years) and mean age at sexual debut was 20 years old (range: 7-37 years). Majority were women (66.6%), had at least secondary school education(91.1%), married (68.2%)), on ART (50.7%) and knew their partners HIV status(60.9%). The rate of condom use at last sex act was 65.9%, but only 48.8% used condom consistently. Factors associated with condom use were male gender (OR=2.43, CI=1.35-4.33, P=0.002), less than secondary school education (OR=3.12, CI=1.04-9.28, P=0.05) and Not knowing partner's HIV status (OR=1.90, CI=1.04-3.80, P=0.04). Refusal to use condom (28.4%) were as a result of pregnancy intention, undesirability of condom in marriage and decreased sexual pleasure. CONCLUSION: There is low consistent condom use rate of 48.8% among this cohort despite their exposure to behavioural change messages. A review of the present counselling strategy and combination prevention is therefore advocated.

Sputum smear concentration may misidentify acid-fast bacilli as Mycobacterium tuberculosis in HIV-infected patients.

BACKGROUND: Tuberculosis (TB) diagnosis in most resource-limited settings still depends on smear microscopy for identification of acid-fast bacilli (AFB). However, recently developed molecular diagnostics that test for the presence of Mycobacterium tuberculosis (Mtb) DNA have been shown to be superior for confirmation of TB diagnosis. METHODS: At regular clinical visits over a 12-month period, we collected sputa from HIV-infected patients presenting with signs or symptoms of TB at 2 Nigerian clinics. Sputa were stained for AFB and tested using the Genotype MTBDRplus to confirm the presence of Mtb. Other species were identified using 16S rRNA sequence. RESULTS: In 56% (233/415) of AFB-positive patients, Mtb was confirmed. The patients on antiretroviral therapy were less likely than those not on antiretroviral therapy to be infected with Mtb [odds ratio (OR) = 0.25, P = 0.003]. In a multivariate logistic regression model using clinical features and diagnostic results, abnormal respiratory findings on auscultation (OR = 3.28, P = 0.03) and a direct sputum smear grade >3/100 (OR = 6.4, 4.6, P < 0.02) were significant predictors of Mtb infection. Concentrated sputum smear was predictive of Mtb infection only at the highest grades (2+, 3+). Interestingly, among 65 samples that could not be confirmed for Mtb, 32 (49%) were found to contain other, possibly novel, actinomycetes, including atypical Mycobacteria, Rhodococcus spp, Nocardia spp, and Corynebacterium spp. CONCLUSIONS: We conclude that concentrated sputum smears may misidentify other bacteria as Mtb in HIV-infected patients. The use of molecular diagnostics could reduce unnecessary or inappropriate treatment and improve identification of pathogens in resource-limited settings with high HIV burden.

Management of HIV-1 infection with a combination of nevirapine, stavudine, and lamivudine: a preliminary report on the Nigerian antiretroviral program.

OBJECTIVE: To evaluate treatment outcome in the first 12 months among HIV-positive patients managed with a combination of nevirapine + stavudine + lamivudine under the current national antiretroviral (ARV) program in Nigeria. DESIGN: This was a prospective observational, cohort study on 50 ARV-naive patients who met the inclusion criteria for the program and had given informed consent. All patients were in stage 2 or stage 3 periods of infection based on World Health Organization clinical classification. The patients were treated with the generic brands of ARVs and treatment consisted of oral nevirapine (Nevimal, Cipla, Mumbai, India), 200 mg daily, lamivudine (Lamivir, Cipla), 150 mg twice daily, and stavudine (Stavir, Cipla), 40 mg twice daily. Prior to initiation of treatment, the clinical history and baseline data for each patient were documented. The levels of plasma HIV-1 RNA, CD4 cell counts, frequency of opportunistic infections, and estimated body mass index were recorded at baseline and subsequently at intervals during treatment. Data obtained at the various sampling times for each parameter were compared against their baseline values. RESULTS: Data on the plasma HIV-1 RNA levels indicated that between baseline and week 24, the median viral load of the patients decreased by 1.79 log(10) copies/mL. Equally between baseline and week 48 the median CD4 cell counts increased by 186 x 10(6) cells/L, the frequency of opportunistic infections decreased by 82%, the median body mass index increased by 4.8 kg/m(2), and 36% experienced side effects, which were minor and transient. The most prevalent side effect recorded was skin rash associated with nevirapine. Good adherence to this triple regimen was recorded in >85% of the patients. CONCLUSIONS: The overall results within the 12-month treatment period indicated an effective suppression of viral replication, the reconstitution of the immune system, and improvement of the physical well-being of the study population. Though there may be differences in global distribution of the infecting HIV-1 subtypes, the clinical and biologic results of this study compared favorably to those documented in cohorts treated with branded and generic ARV drugs in some developed and developing countries. The cumulative data in this study further confirmed that the correct use of generic brands of ARVs is a feasible option in HIV care and support programs in resource-poor countries.