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1.
J Int Assoc Provid AIDS Care ; 23: 23259582241238653, 2024.
Article in English | MEDLINE | ID: mdl-38509798

ABSTRACT

BACKGROUND: Identifying patterns in the distribution of new HIV infections in the population is critical for HIV programmatic interventions. This study aimed to determine the distribution of New HIV infection by applying the incidence patterns mathematical model to data from Lagos state. METHODS: The incidence patterns model (IPM) software is a mathematical model developed by UNAIDS to estimate the demographic and epidemic patterns of HIV infections. This model was adapted in Lagos state to predict the distribution of new HIV infections among specified risk groups in the next 12 months. RESULTS: The IPM predicted a total HIV incidence of 37 cases per 100 000 individuals (3979 new infections) will occur among the 15 to 49 subpopulations. The results also showed that sero-concordant HIV-negative couples with external partners (29%), female sex workers (26%), men-having-sex-with-men (18%), and previously married females (6%) accounted for the majority of the estimated new HIV infections. Overall, key populations constitute almost half (48%) of the estimated number of new HIV infections. CONCLUSION: The study helped to identify the population groups contributing significantly to new HIV infections. Therefore, priority interventions should be focused on these groups.


Subject(s)
HIV Infections , Sex Workers , Male , Humans , Female , HIV Infections/epidemiology , Nigeria/epidemiology , Incidence , Risk Factors
2.
Contraception ; 80(5): 484-92, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19835725

ABSTRACT

BACKGROUND: The objectives of this clinical trial were to evaluate the safety, tolerance and acceptability of two gel formulations of the Invisible Condom: (i) the polymer alone and (ii) the polymer-containing sodium lauryl sulfate (SLS) compared to placebo when applied intravaginally with our unique applicator in sexually abstinent and active woman volunteers. STUDY DESIGN: A randomized, doubled-blind, placebo-controlled study in healthy women from Yaoundé, Cameroon. Two hundred sixty women were randomized into three gel arms: (a) gel alone, (b) gel plus SLS and (c) placebo gel. Thirty-seven sexually abstinent women applied gel intravaginally once a day for 14 days, while 75, 74 and 74 sexually active women applied gel intravaginally once, twice or three times daily for 14 days, respectively. RESULTS: Retention rate was high at 85% and 221 women applied the two products and the placebo for a total of 6005 times. Nugent score, H(2)O(2)-producing lactobacilli and vaginal pH were stable throughout the study and were not affected by the study products. Colposcopy showed neither genital ulceration nor mucosal lesions. No study product-related serious adverse events were reported. The majority of reported adverse events were mild or moderate and largely similar in all 3 arms. Satisfaction questionnaire showed that the gel formulations and applicator were generally comfortable and acceptable. CONCLUSION: The Invisible Condom formulations and applicator were found to be comfortable, well tolerated and acceptable when applied intravaginally once, twice or thrice daily for 14 days. Thus, expanded safety evaluation is warranted.


Subject(s)
Anti-Infective Agents , Cervix Uteri/pathology , Patient Satisfaction/statistics & numerical data , Poloxalene , Sodium Dodecyl Sulfate , Vagina/microbiology , Adolescent , Adult , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Cameroon , Cohort Studies , Double-Blind Method , Female , Gels/administration & dosage , Gels/adverse effects , Humans , Middle Aged , Poloxalene/administration & dosage , Poloxalene/adverse effects , Prospective Studies , Sexual Partners/psychology , Sexually Transmitted Diseases/prevention & control , Sexually Transmitted Diseases/transmission , Sodium Dodecyl Sulfate/administration & dosage , Sodium Dodecyl Sulfate/adverse effects , Surveys and Questionnaires , Vagina/pathology , Vaginal Creams, Foams, and Jellies/administration & dosage , Vaginal Creams, Foams, and Jellies/adverse effects , Young Adult
3.
J Acquir Immune Defic Syndr ; 49(4): 432-9, 2008 Dec 01.
Article in English | MEDLINE | ID: mdl-18931623

