Assessing the relationship between HIV infection and cervical cancer in Côte d'Ivoire: a case-control study.

BACKGROUND: The association between HIV infection and invasive cervical cancer that has been reported may reflect differential prevalence of human papillomavirus (HPV) infection or uncontrolled confounding. We conducted a case-control study in a West African population to assess the relationship between HIV infection and invasive cervical cancer, taking into account HPV infection and other potential risk factors for cervical cancer. METHODS: Women with invasive cervical cancer (cases) or normal cervical cytology (controls) were recruited in a hospital-based case-control study in Abidjan, Côte d'Ivoire. Odds ratios and 95% confidence intervals (CI) were estimated in logistic regression analyses controlling for important cofactors. RESULTS: HIV infection was noted in 22/132 (16.7%) cases and 10/120 (8.3%) controls (p = 0.048). High-risk HPV infection was detected in cervical tumor samples from 89.4% of case-participants and in cervical cytology samples in 31.1% of control-participants. In logistic regression analysis, HIV infection was associated with cervical cancer in women with HPV (OR 3.4; 95% CI 1.1-10.8). Among women aged 2 (OR 7.0; 95% CI 1.9-25.7) and HIV infection (OR 4.5; 95% CI 1.5-13.6). Among women aged > 40 years, high-risk HPV infection (OR 23.5; 95% CI 9.1-60.6) and parity > 2 (OR 5.5; 95% CI 2.3-13.4), but association with HIV infection was not statistically significant. CONCLUSIONS: These data support the hypothesis that HIV infection is a cofactor for cervical cancer in women with HPV infection, and, as in all populations, the need for promoting cervical screening in populations with high prevalence of HIV infection.

Quantification of HIV-1 p24 by a highly improved ELISA: an alternative to HIV-1 RNA based treatment monitoring in patients from Abidjan, Côte d'Ivoire.

BACKGROUND: Quantification of HIV-1 RNA remains difficult to implement in Africa. Simple and inexpensive tests for antiretroviral treatment (ART) monitoring are needed. OBJECTIVE: To evaluate an HIV-1 p24 ELISA, which combines efficient virus disruption, heat-denaturation and signal amplification, in a West African setting. STUDY DESIGN: Eighty-six HIV-1 infected patients from Abidjan, Côte d'Ivoire, were tested for p24, HIV-1 RNA, and CD4+ count at baseline, and twice within 8 months after ART initiation. RESULTS: All patients responded to ART with a minimal HIV-1 RNA drop of 0.5 log(10) at first follow-up. Forty-one (47.7%) then rebounded >0.5 log(10) or persisted above 1000 copies/mL by week 24. The predicted baseline concentration of p24 corresponding to 100,000 copies/mL of HIV-1 RNA, above which ART is recommended, was 4546 fg/mL (95% confidence interval 3148-6566). A prediction model of virologic failure, occurring after an initial response to ART, correctly classified 84% of patients using baseline p24, p24 change on therapy, and achievement of undetectable p24 as explanatory variables. The model and further bootstrap evaluation suggested a good ability to discriminate between sustained or failing virologic response to ART. CONCLUSION: HIV-1 p24 and RNA based-ART monitoring in a low-resource country dominated by HIV-1 CRF02 AG appeared comparable.

Measurement of HIV-1 CRF02_AG-specific T cell responses indicates the dominance of a p24gag epitope in blood donors in Abidjan, Cote d'Ivoire.

Characterization of human immunodeficiency virus (HIV)-1-specific immune responses against subtypes circulating in areas where the virus is endemic is critical for the design of candidate vaccines. In Cote d'Ivoire, the most prevalent HIV-1 subtype is CRF02_AG. We detected T cell responses to CRF02_AG consensus p24(gag) or protease peptides in 81% of HIV-1- or HIV-1/2-infected blood donors in Abidjan, Cote d'Ivoire. Both the magnitude and the breadth of interferon- gamma enzyme-linked immunospot responses were inversely correlated with plasma viral load. One frequently recognized peptide in p24(gag) was mapped to the optimal epitope (TPQDLNMML). Further studies of this epitope may be important for the development of HIV-1 vaccines for West Africa and West-Central Africa.

Changes in HIV RNA viral load, CD4+ T-cell counts, and levels of immune activation markers associated with anti-tuberculosis therapy and cotrimoxazole prophylaxis among HIV-infected tuberculosis patients in Abidjan, Cote d'Ivoire.

We analyzed changes in plasma human immunodeficiency virus (HIV)-1 viral load, CD4+ T-cell count, and markers of immune activation markers at start of treatment of tuberculosis and 12 months after among 44 HIV-1-infected patients with newly diagnosed, sputum-smear positive for Mycobacterium tuberculosis pulmonary infection. All patients received a standard regimen of 6 months of rifampicin and isoniazid with first 2 months of pyrazinamid with or without cotrimoxazole. Compared with values at start of treatment, median viral load increased by a median of 0.64 log10 copies/ml after 12 months of follow-up (P=0.0002). Median CD4+ T-cell counts were 393 cells/L at start of treatment and 370 cells/L after 12 months of follow-up (P=0.61). Levels of serum activation markers decreased significantly at 12 months of follow-up of the patients for both patients on standard and cotrimoxazole treatment. Levels of viral load, CD4+ T-cell counts, and markers of immune activation were not different for patients on standard treatment of tuberculosis compared with those on standard and cotrimoxazole treatment. Levels of serum activation markers decreased significantly at 12 months of follow-up of the patients for both patients on standard and cotrimoxazole treatment. Because viral load is a predictor of disease progression, its persistent elevated levels in blood of HIV-infected patients co-infected with tuberculosis, who successfully complete TB treatment, may account for the high mortality observed in this population.

HIV-specific T helper responses and frequency of exposure among HIV-exposed seronegative female sex workers in Abidjan, Cote d'Ivoire.

BACKGROUND: The characteristics of human immunodeficiency virus (HIV) exposure that determine the induction of HIV-specific T cells and, in particular, T helper cells are not well understood. METHODS: HIV-1 Gag- and Env-specific T helper cells were analyzed by use of an interferon (IFN)- gamma enzyme-linked immunosorbent spot (ELISPOT) assay and by use of IFN- gamma secretion flow cytometry. Responses among HIV-exposed seronegative (ESN) female sex workers (FSWs) were compared with responses among HIV-seropositive FSWs and HIV-seronegative female blood donors from Abidjan, Cote d'Ivoire. RESULTS: Low-level ELISPOT responses were detected in 8 (20%) of 40 ESN FSWs. All of 25 HIV-seropositive FSWs had high-level ELISPOT responses. HIV-specific CD4+ T cells and, occasionally, CD8+ T cells were detected by secretion flow cytometry in 3 (38%) of 8 ESN FSWs and in 4 (80%) of 5 HIV-seropositive FSWs. ESN FSWs with detectable HIV-specific T helper responses had more clients on the previous working day (P=.02) and more exposures to HIV per month (P=.02) and tended to have a lower total duration of commercial sex work. CONCLUSIONS: These findings demonstrate that the presence of HIV-specific T helper cells in ESN FSWs is associated with the frequency, rather than the duration, of exposure to HIV. The data may have important implications for the evaluation of HIV vaccine efficacy.

Medium-term survival, morbidity and immunovirological evolution in HIV-infected adults receiving antiretroviral therapy, Abidjan, Côte d'Ivoire.