ABSTRACT

OBJECTIVE: The HIV epidemic in Cameroon is characterized by a high level of strain diversity despite a relatively low prevalence of infection. In this study, HIV strains infecting blood donors in Cameroon were characterized to determine the prevalence of subtypes and intersubtype recombinants and if strain prevalence was changing over time. METHODS: From 1996 through 2004, 676 HIV-infected blood donations were collected at blood banks in Douala and Yaoundé, Cameroon. A subset of the HIV-1 group M strains (n = 574) were classified based on phylogenetic analysis of viral sequences from the gag p24, pol integrase, and env gp41 regions. RESULTS: HIV-1 group M accounted for 97.3% (n = 658) of infections, whereas group O was present in 2.2% (n = 15) and HIV-2 in 0.4% (n = 3). Within the group M infections, 14 subtypes and circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified. Overall, CRFO2_AG accounted for 58.2% of infections, URFs 14.8%, and levels of subtypes, A, B, C, D, F2, and G, and CRFs, 01, 06, 09, 11, 13, 22, and 37, varied from 0.2% to 6.1%. Evaluation of HIV strains present in the donor population over this 9-year period showed no substantial changes in the proportion of infections caused by each subtype and CRF, the percentage of intersubtype recombinants, or the strain composition of the URFs. CONCLUSIONS: HIV-1 strain diversity in Cameroon did not significantly change, suggesting a mature and relatively stable epidemic.


Subject(s)
Blood Donors , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/genetics , Phylogeny , Cameroon/epidemiology , HIV-1/classification , Humans , Molecular Sequence Data , Prevalence , Time Factors
4.
Pan Afr Med J ; 1: 2, 2008 Jul 04.
Article in English | MEDLINE | ID: mdl-21532891

ABSTRACT

BACKGROUND: Retention in long-term antiretroviral therapy (ART) program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART) discontinuation raises concerns about drug resistance and could negate much of the benefit sought by ART programs. METHODS: Based on existing patient records, we assessed determinants of retention in HIV care among HIV patients enrolled in an urban ART at two urban hospitals in Cameroon. Extended Cox regression procedures were used to identify significant predictors of retention in HIV care. RESULTS: Of 455 patients, 314 (69%) were women, median (IQR) age and baseline CD4 cell count were respectively 36 years (30 - 43) and 110 cells/µL (39 - 177). Forty patients (9%) had active tuberculosis (TB) at enrollment. After a median (IQR) follow-up of 18 months (10-18), 346 (75%) were still in care, 8 (2%) were known dead, and 101 (22%) were lost to follow-up (LFU). Severe immunosuppression (CD4 cell count ≤ 50 cells/µL) at baseline (aHR 2.3; 95% CI 1.4 - 3.7) and active tuberculosis upon enrollment (aHR 1.8; 95% CI 1.0 - 3.6) were independent predictors of cohort losses to follow-up within the first 6 months after HAART initiation. CONCLUSION: These data suggest that three-quarter of HIV patients initiated on HAART remained in care and on HAART by 18 months; however, those with compromised immunologic status at treatment initiation, and those co-infected with TB were at increased risk for being lost to follow-up within the first 6 months on treatment.

5.
AIDS Res Hum Retroviruses ; 22(10): 936-44, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17067262

ABSTRACT

The Nef protein of human immunodeficiency virus type 1 (HIV-1) has multiple functional domains, is immunogenic, and contains several cytotoxic T lymphocyte (CTL)-targeted epitopes. Several defined subfunctions of Nef are important for the pathogenesis of HIV-1 infection. In this study, we present the genetic diversity of the nef gene of 55 newly derived HIV-1 sequences obtained from Cameroonian patients. Four genetic subtypes and three circulating recombinant forms (CRFs) were identified: subtypes A (11%), G (7.3%), D (5.4%), F1 (1.8%), F2 (5.4%), CRF01_AE (5.4%), CRF02_AG (58.2%), and CRF11_cpx (1.8%). Two isolates clustered distinctly from the known HIV-1 genetic subtypes in nef and were designated as unclassified. Interestingly, the majority of all functional domains including the myristoylation signal, CD4 binding motif, beta turn motif, and the phosphorylation sites were well conserved in our cohort. Putative CTL-epitopic domains of the central portion of Nef were also well conserved, whereas those at the C-term were not. Our study demonstrated that despite high genetic diversity observed in the nef gene, most described functional domains and CTL epitopes were well conserved among Cameroonian HIV-1 subtypes. These findings could be used for the development of antiretroviral-acting therapeutics and anti-HIV-1 vaccines.


Subject(s)
Gene Products, nef/genetics , Adult , Amino Acid Sequence , Cameroon , Female , Genetic Variation , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Prospective Studies , Protein Structure, Tertiary , Sequence Alignment , nef Gene Products, Human Immunodeficiency Virus
6.
Antivir Ther ; 11(5): 575-9, 2006.
Article in English | MEDLINE | ID: mdl-16964825

ABSTRACT

We analysed whether mutations associated with resistance to antiretroviral (ARV) drugs circulate among treatment-naive HIV-1-infected individuals at a period when these drugs started to become more widely available in Africa. Overall, major resistance mutations in the pol gene, as defined by the International AIDS Society Resistance Testing-USA panel, were observed in 16 treatment-naive individuals. Eight of the 97 patients tested in Burkina Faso bore mutations conferring resistance to one drug class of ARV drugs: two to nucleoside reverse transcriptase inhibitors (NRTIs; M41L [n = 1], M41L+T69S [n = 1]), four to non-NRTIs (NNRTIs; V106A/V [n = 1] and V1081 [n = 3]) and two to protease inhibitors (PIs; L33F [n = 2]). In Cameroon, resistance mutations were identified in 8 of 102 patients: three to PIs (M461/L [n = 2], L33F [n = 1]), three to NRTIs (T69N/T [n = 1], M184V [n = 1], A62V [n = 1]) and two to NNRTIs (P236L [n = 1], V1081 [n = 1]). It is important to note that not all genotypic drug-resistance algorithms give similar interpretations to the observed mutations. Population surveillance for ARV drug resistance is required and should be included in all implementation programmes.


Subject(s)
Drug Resistance, Multiple, Viral/genetics , HIV Infections/genetics , HIV Protease Inhibitors/therapeutic use , HIV-1/genetics , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Burkina Faso , Cameroon , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Protease/genetics , Humans , Male , Middle Aged , Mutation , National Health Programs , Population Surveillance , RNA-Directed DNA Polymerase/genetics
7.
AIDS Res Hum Retroviruses ; 22(8): 812-6, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16910839

ABSTRACT

To monitor the evolving molecular epidemiology and genetic diversity of HIV in a country where many distinct strains cocirculate, we performed genetic analyses on sequences from 75 HIV-1-infected Cameroonians: 74 were group M and 1 was group O. Of the group M sequences, 74 were classified into the following env gp41 subtypes or recombinant forms: CRF02 (n = 54), CRF09 (n = 2), CRF13 (n = 2), A (n = 5), CRF11 (n = 4), CRF06 (n = 1), G (n = 2), F2 (n = 2), and E (n = 1, CRF01), and 1 was a JG recombinant. Comparison of phylogenies for 70 matched gp41 and protease sequences showed inconsistent classifications for 18 (26%) strains. Our data show that recombination is rampant in Cameroon with recombinant viruses continuing to recombine, adding to the complexity of circulating HIV strains. This expanding genetic diversity raises public health concerns for the ability of diagnostic assays to detect these unique HIV mosaic variants and for the development of broadly effective HIV vaccines.