OBJECTIVES: To evaluate survival, morbidity, and CD4 and viral load (VL) evolution in HIV-infected adults receiving antiretroviral therapy (ART) in Côte d'Ivoire. METHODS: Since 1996, 723 HIV-infected adults have been followed up in the ANRS 1203 cohort study in Abidjan. For those patients who received ART, we describe data between ART initiation and August 2002. RESULTS: One-hundred-and-one adults (61% women) were followed up under ART for a median of 17 months. At ART initiation, median age, CD4 count and VL were 36 years, 135/mm3 and 5.3 log10 copies/ml, respectively. Initial ART regimens were two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor in 74 patients, two NRTIs plus one non-nucleoside reverse transcriptase inhibitor in 16, and two NRTIs in 11. No patient was lost to follow-up. The most frequent causes of severe morbidity were bacterial infections [11.6/100 person-years (PY), 95% CI: 7.2-18.7], drug-related events (6.5/100 PY, 3.5-12.0), tuberculosis (3.1/100 PY, 1.3-7.4) and malaria (3.1/100 PY, 1.3-7.4). The incidence of death was 3.0/100 PY (1.1-8.0) in patients with baseline CD4 > or = 50/mm3 and 16.1/100 PY (7.2-35.9) in patients with CD4 < 50/mm3. Fifty percent of causes of death were active infections pre-existing ART initiation, mainly atypical mycobacteriosis. After 1 year, 51% of patients had undetectable VL, 28% had detectable VL reduced by more than 0.5 log10 copies/ml since ART initiation, and the median gain in CD4 was +115/mm3. CONCLUSION: Medium-term survival under ART may be as good in Africa as in industrialized countries, provided that patients benefit from access to care for opportunistic infections, including bacterial diseases, tuberculosis and malaria.

Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Côte d'Ivoire.

BACKGROUND: In Côbte d'Ivoire, a pilot project was developed by UNAIDS and the Ministry of Health to improve access to AIDS care, including antiretroviral therapy, for adults and children infected with HIV. This evaluation of the project is the first to provide results of a large number of HIV-infected patients receiving antiretroviral therapy in West Africa. METHODS: We evaluated records of persons who presented for care from August 1998 to August 2000 at six accredited centers in Abidjan. Patients were treated with two nucleoside reverse transcriptase inhibitors (2NRTI) or highly active antiretroviral therapy (HAART). RESULTS: Of 2878 patients who were screened, 2351 (83%) were HIV-infected and eligible (CD4 T lymphocyte count < 500 x 10(6) cells/l or plasma HIV-RNA level > 10 000 copies/ml) for antiretroviral therapy. Of those who were eligible, 81% were symptomatic, 63% had a CD4 cell count < 200 x 10(6) cells/l, 12% had previously taken antiretroviral drugs, and 56% returned to the clinic for follow-up. Of the patients screened, 768 (27%) were started on antiretroviral therapy, including 450 on HAART, 296 on 2NRTI, and 22 on other regimens. We analyzed data from 480 HIV-1-infected adults, who were naive to therapy, were prescribed HAART or 2NRTI, and had at least one clinic visit after starting therapy. In an intent-to-treat analysis of patients who received HAART, the estimated plasma HIV-1 RNA level was approximately 1.9 log10 copies/ml (80-fold) lower, while estimated CD4 cell count was > 100 x 10(6) cells/l higher than baseline values, after 1 year of therapy. Approximately 25% of adults on 2NRTI and 50% of those on HAART had < 200 copies/ml, after 1 year of therapy. The probability of an adverse event occurring within 6 months after starting therapy was 0.20. The probability of survival for at least 1 year was 0.84 (95% confidence interval, 0.80-0.89). CONCLUSION: After starting antiretroviral therapy, these HIV-1-infected patients in West Africa had similar virologic and immunologic outcomes, probability of an adverse event, and estimated survival, as patients enrolled in clinical trials in the USA and Europe. However, only one-third of eligible patients received therapy, highlighting the importance of providing adequate education and support for initiating and adhering to therapy in this and similar programmes.

Changes in levels of immune activation and reconstitution markers among HIV-1-infected Africans receiving antiretroviral therapy.