Subject(s)
DNA, Viral/genetics , Genetic Variation , HIV-1/genetics , Reassortant Viruses , Adult , Cameroon/epidemiology , Female , HIV Envelope Protein gp41/genetics , HIV Infections/epidemiology , HIV-1/classification , Humans , Male , Middle Aged , Molecular Sequence Data , Phylogeny , Reassortant Viruses/classification , Reassortant Viruses/genetics
8.
Emerg Infect Dis ; 12(6): 1001-4, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16707062

ABSTRACT

Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1/growth & development , Adult , Amino Acid Sequence , Base Sequence , Cameroon/epidemiology , Cross-Sectional Studies , Female , Genotype , HIV Infections/epidemiology , HIV-1/genetics , Humans , Male , Middle Aged , Phylogeny , RNA, Viral/chemistry , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Serotyping , Urban Population
9.
J Med Virol ; 78 Suppl 1: S22-3, 2006.
Article in English | MEDLINE | ID: mdl-16622873

ABSTRACT

Several diagnostic assays for the detection of HIV infection have been approved and licensed by the FDA for blood donor screening. However, the performance of these assays is unknown when testing genetically divergent blood specimens. To evaluate the performance of these assays with diverse HIV strains, we chose to study specimens collected from blood donors in Cameroon where genetic diversity and recombinant variants are prevalent. In this study, we tested 240 human plasma specimens collected from two blood centers in Cameroon. These samples were screened initially in Cameroon for antibody to HIV using a rapid assay. We also performed sequencing to determine subtype. Our evaluation has demonstrated that HIV infection in most HIV plasma samples could be detected by most of the US FDA licensed diagnostic assays. With the exception of a few specimens, HIV-1 p24 antigen was not detected in any of the samples. In addition, some nucleic acid tests (NAT) assays were not able to detect a few serologic reactive samples and all new variants including some CRF02_AG variants.


Subject(s)
Blood Donors , HIV Antibodies/blood , HIV Infections/diagnosis , HIV-1 , Licensure , Reagent Kits, Diagnostic/standards , United States Food and Drug Administration , Cameroon , False Negative Reactions , HIV Core Protein p24/analysis , HIV-1/genetics , HIV-1/immunology , Humans , RNA, Viral/analysis , Sensitivity and Specificity , United States
11.
AIDS Res Hum Retroviruses ; 21(5): 430-3, 2005 May.
Article in English | MEDLINE | ID: mdl-15929708

ABSTRACT

Recently T-20 or enfuvirtide, the first drug of a new class of antiretrovirals targeting the entry stage of the virus life cycle, has been clinically approved. Enfuvirtide is a peptide derived from the HR2 region of the transmembrane glycoprotein from the HXB2 HIV-1 subtype B prototype strain that binds to the HR1 region. Drug resistance seems to occur in the HR1 region between amino acids 36 and 45. We examined to what extent this region is conserved in 184 non-B strains from Cameroon: 132 (71.7%) CRF02-AG, 14 (7.6%) subtype A, 11 (5.9%) F2, 9 (4.8%) subtype D, 8 (4.3%) subtype G, 4 (2.1%) CRF01-AE, 4 (2.1%) CRF11-cpx, and 2 (1.1%) CRF06-cpx. Among the 184 strains studied, no amino acid mutation was found in the highly conserved three amino acid motif at codons 36-38 (GIV) that are important determinants of viral susceptibility to enfuvirtide. Other common substitutions like Q40H and N42T were also absent. The N42S polymorphism was present in 148 (80.4%) strains. Analysis of the HR2 domain, from which the peptide is derived, indicated a much greater genetic variability as compared to HR1.


Subject(s)
HIV Envelope Protein gp41/chemistry , HIV Envelope Protein gp41/metabolism , HIV Fusion Inhibitors/metabolism , HIV-1/metabolism , Peptide Fragments/metabolism , Amino Acid Sequence , Cameroon , Conserved Sequence , Enfuvirtide , HIV Envelope Protein gp41/genetics , HIV Envelope Protein gp41/pharmacology , HIV Fusion Inhibitors/pharmacology , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/classification , HIV-1/drug effects , HIV-1/genetics , Humans , Molecular Sequence Data , Peptide Fragments/pharmacology , Recombination, Genetic , Sequence Analysis, DNA
12.
J Gen Virol ; 86(Pt 7): 2047-2056, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15958684

ABSTRACT

Blood samples (n=544) from two different populations (Pygmies and Bantus) in Cameroon, West Africa, were analysed. Serological tests indicated that the anti-hepatitis C virus (HCV) prevalence in Bantus (20.3 %) was higher than that in Pygmies (2.3 %, P<0.0001), whereas the distribution of hepatitis B virus (HBV) serological markers was equally high in both populations: in total, 9.4, 17.3 and 86.8 % for HBsAg, anti-HBs and anti-HBc, respectively. HBV genotype A (HBV/A) and HBV/E were predominant (43.5 % each) in both populations, and HBV/D was found in a minority (13 %). The preS/S region was sequenced in nine cases (five HBV/A and four HBV/E) and the complete genome in six cases (four HBV/A and two HBV/E). Subsequent phylogenetic analysis revealed that the HBV/A strains were distinct from the subtypes (subgenotypes) described previously, Ae (A2) and Aa (A1), and in the preS/S region they clustered with previously reported sequences from Cameroon. Based on the nucleotide difference from Aa (A1) and Ae (A2), more than 4 % in the complete genome, the Cameroonian strains were suggested to represent a new subtype (subgenotype), designated HBV/Ac (A3). A high (3.9 %) nucleotide divergence in HBV/Ac (A3) strains suggested that the subtype (subgenotype) has a long natural history in the population of Cameroon. One of the HBV/Ac (A3) strains was found to be a recombinant with an HBV/E-specific sequence in the polymerase reverse transcriptase domain. Further cohort studies will be required to assess detailed epidemiological, virological and clinical characteristics of HBV/Ac (A3), as well as its recombinant form.


Subject(s)
Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B/ethnology , Hepatitis B/epidemiology , Recombination, Genetic , Adult , Base Sequence , Cameroon/epidemiology , Cameroon/ethnology , DNA, Viral/analysis , Ethnicity , Female , Genetic Variation , Genotype , Hepatitis B/virology , Hepatitis B virus/isolation & purification , Hepatitis C/epidemiology , Hepatitis C/ethnology , Hepatitis C/virology , Humans , Male , Middle Aged , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA
13.
Antivir Ther ; 10(2): 335-41, 2005.
Article in English | MEDLINE | ID: mdl-15865228

ABSTRACT

OBJECTIVE: To assess the effectiveness of generic anti-retroviral drugs in terms of survival and virological and immunological responses, as well as their tolerability and the emergence of viral resistance. METHODS: A total of 109 HIV-1-infected patients were enrolled in a prospective cohort study in Yaoundé, Cameroon. Available generic drugs were a fixed-dose combination (FDC) of zidovudine (ZDV) and lamivudine (3TC), an FDC of 3TC, stavudine (d4T) and nevirapine (NVP), and individual formulations of ZDV, 3TC and NVP. RESULTS: At baseline, the median CD4 cell count was 150/mm3 [interquartile range (IQR) 61-223] and median viral load was 5.4 log10 copies/ml (IQR 4.8-5.6); 78% of patients received ZDV/3TC/NVP and 22% received 3TC/d4T/NVP. Median follow-up was 16 months (IQR 11-23). The survival probability was high (0.92 at 12 months); plasma viral load declined by a median of 3.3 log10 copies/ml and 86.9% of the intention-to-treat population had viral load <400 copies/ml at 12 months; CD4 count had increased by a median of 106 cells/mm3 at 12 months; drug resistance rarely emerged (incidence rate 3.2 per 100 person-years); and the treatments were reasonably well-tolerated (incidence rate of severe adverse effects 7.8 per 100 person-years). CONCLUSION: Together with previous pharmacological and clinical studies, this prospective study suggests that these generic antiretroviral drugs can be used in developing countries.