OBJECTIVE: To describe changes in immune activation and reconstitution markers among HIV-1-infected patients receiving antiretroviral therapy (ART) in Abidjan, Côte d'Ivoire. METHODS: Between November 1998 and February 2001, we analyzed changes in immune activation and reconstitution markers among 52 patients. Good virologic responders (n = 26) were defined as those who had suppressed and maintained plasma viral load (VL) below the detection limit of the assay for at least 12 months. Poor virologic responders (n = 26) were defined as those with a detectable VL at 6 and 12 months after beginning ART. RESULTS: Of the 26 good virologic responders, 20 (77%) were on highly active antiretroviral therapy (HAART) compared with one (4%) of the poor responders. Among the 26 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Median levels of HLA-DR+CD8+ T cells also decreased from baseline at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ T cells increased steadily during the 6 and 12 months of therapy and reached levels observed among HIV-negative blood donors (P = 0.07). Among the 26 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 12 months of therapy (P = 0.006), but were higher than levels in blood donors (P = 0.005). Levels of HLA-DR+CD8+ T cells decreased significantly at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ decreased over time. CONCLUSION: Our results suggest that HAART can be successfully used in African populations with elevated baseline immune activation markers.

Antiretroviral therapy in HIV-2-infected patients: changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of patients treated in Abidjan, Côte d'Ivoire.

OBJECTIVE: To describe changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of HIV-2-infected patients receiving antiretroviral (ARV) therapy in Abidjan, Côte d'Ivoire. METHODS: Consecutive blood samples were collected from 18 HIV-2-infected ARV-naive patients who had received ARV therapy in the UNAIDS drug access initiative (UNAIDS-DAI) in Abidjan between August 1998 and July 2000. Changes in HIV-2 plasma viral load, CD4+ cell counts, and genotypic and phenotypic drug resistance testing were determined. RESULTS: At baseline, 11 (61%) of the 18 patients initiated highly active antiretroviral therapy (HAART) and seven (39%) received dual therapy. No significant change in median viral load was observed at 2 months (P = 0.09), at 6 months (P = 0.06), and at 12 months of therapy (P = 0.26). No significant increase in CD4+ cell counts was observed at 12 months (P = 0.10). All four patients on indinavir-containing HAART had undetectable viral loads at 2-4 months of therapy. However, none of seven patients on nelfinavir-containing HAART had a substantial decrease in viral load. Viruses from 14 patients were analyzed, 12 of which (86%) had at least one primary resistance mutation that is known to confer resistance to HIV-1 virus. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine. CONCLUSION: Our limited findings show that nelfinavir-containing regimens may have limited virologic benefit to HIV-2-infected patients.

The most efficient use of resources to identify those in need of antiretroviral treatment in Africa: empirical data from Côte d'Ivoire's Drug Access Initiative.

OBJECTIVE: To describe the cost and outcome associated with the use of CD4 cell count and viral load tests as part of screening strategies to identify persons eligible for subsidized antiretroviral therapy (ART) in Côte d'Ivoire. METHODS: Empirical data from the Drug Access Initiative in Côte d'Ivoire (DAI-CI) were used to describe the laboratory cost of patient screening using sequential clinical staging, CD4 cell count, and viral load and the proportion of screened patients identified as eligible for ART. We also estimated costs modelling a parallel screening algorithm, across a range of laboratory costs and with current international recommendations to assess treatment eligibility. Benefit was defined as being found eligible for ART. RESULTS: Of the 2138 HIV-positive, ART-naive, adults who presented to the DAI-CI between July 1998 and July 2000, median CD4 cell count was 172 x 10(6) cells/microl. DAI-CI criteria identified 2057 (96%) of these persons eligible for antiretroviral treatment. In a serial screening algorithm, 75% were eligible by CDC clinical stage B or C; 18% by CD4 cell count less than 500 x 10(6) cells/microl; and an estimated 3.9% by a viral load greater than 10 000 copies/ml. Use of the current US recommendations and a serial algorithm would have resulted in 1977 (92%) persons eligible for ART: 75% by CDC clinical stage B or C; 15% by CD4 cell count less than 350 x 10(6) cells/microl (including 8% < 200 x 10(6) cells/microl); and an estimated 3.6% due to viral load greater than 55 000 copies/ml. Using DAI-CI criteria and heavily subsidized laboratory test costs, the addition of CD4 cell count to clinical criteria cost US dollar 50 (serial algorithm) and US dollar 203 (parallel algorithm) to identify each additional eligible person. Modelling current recommendations with a serial algorithm, CD4 cell count cost an average US dollar 62/eligible person (US recommendations) and US dollar 109 (WHO recommendations). The addition of viral load cost between US dollar 108 (serial algorithm DAI) to US dollar 1700 (parallel algorithm DAI) to identify each additional eligible person. CONCLUSION: In the African context of scarce resources and the huge unmet demands for voluntary HIV testing and for ART, simple screening strategies are needed to identify those most in need of ART. Health personnel should be trained to identify and refer clinically symptomatic persons. Viral load testing is of high cost and dubious benefit and should not be part of screening algorithms for initiating ART.

HIV prevalence and risk behavior among clients of female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To assess socio-demographic and behavioural characteristics of clients of female sex workers in Abidjan, and to determine their HIV prevalence and related risk factors. DESIGN: A cross-sectional study among clients of female sex workers in Abidjan, Côte d'Ivoire. METHODS: A trained interviewer approached clients leaving the room of a female sex worker and invited them for an interview using a structured questionnaire, and to provide a saliva sample. Saliva was tested for HIV antibodies by the GACELISA assay (Murex, Dartford, UK). RESULTS: A total of 526 clients agreed to participate, and 423 (80.4%) provided a saliva sample. Reported condom use was very high, 92.7% said they always use condoms and 95.4% reported condom use during the visit preceding the interview. The overall HIV prevalence among the clients who provided a saliva sample was 13.4%. Older age and being married or cohabitating was significantly associated with HIV infection in multivariate analysis. CONCLUSIONS: HIV prevalence appears to be relatively low, and condom use is high among clients of female sex workers in Abidjan. Existing HIV prevention efforts among female sex workers and among the general population should be sustained and reinforced.

Assessment of the validity of and adherence to sexually transmitted infection algorithms at a female sex worker clinic in Abidjan, Côte d'Ivoire.

BACKGROUND: Algorithms for sexually transmitted infection (STI) case management were designed in a female sex worker (FSW) clinic in Abidjan, Côte d'Ivoire, in 1993. GOAL: The goal was to evaluate the long-term validity of the algorithms for returning clients of the clinic and to assess the adherence of the health workers to their application. STUDY DESIGN: A cross-sectional study was conducted from 1999 to 2000 among FSWs attending as returning clients. RESULTS: The prevalences of genital infections were as follows: Neisseria gonorrhoeae and/or Chlamydia trachomatis, 8.2%; Trichomonas vaginalis, 16.7%; bacterial vaginosis, 62.3%; and Candida albicans, 6.2%. The sensitivity of the algorithms was 20% and the positive predictive value was 14% for cervical infection. The proportion of cases for which all steps of the algorithm were correctly applied was 30%. CONCLUSION: Algorithms for the treatment of STIs in FSWs should be periodically reevaluated and adapted to the changing population. To maintain healthcare workers' adherence to the algorithms, supervision should be ongoing and reinforced.

Cellular human immunodeficiency virus (HIV)-protective factors: a comparison of HIV-exposed seronegative female sex workers and female blood donors in Abidjan, Côte d'Ivoire.