Subject(s)
Anti-HIV Agents/therapeutic use , Drugs, Generic/therapeutic use , HIV Infections/drug therapy , HIV-1 , Lamivudine/therapeutic use , Nevirapine/therapeutic use , Stavudine/therapeutic use , Zidovudine/therapeutic use , Adult , Anti-HIV Agents/pharmacology , CD4 Lymphocyte Count , Cameroon , Cohort Studies , Drug Resistance, Viral , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Male , Prospective Studies , Treatment Outcome , Viral Load
14.
J Acquir Immune Defic Syndr ; 37(5): 1632-40, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15577422

ABSTRACT

The performance of 4 rapid and simple assays: Camstix-HIV 1+2 (Camdiagnostix, Yaounde, Cameroon); Determine HIV 1+2+0 (Abbott Laboratories, Tokyo, Japan); Genie II HIV-1/HIV-2 (Bio-Rad, Marnes la Coquette, France); ImmunoComb II HIV 1 & 2 BiSpot (Orgenics, Yavne, Israel); and 2 fourth-generation ELISAs: Enzygnost HIV Integral (Dade Behring, Marburg, Germany) and Genscreen plus HIV Ag-Ab (Bio-Rad, Marnes la Coquette, France) currently used in Cameroon to detect HIV infections were evaluated on a local serum panel. A total of 503 samples were collected, using the Camstix-HIV 1+2 assay. Overall, 280 samples were confirmed HIV positive, 181 were negative, and 42 were indeterminate. All positive samples belonged to group M: CRF02_AG (73.5%), A1 (7.1%), A2 (1.2%), G (4.7%), F2 (5.1%), D (1.6%), CRF11 (1.6%), CRF06 (1.2%), and CRF01_AE (1.6%). Sensitivity, specificity, test efficiency, and positive and negative predictive values were calculated both including and excluding indeterminate samples. Except for Genie II and ImmunoComb II (98.9 and 99.3%, respectively), sensitivities were 100% for the remaining 4 tests. Specificities, efficiencies, and positive predictive values of all assays were negatively affected by the addition of HIV-indeterminate samples in the calculations. These data show the importance of prior test evaluations on local serum panels and in field conditions before a national policy for HIV screening is decided on and stress also the need to use tests and algorithms that can reduce the high number of HIV-indeterminate results in Africa.


Subject(s)
AIDS Serodiagnosis/methods , Enzyme-Linked Immunosorbent Assay/methods , Genetic Variation , HIV Antibodies/blood , HIV Infections/diagnosis , HIV-1/classification , Amino Acid Sequence , Cameroon , HIV Envelope Protein gp41/chemistry , HIV Envelope Protein gp41/genetics , HIV-1/genetics , HIV-1/immunology , HIV-2/immunology , Humans , Molecular Sequence Data , Mutation , Predictive Value of Tests , Sensitivity and Specificity , Time Factors
15.
J Acquir Immune Defic Syndr ; 37(5): 1641-50, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15577423

ABSTRACT

To monitor the presence of genotypic HIV-1 variants circulating in eastern Cameroon, blood samples from 57 HIV-1-infected individuals attending 3 local health centers in the bordering rural villages with Central African Republic (CAR) were collected and analyzed phylogenetically. Out of the 40 HIV-1 strains with positive polymerase chain reaction (PCR) profile for both gag and env-C2V3,12 (30.0%) had discordant subtype or CRF designation: 2 subtype B/A (gag/env), 1 B/CRF01, 2 B/CRF02, 1 CRF01/CRF01.A, 2 CRF11/CRF01, 1 CRF13/A, 1 CRF13/CRF01, 1 CRF13/CRF11, and 1 G/U (unclassified). Twenty-eight strains (70.0%) had concordant subtypes or CRF designation between gag and env: 27 subtype A and 1 F2. Out of the remaining 17HIV-1 strains negative for PCR with the env-C2V3 primers used, 10 (58.8%) had discordant subtype or CRF, and 7 (41.2%) had concordant one based on gag/pol/env-gp41 analysis. Altogether, a high proportion (22/57, 38.6%) of the isolates were found to be recombinant strains. In addition, an emergence of new forms of HIV-1 strains, such as subtype B/A (gag/env), B/CRF01 and B/CRF02, was identified. The epidemiologic pattern of HIV-1 in eastern Cameroon, relatively low and high prevalence of CRF02 and CRF11, respectively, was more closely related to those of CAR and Chad than that of other regions of Cameroon, where CRF02 is the most predominant HIV-1 strain. These findings strongly suggest that this part of Cameroon is a potential hotspot of HIV-1 recombination, with a likelihood of an active generation of new forms of HIV-1 variants, though epidemiologic significance of new HIV-1 forms is unknown.


Subject(s)
Genetic Variation , HIV Infections/epidemiology , HIV-1/classification , Recombination, Genetic , Rural Population , Adolescent , Adult , Amino Acid Sequence , Cameroon/epidemiology , Central African Republic/epidemiology , Chad/epidemiology , Child, Preschool , Female , HIV Infections/virology , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Sequence Analysis, DNA , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolism
16.
Virology ; 326(2): 329-39, 2004 Sep 01.
Article in English | MEDLINE | ID: mdl-15321704

ABSTRACT

In this report, we describe the construction and characterization of the first full-length infectious molecular clone from the Cameroonian HIV-1 group O primary isolate MVP8913. Virus obtained after transfection of the proviral clone pCMO2.3 replicated to levels comparable to its parental isolate in the human T-cell line PM-1, although replication was reduced by fivefold in peripheral blood mononuclear cells (PBMC) and was barely detectable in primary monocyte-derived macrophages (MDM). Phylogenetic analysis of the complete proviral sequence revealed a closer relationship to ANT70 than to MVP5180, the two prototypic group O primary isolates. All reading frames for structural and accessory genes were open except for vpr that contained an in-frame stop codon. In the nef gene, a mutation disrupting the functionally important myristoylation signal was observed. Repairing the defect in nef enhanced replication in PBMC and MDM, although repairing the vpr defect only affected replication in MDM, consistent with the known phenotypes of vpr and nef mutants in HIV-1 group M viruses. Repairing both vpr and nef showed an additive effect, but the resulting virus was still impaired compared to the parental isolate. This defect was overcome when the gag-pol coding region was exchanged for that from another O-type isolate giving rise to the proviral clone pCMO2.5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses.


Subject(s)
Genes, nef , Genes, vpr , HIV-1/genetics , Cells, Cultured , Cloning, Molecular , Gene Deletion , Gene Products, gag/genetics , Gene Products, pol/genetics , HIV Infections/virology , HIV-1/pathogenicity , Humans , Molecular Sequence Data , Phylogeny , Virulence/genetics , Virus Replication
17.
Lancet ; 364(9428): 29-34, 2004.
Article in English | MEDLINE | ID: mdl-15234853

ABSTRACT

BACKGROUND: Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine. METHODS: 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis. FINDINGS: At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine. INTERPRETATION: Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.


Subject(s)
Anti-Retroviral Agents/administration & dosage , Developing Countries , Drugs, Generic/administration & dosage , HIV Infections/drug therapy , HIV-1 , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Anti-Retroviral Agents/adverse effects , CD4 Lymphocyte Count , Cameroon , Disease Progression , Drug Combinations , Drugs, Generic/adverse effects , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/isolation & purification , Humans , Lamivudine/administration & dosage , Lamivudine/adverse effects , Male , Nevirapine/administration & dosage , Nevirapine/adverse effects , Reverse Transcriptase Inhibitors/administration & dosage , Stavudine/administration & dosage , Stavudine/adverse effects , Viral Load
18.
J Clin Microbiol ; 42(6): 2711-7, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15184457

ABSTRACT

The Celera Diagnostics ViroSeq HIV-1 Genotyping System is a Food and Drug Administration-cleared, integrated system for sequence-based analysis of drug resistance mutations in subtype B human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT). We evaluated the performance of this system for the analysis of diverse HIV-1 strains. Plasma samples were obtained from 126 individuals from Uganda, Cameroon, South Africa, Argentina, Brazil, and Thailand with viral loads ranging from 2.92 to >6.0 log(10) copies/ml. HIV-1 genotyping was performed with the ViroSeq system. HIV-1 subtyping was performed by using phylogenetic methods. PCR products suitable for sequencing were obtained for 125 (99%) of the 126 samples. Genotypes including protease (amino acids 1 to 99) and RT (amino acids 1 to 321) were obtained for 124 (98%) of the samples. Full bidirectional sequence data were obtained for 95 of those samples. The sequences were categorized into the following subtypes: A1/A2 (16 samples), B (12 samples), C (13 samples), D (11 samples), CRF01_AE (9 samples), F/F2 (9 samples), G (7 samples), CRF02_AG (32 samples), H (1 sample), and intersubtype recombinant (14 samples). The performances of the individual sequencing primers were examined. Genotyping of duplicate samples in a second laboratory was successful for 124 of the 126 samples. The identity level for the sequence data from two laboratories ranged from 98 to 100% (median, 99.8%). The ViroSeq system performs well for the analysis of plasma samples with diverse non-B subtypes. The availability of this genotyping system should facilitate studies of HIV-1 drug resistance in non-subtype B strains of HIV-1.