Cellular factors that may protect against human immunodeficiency virus (HIV) infection were investigated in 27 HIV-exposed seronegative (ESN) female sex workers (FSWs) and 27 HIV-seronegative female blood donors. Compared with blood donors, ESN FSWs had significantly decreased expression levels of C-X-C chemokine receptor 4 (CXCR4), but not of C-C chemokine receptor 5, on both memory (P<.001) and naive (P=.041) CD4(+) T cells. CXCR4 down-regulation was associated with prolonged duration of commercial sex work by ESN FSWs. CD38 expression on CD8(+) T cells was significantly increased among ESN FSWs, compared with that among blood donors (P=.017). There were no differences in HLA-DR and CD62L expression between blood donors and ESN FSWs. Proportions of T cells producing the beta-chemokines RANTES (regulated on activation, normally T cell-expressed and -secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta or the cytokines interleukin (IL)-2, IL-4, interferon-gamma, and tumor necrosis factor-alpha, were similar in the 2 groups. These data indicate that ESN FSWs differ from HIV-seronegative female blood donors with respect to immunological factors that have no clear protective potential against HIV transmission.

Changes in plasma HIV-1-RNA viral load and CD4 cell counts, and lack of zidovudine resistance among pregnant women receiving short-course zidovudine.

OBJECTIVE: To describe changes in HIV-1 plasma viral load (VL) and CD4 cell counts and to assess zidovudine resistance associated with a short course of oral zidovudine during late pregnancy. METHODS: From April 1996 to February 1998 in Abidjan, Côte d'Ivoire, 280 HIV-1-seropositive women were randomly assigned at 36 weeks' gestation to receive zidovudine (300 mg) or placebo twice a day, and then one tablet every 3 h from the onset of labor until delivery. Blood samples obtained every 2 weeks until delivery, then at 2 and 4 weeks, and 3 or 6 months after delivery were tested from selected women based on duration of therapy for plasma VL and CD4 cell counts, and samples from 20 women in the zidovudine group were tested by DNA sequencing for the presence of zidovudine resistance mutations. RESULTS: In the zidovudine group, the median reduction in plasma VL (log(10) copies/ml) was -0.48 after 2 weeks (P = 0.02 versus placebo), -0.48 after 4 weeks (P = 0.06), -0.80 after 6 weeks (P = 0.29) of treatment, -0.12 at delivery (P = 0.11), +0.21 at 2 weeks (P = 0.83), +0.17 at 4 weeks (P = 0.69), and +0.21 at 3 months (P = 0.56) postpartum. Median CD4 cell counts were higher in the zidovudine than in the placebo group after 2, 4, and 6 weeks of treatment (P < 0.05). No mutations associated with zidovudine resistance were identified in any of the samples tested. CONCLUSION: These findings suggest that a short course of zidovudine has no adverse HIV-1 virological consequences for the mother.

Positive association between beta-chemokine-producing T cells and HIV type 1 viral load in HIV-infected subjects in Abidjan, Côte d'Ivoire.

The role of beta-chemokines in controlling HIV replication in vivo is still controversial. Therefore, the association between HIV-1 plasma viral load and the capacity of CD4(+) and CD8(+) T cells to produce beta-chemokines was studied in 28 antiretroviral drug-naïve HIV-1-infected female sex workers in Abidjan, Côte d'Ivoire. Percentages of beta-chemokine-positive T cells were measured in peripheral blood mononuclear cells by flow cytometry after intracellular staining for RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. HIV-1-infected subjects had higher percentages of MIP-1alpha- and MIP-1beta-positive CD4(+) and CD8(+) T cells (p < 0.02) and of RANTES-positive CD8(+) T cells (p = 0.054) than uninfected controls. Percentages of RANTES- and MIP-1beta-positive CD8(+) T cells correlated directly with HIV-1 plasma viral load (p < 0.02). Percentages of beta-chemokine-positive CD4(+) and CD8(+) T cells correlated directly with percentages of HLA-DR-positive T cells (p < 0.02) and inversely (except RANTES in CD4(+) T cells) with absolute numbers of CD4(+) T cells (p < 0.05) in peripheral blood. These data indicate that increased percentages of beta-chemokine-producing T cells in HIV-1-infected subjects correlate with disease progression and are a sign of viremia-driven chronic T cell activation.