Subject(s)
HIV-1/classification , Base Sequence , DNA Primers , Drug Resistance, Viral , Genotype , HIV-1/genetics , Humans , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Reproducibility of Results , Sequence Analysis, DNA , Viral Load
19.
AIDS Res Hum Retroviruses ; 20(1): 105-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15008125

ABSTRACT

To describe the presence of protease inhibitor (PI) resistance-associated mutations and subtype distribution in drug-naive villagers of six provinces of Cameroon, we sequenced the protease (PR) gene (297 bp) of 128 viruses. Secondary PI resistance-associated mutations were identified at five sites: L10I/V (16%), K20R (8%), M36I (98%), L63P (13%), and V77I (6%). No primary mutation in the PR was identified. Of the 128 specimens analyzed, subtypes A (11%), C(2%), D (6%), F2 (3%), G (6%), H (0.8%), J (6%), and CRF02_AG (60%) were identified. The mutations identified were not characteristic to any particular subtype. The absence of primary mutations, in addition to the few secondary mutations, gives good perspectives for PI treatment interventions in these rural areas.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Protease/genetics , HIV-1/enzymology , Mutation , Rural Population , Adolescent , Adult , Aged , Anti-HIV Agents/pharmacology , Cameroon/epidemiology , Drug Resistance, Viral , Female , HIV Infections/epidemiology , HIV Infections/virology , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , HIV-1/classification , HIV-1/drug effects , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Sequence Analysis, DNA
20.
AIDS Res Hum Retroviruses ; 20(1): 55-65, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15000699

ABSTRACT

Studies of HIV-1 immunological relatedness have revealed that genetic diversity does not parallel antigenic diversity and have recently shown that HIV-1 strains from different geographic regions from around the world can be grouped into a small number of immunologically defined groups (immunotypes). Previously, the binding patterns of 28 monoclonal antibodies (mAbs) (specific for V3 and C5 of gp120 and cluster I of gp41) with 26 HIV-1 virions obtained globally were determined in a virus binding assay. Analysis of the binding patterns of these 728 mAb/virus combinations now reveals that a particular subset containing six of the 28 mAbs can correctly immunotype 24 of the 26 isolates (92%) into three immunotypes. Like the original panel of mAbs, the subset of six mAbs identified was directed against epitopes in the V3 and C5 regions of gp 120 as well as cluster I of gp41. The binding patterns ("profiles") of these six mAbs with 24 additional HIV-1 virions from Cameroon confirmed that epitopes in V3 and C5 of gp120 and cluster I of gp41 are well exposed on these viruses. Multivariate analysis of the binding patterns of these six mAbs with all 50 viruses (26 obtained globally and 24 obtained from Cameroon) indicates that the viruses from Cameroon have binding profiles similar to viruses from the rest of the world and can be classified into the same three immunotypes that were previously described. This study suggests that a vaccine against HIV-1 need not be based on geographic origin of the virus or on clade, but may better be based on antigenic properties that classify the plethora of different HIV-1 viruses into immunologically defined groups.


Subject(s)
Antibodies, Monoclonal/immunology , HIV Antibodies/immunology , HIV-1/classification , HIV-1/immunology , Cameroon , Cluster Analysis , HIV Envelope Protein gp120/immunology , HIV Envelope Protein gp41/immunology , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , Humans
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